Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures

NARCIS (Netherlands)

C. Monnereau; S. Vogelezang; C.J. Kruithof (Claudia); V.W.V. Jaddoe (Vincent); J.F. Felix (Janine)

2016-01-01

textabstractBackground: Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. Methods:

Adipose-derived stem cells for treatment of chronic ulcers

DEFF Research Database (Denmark)

Holm, Jens Selch; Toyserkani, Navid Mohamadpour; Sorensen, Jens Ahm

2018-01-01

Chronic ulcers remain a difficult challenge in healthcare systems. While treatment options are limited, stem cells may be a novel alternative. Adipose-derived stem cells (ADSC) have become increasingly popular compared with bone marrow-derived stem cells as they are far easier to harvest...

Therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis

International Nuclear Information System (INIS)

Chang Pengyu; Cui Shuang; Luo Jinghua; Qu Chao; Jiang Xin; Qu Yaqin; Dong Lihua

2014-01-01

Objective: To evaluate the therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis. Methods: A total of 52 male Sprague-Dawley rats were used in the present study. Herein, 46 rats were randomly selected and irradiated with a dose of 15 Gy at their abdomens. Two hours post-irradiation, 23 rats were randomly selected and infused intraperitoneally with adipose-derived mesenchymal stem cells in passage 6 from young-female donor. The other 23 rats were intraperitoneally infused with PBS. The rest 6 rats were set as normal control. During the first 10 days post-irradiation, peripheral blood-samples from irradiated rats were harvested for testing the levels of IL-10 in serum using ELISA assay. Additionally, after isolating the thymic cells and peripheral blood mononuclear cells, the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in thymus and peripheral blood were tested by flow-cytometry. Finally, infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were analyzed by H&E staining and Masson Trichrome staining, respectively. Based on the MPO-immunohistochemistry staining, the type of infiltrated cells was identified. The Kaplan-Meier method was used for analyzing the survival rate of irradiated rats. Results: During a period of 30 days post-irradiation, the irradiated rats receiving adipose-derived mesenchymal stem cells survived longer than those receiving PBS (t = 4.53, P < 0.05). Compared to the irradiated rats with PBS-treatment, adipose-derived mesenchymal stem cells could elevate the level of IL-10 in serum (7 d: t = 13.93, P < 0.05) and increase the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in both peripheral blood (3.5 d: t = 7.72, 7 d: t = 11.11, 10 d: t = 6.99, P < 0.05) and thymus (7 d: t = 16.17, 10 d: t = 12.12, P < 0.05). Moreover, infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were mitigated by adipose-derived

Virally and physically transgenized equine adipose-derived stromal cells as a cargo for paracrine secreted factors

Directory of Open Access Journals (Sweden)

Cavirani Sandro

2010-09-01

Full Text Available Abstract Background Adipose-Derived Stromal Cells have been shown to have multiple lineage differentiation properties and to be suitable for tissues regeneration in many degenerative processes. Their use has been proposed for the therapy of joint diseases and tendon injuries in the horse. In the present report the genetic manipulation of Equine Adipose-Derived Stromal Cells has been investigated. Results Equine Adipose-Derived Stromal Cells were successfully virally transduced as well as transiently and stably transfected with appropriate parameters, without detrimental effect on their differentiation properties. Moreover, green fluorescent protein alone, fused to neo gene, or co-expressed as bi-cistronic reporter constructs, driven by viral and house-keeping gene promoters, were tested. The better expressed cassette was employed to stably transfect Adipose-Derived Stromal Cells for cell therapy purposes. Stably transfected Equine Adipose-Derived Stromal Cells with a heterologous secreted viral antigen were able to immunize horses upon injection into the lateral wall of the neck. Conclusion This study provides the methods to successfully transgenize Adipose-Derived Stromal Cells both by lentiviral vector and by transfection using optimized constructs with suitable promoters and reporter genes. In conclusion these findings provide a working platform for the delivery of potentially therapeutic proteins to the site of cells injection via transgenized Equine Adipose-Derived Stromal Cells.

Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

Science.gov (United States)

Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

2017-09-01

Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Human adipose-derived stem cells: definition, isolation, tissue-engineering applications.

Science.gov (United States)

Nae, S; Bordeianu, I; Stăncioiu, A T; Antohi, N

2013-01-01

Recent researches have demonstrated that the most effective repair system of the body is represented by stem cells - unspecialized cells, capable of self-renewal through successive mitoses, which have also the ability to transform into different cell types through differentiation. The discovery of adult stem cells represented an important step in regenerative medicine because they no longer raises ethical or legal issues and are more accessible. Only in 2002, stem cells isolated from adipose tissue were described as multipotent stem cells. Adipose tissue stem cells benefits in tissue engineering and regenerative medicine are numerous. Development of adipose tissue engineering techniques offers a great potential in surpassing the existing limits faced by the classical approaches used in plastic and reconstructive surgery. Adipose tissue engineering clinical applications are wide and varied, including reconstructive, corrective and cosmetic procedures. Nowadays, adipose tissue engineering is a fast developing field, both in terms of fundamental researches and medical applications, addressing issues related to current clinical pathology or trauma management of soft tissue injuries in different body locations.

Myocardial regeneration potential of adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

2010-10-22

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

Myocardial regeneration potential of adipose tissue-derived stem cells

International Nuclear Information System (INIS)

Bai, Xiaowen; Alt, Eckhard

2010-01-01

Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation.

Science.gov (United States)

Hamid, Adila A; Idrus, Ruszymah Bt Hj; Saim, Aminuddin Bin; Sathappan, Somasumdaram; Chua, Kien-Hui

2012-01-01

Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction. Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction. Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN) was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction. Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adipose-derived stem cells was most prominent after one week of chondrogenic induction.

Senescence and quiescence in adipose-derived stromal cells

DEFF Research Database (Denmark)

Søndergaard, Rebekka Harary; Follin, Bjarke; Lund, Lisbeth Drozd

2017-01-01

Background aims. Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine...

Adult adiposity linked to relationship hostility for low cortisol reactors

OpenAIRE

Slep, Amy; Lorber, Michael; Thorson, Katherine; Heyman, Richard

2017-01-01

Past research on the relation between hostility in intimate relationships and adiposity has yielded mixed findings. The present study investigated whether the association between relationship hostility and adiposity is moderated by people’s biological reactions to couple conflict. Cohabiting adult couples (N = 117 couples) engaged in two conflict interactions, before and after which salivary cortisol levels were measured. Results revealed an association between relationship hostility and adip...

Morphological, molecular and functional differences of adult bone marrow- and adipose-derived stem cells isolated from rats of different ages

International Nuclear Information System (INIS)

Mantovani, Cristina; Raimondo, Stefania; Haneef, Maryam S.; Geuna, Stefano; Terenghi, Giorgio; Shawcross, Susan G.; Wiberg, Mikael

2012-01-01

Adult mesenchymal stem cells have self-renewal and multiple differentiation potentials, and play important roles in regenerative medicine. However, their use may be limited by senescence or age of the donor, leading to changes in stem cell functionality. We investigated morphological, molecular and functional differences between bone marrow-derived (MSC) and adipose-derived (ASC) stem cells isolated from neonatal, young and old rats compared to Schwann cells from the same animals. Immunocytochemistry, RT-PCR, proliferation assays, western blotting and transmission electron microscopy were used to investigate expression of senescence markers. Undifferentiated and differentiated ASC and MSC from animals of different ages expressed Notch-2 at similar levels; protein-38 and protein-53 were present in all groups of cells with a trend towards increased levels in cells from older animals compared to those from neonatal and young rats. Following co-culture with adult neuronal cells, dMSC and dASC from animals of all ages elicited robust neurite outgrowth. Mitotracker ® staining was consistent with ultrastructural changes seen in the mitochondria of cells from old rats, indicative of senescence. In conclusion, this study showed that although the cells from aged animals expressed markers of senescence, aged MSC and ASC differentiated into SC-like cells still retain potential to support axon regeneration. -- Highlights: ► Aged MSC and ASC differentiated into Schwann-like cells support axon regeneration. ► p53 expression does not appreciably influence the biology of Schwann or stem cells. ► Notch 2 expression was similar in cells derived from animals of different ages. ► Proliferation rates of dMSC varied little over time or with animal age.

In vitro chondrogenic differentiation of human adipose-derived stem cells with silk scaffolds

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Hyeon Joo Kim

2012-12-01

Full Text Available Human adipose-derived stem cells have shown chondrogenic differentiation potential in cartilage tissue engineering in combination with natural and synthetic biomaterials. In the present study, we hypothesized that porous aqueous-derived silk protein scaffolds would be suitable for chondrogenic differentiation of human adipose-derived stem cells. Human adipose-derived stem cells were cultured up to 6 weeks, and cell proliferation and chondrogenic differentiation were investigated and compared with those in conventional micromass culture. Cell proliferation, glycosaminoglycan, and collagen levels in aqueous-derived silk scaffolds were significantly higher than in micromass culture. Transcript levels of SOX9 and type II collagen were also upregulated in the cell–silk constructs at 6 weeks. Histological examination revealed that the pores of the silk scaffolds were filled with cells uniformly distributed. In addition, chondrocyte-specific lacunae formation was evident and distributed in the both groups. The results suggest the biodegradable and biocompatible three-dimensional aqueous-derived silk scaffolds provided an improved environment for chondrogenic differentiation compared to micromass culture.

Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial)

DEFF Research Database (Denmark)

Qayyum, Abbas Ali; Haack-Sørensen, Mandana; Mathiasen, Anders Bruun

2012-01-01

Adipose tissue represents an abundant, accessible source of multipotent adipose-derived stromal cells (ADSCs). Animal studies have suggested that ADSCs have the potential to differentiate in vivo into endothelial cells and cardiomyocytes. This makes ADSCs a promising new cell source...... for regenerative therapy to replace injured tissue by creating new blood vessels and cardiomyocytes in patients with chronic ischemic heart disease. The aim of this special report is to review the present preclinical data leading to clinical stem cell therapy using ADSCs in patients with ischemic heart disease....... In addition, we give an introduction to the first-in-man clinical trial, MyStromalCell Trial, which is a prospective, randomized, double-blind, placebo-controlled study using culture-expanded ADSCs obtained from adipose-derived cells from abdominal adipose tissue and stimulated with VEGF-A(165) the week...

Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures

OpenAIRE

Monnereau, Claire; Vogelezang, Suzanne; Kruithof, Claudia J.; Jaddoe, Vincent W. V.; Felix, Janine F.

2016-01-01

Background Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. Methods We used data from a population-based prospective cohort study among 3,975 children with a mean age of 6?years. Genetic risk scores were constructed based on the 97 SNPs associated with adult BMI previously identi...

Analysis of in vitro secretion profiles from adipose-derived cell populations

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Blaber Sinead P

2012-08-01

Full Text Available Abstract Background Adipose tissue is an attractive source of cells for therapeutic purposes because of the ease of harvest and the high frequency of mesenchymal stem cells (MSCs. Whilst it is clear that MSCs have significant therapeutic potential via their ability to secrete immuno-modulatory and trophic cytokines, the therapeutic use of mixed cell populations from the adipose stromal vascular fraction (SVF is becoming increasingly common. Methods In this study we have measured a panel of 27 cytokines and growth factors secreted by various combinations of human adipose-derived cell populations. These were 1. co-culture of freshly isolated SVF with adipocytes, 2. freshly isolated SVF cultured alone, 3. freshly isolated adipocytes alone and 4. adherent adipose-derived mesenchymal stem cells (ADSCs at passage 2. In addition, we produced an ‘in silico’ dataset by combining the individual secretion profiles obtained from culturing the SVF with that of the adipocytes. This was compared to the secretion profile of co-cultured SVF and adipocytes. Two-tailed t-tests were performed on the secretion profiles obtained from the SVF, adipocytes, ADSCs and the ‘in silico’ dataset and compared to the secretion profiles obtained from the co-culture of the SVF with adipocytes. A p-value of  Results A co-culture of SVF and adipocytes results in a distinct secretion profile when compared to all other adipose-derived cell populations studied. This illustrates that cellular crosstalk during co-culture of the SVF with adipocytes modulates the production of cytokines by one or more cell types. No biologically relevant differences were detected in the proteomes of SVF cultured alone or co-cultured with adipocytes. Conclusions The use of mixed adipose cell populations does not appear to induce cellular stress and results in enhanced secretion profiles. Given the importance of secreted cytokines in cell therapy, the use of a mixed cell population such as the

Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions

Energy Technology Data Exchange (ETDEWEB)

Guneta, Vipra [Division of Materials Technology, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Tan, Nguan Soon [School of Biological Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); KK Research Centre, KK Women' s and Children Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore); Institute of Molecular and Cell Biology, Agency for Science Technology & Research - A*STAR, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore); Chan, Soon Kiat Jeremy [School of Biological Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Tanavde, Vivek [Bioinformatics Institute, Agency for Science Technology & Research - A*STAR, 30 Biopolis Street, Matrix, Singapore 138671 (Singapore); Lim, Thiam Chye [Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, National University Hospital (NUH) and National University of Singapore (NUS), Kent Ridge Wing, Singapore 119074 (Singapore); Wong, Thien Chong Marcus [Plastic, Reconstructive and Aesthetic Surgery Section, Tan Tock Seng Hospital (TTSH), 11, Jalan Tan Tock Seng, Singapore 308433 (Singapore); Choong, Cleo, E-mail: cleochoong@ntu.edu.sg [Division of Materials Technology, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); KK Research Centre, KK Women' s and Children Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore)

2016-11-01

Mesenchymal stem cells (MSCs), which were first isolated from the bone marrow, are now being extracted from various other tissues in the body, including the adipose tissue. The current study presents systematic evidence of how the adipose tissue-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (Bm-MSCs) behave when cultured in specific pro-adipogenic microenvironments. The cells were first characterized and identified as MSCs in terms of their morphology, phenotypic expression, self-renewal capabilities and multi-lineage potential. Subsequently, the proliferation and gene expression profiles of the cell populations cultured on two-dimensional (2D) adipose tissue extracellular matrix (ECM)-coated tissue culture plastic (TCP) and in three-dimensional (3D) AlgiMatrix® microenvironments were analyzed. Overall, it was found that adipogenesis was triggered in both cell populations due to the presence of adipose tissue ECM. However, in 3D microenvironments, ASCs and Bm-MSCs were predisposed to the adipogenic and osteogenic lineages respectively. Overall, findings from this study will contribute to ongoing efforts in adipose tissue engineering as well as provide new insights into the role of the ECM and cues provided by the immediate microenvironment for stem cell differentiation. - Highlights: • Native adipose tissue ECM coated on 2D TCP triggers adipogenesis in both ASCs and Bm-MSCs. • A 3D microenvironment with similar stiffness to adipose tissue induces adipogenic differentiation of ASCs. • ASCs cultured in 3D alginate scaffolds exhibit predisposition to adipogenesis. • Bm-MSCs cultured in 3D alginate scaffolds exhibit predisposition to osteogenesis. • The native microenvironment of the cells affects their differentiation behaviour in vitro.

Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions

International Nuclear Information System (INIS)

Guneta, Vipra; Tan, Nguan Soon; Chan, Soon Kiat Jeremy; Tanavde, Vivek; Lim, Thiam Chye; Wong, Thien Chong Marcus; Choong, Cleo

2016-01-01

Mesenchymal stem cells (MSCs), which were first isolated from the bone marrow, are now being extracted from various other tissues in the body, including the adipose tissue. The current study presents systematic evidence of how the adipose tissue-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (Bm-MSCs) behave when cultured in specific pro-adipogenic microenvironments. The cells were first characterized and identified as MSCs in terms of their morphology, phenotypic expression, self-renewal capabilities and multi-lineage potential. Subsequently, the proliferation and gene expression profiles of the cell populations cultured on two-dimensional (2D) adipose tissue extracellular matrix (ECM)-coated tissue culture plastic (TCP) and in three-dimensional (3D) AlgiMatrix® microenvironments were analyzed. Overall, it was found that adipogenesis was triggered in both cell populations due to the presence of adipose tissue ECM. However, in 3D microenvironments, ASCs and Bm-MSCs were predisposed to the adipogenic and osteogenic lineages respectively. Overall, findings from this study will contribute to ongoing efforts in adipose tissue engineering as well as provide new insights into the role of the ECM and cues provided by the immediate microenvironment for stem cell differentiation. - Highlights: • Native adipose tissue ECM coated on 2D TCP triggers adipogenesis in both ASCs and Bm-MSCs. • A 3D microenvironment with similar stiffness to adipose tissue induces adipogenic differentiation of ASCs. • ASCs cultured in 3D alginate scaffolds exhibit predisposition to adipogenesis. • Bm-MSCs cultured in 3D alginate scaffolds exhibit predisposition to osteogenesis. • The native microenvironment of the cells affects their differentiation behaviour in vitro.

Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation

Directory of Open Access Journals (Sweden)

Adila A Hamid

2012-01-01

Full Text Available OBJECTIVES: Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction. MATERIALS AND METHODS: Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction. RESULTS: Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction. CONCLUSION: Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adiposederived stem cells was most prominent after one week of chondrogenic induction.

Morphological, molecular and functional differences of adult bone marrow- and adipose-derived stem cells isolated from rats of different ages

Energy Technology Data Exchange (ETDEWEB)

Mantovani, Cristina [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Department of Integrative Medical Biology and Surgical and Perioperative Science, Umea University, Umea (Sweden); Department of Surgical and Perioperative Science, Umea University, Umea (Sweden); Raimondo, Stefania [Dipartimento di Scienze Cliniche e Biologiche, University of Turin (Italy); Haneef, Maryam S. [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Geuna, Stefano [Dipartimento di Scienze Cliniche e Biologiche, University of Turin (Italy); Terenghi, Giorgio [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Shawcross, Susan G., E-mail: sue.shawcross@manchester.ac.uk [Blond McIndoe Laboratories, School of Biomedicine, The University of Manchester, Room 3,106 Stopford Building, Oxford Road, Manchester M13 9PT, Academic Health Science Centre, Faculty of Medicine and Human Sciences (United Kingdom); Wiberg, Mikael [Department of Integrative Medical Biology and Surgical and Perioperative Science, Umea University, Umea (Sweden); Department of Surgical and Perioperative Science, Umea University, Umea (Sweden)

2012-10-01

Adult mesenchymal stem cells have self-renewal and multiple differentiation potentials, and play important roles in regenerative medicine. However, their use may be limited by senescence or age of the donor, leading to changes in stem cell functionality. We investigated morphological, molecular and functional differences between bone marrow-derived (MSC) and adipose-derived (ASC) stem cells isolated from neonatal, young and old rats compared to Schwann cells from the same animals. Immunocytochemistry, RT-PCR, proliferation assays, western blotting and transmission electron microscopy were used to investigate expression of senescence markers. Undifferentiated and differentiated ASC and MSC from animals of different ages expressed Notch-2 at similar levels; protein-38 and protein-53 were present in all groups of cells with a trend towards increased levels in cells from older animals compared to those from neonatal and young rats. Following co-culture with adult neuronal cells, dMSC and dASC from animals of all ages elicited robust neurite outgrowth. Mitotracker{sup Registered-Sign} staining was consistent with ultrastructural changes seen in the mitochondria of cells from old rats, indicative of senescence. In conclusion, this study showed that although the cells from aged animals expressed markers of senescence, aged MSC and ASC differentiated into SC-like cells still retain potential to support axon regeneration. -- Highlights: Black-Right-Pointing-Pointer Aged MSC and ASC differentiated into Schwann-like cells support axon regeneration. Black-Right-Pointing-Pointer p53 expression does not appreciably influence the biology of Schwann or stem cells. Black-Right-Pointing-Pointer Notch 2 expression was similar in cells derived from animals of different ages. Black-Right-Pointing-Pointer Proliferation rates of dMSC varied little over time or with animal age.

Human adipose-derived stromal/stem cell isolation, culture, and osteogenic differentiation.

Science.gov (United States)

Qureshi, Ammar T; Chen, Cong; Shah, Forum; Thomas-Porch, Caasy; Gimble, Jeffrey M; Hayes, Daniel J

2014-01-01

Annually, more than 200,000 elective liposuction procedures are performed in the United States and over a million worldwide. The ease of harvest and abundance make human adipose-derived stromal/stem cells (hASCs) isolated from lipoaspirates an attractive, readily available source of adult stem cells that have become increasingly popular for use in many studies. Here, we describe common methods for hASC culture, preservation, and osteogenic differentiation. We introduce methods of ceramic, polymer, and composite scaffold synthesis with a description of morphological, chemical, and mechanical characterization techniques. Techniques for scaffold loading are compared, and methods for determining cell loading efficiency and proliferation are described. Finally, we provide both qualitative and quantitative techniques for in vitro assessment of hASC osteogenic differentiation. © 2014 Elsevier Inc. All rights reserved.

One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation

International Nuclear Information System (INIS)

Yue Guiping; Du Lirui; Xia Tao; He Xianhui; Qiu Huan; Xu Lihui; Chen Xiaodong; Feng Shengqiu; Yang Zaiqing

2005-01-01

One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Science.gov (United States)

Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

2010-01-01

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Directory of Open Access Journals (Sweden)

Sadanori Akita

2010-01-01

Full Text Available Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

Culture of equine bone marrow mononuclear fraction and adipose tissue-derived stromal vascular fraction cells in different media

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Gesiane Ribeiro

2013-12-01

Full Text Available The objective of this study was to evaluate the culture of equine bone marrow mononuclear fraction and adipose tissue - derived stromal vascular fraction cells in two different cell culture media. Five adult horses were submitted to bone marrow aspiration from the sternum, and then from the adipose tissue of the gluteal region near the base of the tail. Mononuclear fraction and stromal vascular fraction were isolated from the samples and cultivated in DMEM medium supplemented with 10% fetal bovine serum or in AIM-V medium. The cultures were observed once a week with an inverted microscope, to perform a qualitative analysis of the morphology of the cells as well as the general appearance of the cell culture. Colony-forming units (CFU were counted on days 5, 15 and 25 of cell culture. During the first week of culture, differences were observed between the samples from the same source maintained in different culture media. The number of colonies was significantly higher in samples of bone marrow in relation to samples of adipose tissue.

Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity

OpenAIRE

Christou, Demetra D.; Pierce, Gary L.; Walker, Ashley E.; Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Meade, Thomas H.; English, Mark; Seals, Douglas R.

2012-01-01

Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18–79 years; body mass index (BMI), 16.4–42.2 kg/m2], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI...

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

Energy Technology Data Exchange (ETDEWEB)

Kasten, Annika; Siegmund, Birte J. [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany); Grüttner, Cordula [Micromod Partikeltechnologie GmbH, Warnemünde, D-18115 Rostock (Germany); Kühn, Jens-Peter [Department of Radiology and Neuroradiology, Greifswald University Medical Center, D-17475 Greifswald (Germany); Frerich, Bernhard, E-mail: bernhard.frerich@med.uni-rostock.de [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany)

2015-04-15

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation.

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

International Nuclear Information System (INIS)

Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

2015-01-01

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation

Childhood predictors of adult adiposity: findings from a longitudinal study.

Science.gov (United States)

McLeod, Geraldine Fh; Fergusson, David M; Horwood, L John; Boden, Joseph M; Carter, Frances A

2018-03-23

The increasing prevalence of overweight and obesity has become a key challenge for New Zealand. The purpose of the present study was to examine childhood risk factors for adult adiposity in a longitudinal birth cohort. Data were gathered from the Christchurch Health and Development Study (CHDS), a birth cohort of 1,265 children born in Christchurch in 1977. Associations were examined between socio-demographic background, perinatal factors, infant and child characteristics, family functioning/child maltreatment and adiposity at ages 30 and 35 years. Adiposity was assessed using body mass index scores. At ages 30 and 35, approximately one-third of cohort members were overweight and one-fifth were obese. Generalised estimating equation models showed that statistically significant (p<.05) predictors of later adiposity and overweight/obesity were: male gender, being born into a single-parent family, having parents with larger body size, higher early infant growth, limited or no breastfeeding, lower levels of cognitive ability and exposure to severe sexual abuse. Overweight and obesity was associated with social and family background, biological endowment, cognitive ability and childhood adversity factors. These findings may assist in the development of structured adiposity intervention programmes in conjunction with established community organisations specialising in child and family health.

Uninduced adipose-derived stem cells repair the defect of full-thickness hyaline cartilage.

Science.gov (United States)

Zhang, Hai-Ning; Li, Lei; Leng, Ping; Wang, Ying-Zhen; Lv, Cheng-Yu

2009-04-01

To testify the effect of the stem cells derived from the widely distributed fat tissue on repairing full-thickness hyaline cartilage defects. Adipose-derived stem cells (ADSCs) were derived from adipose tissue and cultured in vitro. Twenty-seven New Zealand white rabbits were divided into three groups randomly. The cultured ADSCs mixed with calcium alginate gel were used to fill the full-thickness hyaline cartilage defects created at the patellafemoral joint, and the defects repaired with gel or without treatment served as control groups. After 4, 8 and 12 weeks, the reconstructed tissue was evaluated macroscopically and microscopically. Histological analysis and qualitative scoring were also performed to detect the outcome. Full thickness hyaline cartilage defects were repaired completely with ADSCs-derived tissue. The result was better in ADSCs group than the control ones. The microstructure of reconstructed tissue with ADSCs was similar to that of hyaline cartilage and contained more cells and regular matrix fibers, being better than other groups. Plenty of collagen fibers around cells could be seen under transmission electron microscopy. Statistical analysis revealed a significant difference in comparison with other groups at each time point (t equal to 4.360, P less than 0.01). These results indicate that stem cells derived from mature adipose without induction possess the ability to repair cartilage defects.

Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT).

Science.gov (United States)

Bourin, Philippe; Bunnell, Bruce A; Casteilla, Louis; Dominici, Massimo; Katz, Adam J; March, Keith L; Redl, Heinz; Rubin, J Peter; Yoshimura, Kotaro; Gimble, Jeffrey M

2013-06-01

Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However, a characterization of the population of adipose-derived stromal and stem cells (ASCs) with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeutics and International Society for Cellular Therapy, this paper sets out to establish minimal definitions of stromal cells both as uncultured stromal vascular fraction (SVF) and as an adherent stromal/stem cells population. Phenotypic and functional criteria for the identification of adipose-derived cells were drawn from the literature. In the SVF, cells are identified phenotypically by the following markers: CD45-CD235a-CD31-CD34+. Added value may be provided by both a viability marker and the following surface antigens: CD13, CD73, CD90 and CD105. The fibroblastoid colony-forming unit assay permits the evaluation of progenitor frequency in the SVF population. In culture, ASCs retain markers in common with other mesenchymal stromal/stem cells (MSCs), including CD90, CD73, CD105, and CD44 and remain negative for CD45 and CD31. They can be distinguished from bone-marrow-derived MSCs by their positivity for CD36 and negativity for CD106. The CFU-F assay is recommended to calculate population doublings capacity of ASCs. The adipocytic, chondroblastic and osteoblastic differentiation assays serve to complete the cell identification and potency assessment in conjunction with a quantitative evaluation of the differentiation either biochemically or by reverse transcription polymerase chain reaction. The goal of this paper is to provide initial guidance for the scientific community working with adipose-derived cells and to facilitate development of international standards based on reproducible parameters. Copyright © 2013 International Society for Cellular Therapy. All rights reserved.

Human adipose stem cell and ASC-derived cardiac progenitor cellular therapy improves outcomes in a murine model of myocardial infarction

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Davy PMC

2015-10-01

Full Text Available Philip MC Davy,1 Kevin D Lye,2,3 Juanita Mathews,1 Jesse B Owens,1 Alice Y Chow,1 Livingston Wong,2 Stefan Moisyadi,1 Richard C Allsopp1 1Institute for Biogenesis Research, 2John A. Burns School of Medicine, University of Hawaii at Mānoa, 3Tissue Genesis, Inc., Honolulu, HI, USA Background: Adipose tissue is an abundant and potent source of adult stem cells for transplant therapy. In this study, we present our findings on the potential application of adipose-derived stem cells (ASCs as well as induced cardiac-like progenitors (iCPs derived from ASCs for the treatment of myocardial infarction. Methods and results: Human bone marrow (BM-derived stem cells, ASCs, and iCPs generated from ASCs using three defined cardiac lineage transcription factors were assessed in an immune-compromised mouse myocardial infarction model. Analysis of iCP prior to transplant confirmed changes in gene and protein expression consistent with a cardiac phenotype. Endpoint analysis was performed 1 month posttransplant. Significantly increased endpoint fractional shortening, as well as reduction in the infarct area at risk, was observed in recipients of iCPs as compared to the other recipient cohorts. Both recipients of iCPs and ASCs presented higher myocardial capillary densities than either recipients of BM-derived stem cells or the control cohort. Furthermore, mice receiving iCPs had a significantly higher cardiac retention of transplanted cells than all other groups. Conclusion: Overall, iCPs generated from ASCs outperform BM-derived stem cells and ASCs in facilitating recovery from induced myocardial infarction in mice. Keywords: adipose stem cells, myocardial infarction, cellular reprogramming, cellular therapy, piggyBac, induced cardiac-like progenitors

Association of Childhood Economic Hardship with Adult Height and Adult Adiposity among Hispanics/Latinos. The HCHS/SOL Socio-Cultural Ancillary Study.

Science.gov (United States)

Isasi, Carmen R; Jung, Molly; Parrinello, Christina M; Kaplan, Robert C; Kim, Ryung; Crespo, Noe C; Gonzalez, Patricia; Gouskova, Natalia A; Penedo, Frank J; Perreira, Krista M; Perrino, Tatiana; Sotres-Alvarez, Daniela; Van Horn, Linda; Gallo, Linda C

2016-01-01

The study examined the association of childhood and current economic hardship with anthropometric indices in Hispanic/Latino adults, using data from the HCHS/SOL Socio-cultural ancillary study (N = 5,084), a community-based study of Hispanic/Latinos living in four urban areas (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA). Childhood economic hardship was defined as having experienced a period of time when one's family had trouble paying for basic needs (e.g., food, housing), and when this economic hardship occurred: between 0-12, 13-18 years old, or throughout both of those times. Current economic hardship was defined as experiencing trouble paying for basic needs during the past 12 months. Anthropometry included height, body mass index (BMI), waist circumference (WC), and percentage body fat (%BF). Complex survey linear regression models were used to test the associations of childhood economic hardship with adult anthropometric indices, adjusting for potential confounders (e.g., age, sex, Hispanic background). Childhood economic hardship varied by Hispanic background, place of birth, and adult socio-economic status. Childhood economic hardship during both periods, childhood and adolescence, was associated with shorter height. Childhood economic hardship was associated with greater adiposity among US born individuals only. Current economic hardship was significantly associated with all three measures of adiposity (BMI, WC, %BF). These findings suggest that previous periods of childhood economic hardship appear to influence adult height more than adiposity, whereas current economic hardship may be a better determinant of adult adiposity in Hispanics.

MicroRNA expression profiling in neurogenesis of adipose tissue ...

Indian Academy of Sciences (India)

Adipose tissue-derived stem cells (ADSCs) are one population of adult stem cells that can self ... Because of advantages in method and quantity of acquisition, ADSCs are gaining ...... miRNAs specifically related to neuron cell generation.

Birth weight and risk of adiposity among adult Inuit in Greenland.

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Pernille Falberg Rønn

Full Text Available OBJECTIVE: The Inuit population in Greenland has undergone rapid socioeconomic and nutritional changes simultaneously with an increasing prevalence of obesity. Therefore, the objective was to examine fetal programming as part of the aetiology of obesity among Inuit in Greenland by investigating the association between birth weight and measures of body composition and fat distribution in adulthood. METHODS: The study was based on cross-sectional data from a total of 1,473 adults aged 18-61 years in two population-based surveys conducted in Greenland between 1999-2001 and 2005-2010. Information on birth weight was collected from birth records. Adiposity was assessed by anthropometry, fat mass index (FMI, fat-free mass index (FFMI, and visceral (VAT and subcutaneous adipose tissue (SAT estimated by ultrasound. The associations to birth weight were analyzed using linear regression models and quadratic splines. Analyses were stratified by sex, and adjusted for age, birthplace, ancestry and family history of obesity. RESULTS: Spline analyses showed linear relations between birth weight and adult adiposity. In multiple regression analyses, birth weight was positively associated with BMI, waist circumference, FMI, FFMI and SAT with generally weaker associations among women compared to men. Birth weight was only associated with VAT after additional adjustment for waist circumference and appeared to be specific and inverse for men only. CONCLUSIONS: Higher birth weight among Inuit was associated with adiposity in adulthood. More studies are needed to explore a potential inverse association between birth size and VAT.

Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

DEFF Research Database (Denmark)

Knudsen, Jakob Grunnet

Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... of both liver and adipose tissue regulation in whole body metabolism has come in to focus and it has been shown that both tissues are subject to exercise training-induced adaptations. However, the contribution of endocrine factors to the regulation of exercise training-induced adaptations in liver...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...

The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells

NARCIS (Netherlands)

Hajmousa, Ghazaleh; Vogelaar, Pieter; Brouwer, Linda A.; Graaf, Adrianus Cornelis van der; Henning, Robert H.; Krenning, Guido

Encouraging advances in cell therapy research with adipose derived stem cells (ASC) require an effective short-term preservation method that provides time for quality control and transport of cells from their manufacturing facility to their clinical destination. Hypothermic storage of cells in their

Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing, E-mail: caijingmmm@hotmail.com; Wang, Zehua, E-mail: zehuawang@163.net

2015-09-10

Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs.

Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

International Nuclear Information System (INIS)

Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing; Wang, Zehua

2015-01-01

Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs

Assessment of Energy Metabolic Changes in Adipose Tissue-Derived Stem Cells

NARCIS (Netherlands)

Hajmousa, Ghazaleh; Harmsen, Martin C; Di Nardo, Paolo; Dhingra, Sanjiv; Singla, Dinender K.

2017-01-01

Adipose tissue-derived stem cells (ADSC) are promising candidates for therapeutic applications in cardiovascular regenerative medicine. By definition, the phenotype ADSCs, e.g., the ubiquitous secretion of growth factors, cytokines, and extracellular matrix components is not met in vivo, which

Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

Science.gov (United States)

He, Xiaoli; H'ng, Shiau-Chen; Leong, David T; Hutmacher, Dietmar W; Melendez, Alirio J

2010-08-01

High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

Autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

Energy Technology Data Exchange (ETDEWEB)

Kasubuchi, Y; Mino, M; Yoshioka, H; Kusunoki, T [Kyoto Prefectural Univ. of Medicine (Japan)

1979-10-01

The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status.

Association of Childhood Economic Hardship with Adult Height and Adult Adiposity among Hispanics/Latinos. The HCHS/SOL Socio-Cultural Ancillary Study.

Directory of Open Access Journals (Sweden)

Carmen R Isasi

Full Text Available The study examined the association of childhood and current economic hardship with anthropometric indices in Hispanic/Latino adults, using data from the HCHS/SOL Socio-cultural ancillary study (N = 5,084, a community-based study of Hispanic/Latinos living in four urban areas (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA. Childhood economic hardship was defined as having experienced a period of time when one's family had trouble paying for basic needs (e.g., food, housing, and when this economic hardship occurred: between 0-12, 13-18 years old, or throughout both of those times. Current economic hardship was defined as experiencing trouble paying for basic needs during the past 12 months. Anthropometry included height, body mass index (BMI, waist circumference (WC, and percentage body fat (%BF. Complex survey linear regression models were used to test the associations of childhood economic hardship with adult anthropometric indices, adjusting for potential confounders (e.g., age, sex, Hispanic background. Childhood economic hardship varied by Hispanic background, place of birth, and adult socio-economic status. Childhood economic hardship during both periods, childhood and adolescence, was associated with shorter height. Childhood economic hardship was associated with greater adiposity among US born individuals only. Current economic hardship was significantly associated with all three measures of adiposity (BMI, WC, %BF. These findings suggest that previous periods of childhood economic hardship appear to influence adult height more than adiposity, whereas current economic hardship may be a better determinant of adult adiposity in Hispanics.

Adipose-derived mesenchymal stem cells and regenerative medicine.

Science.gov (United States)

Konno, Masamitsu; Hamabe, Atsushi; Hasegawa, Shinichiro; Ogawa, Hisataka; Fukusumi, Takahito; Nishikawa, Shimpei; Ohta, Katsuya; Kano, Yoshihiro; Ozaki, Miyuki; Noguchi, Yuko; Sakai, Daisuke; Kudoh, Toshihiro; Kawamoto, Koichi; Eguchi, Hidetoshi; Satoh, Taroh; Tanemura, Masahiro; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

2013-04-01

Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Immunomodulatory Effects of Adipose-Derived Stem Cells: Fact or Fiction?

Directory of Open Access Journals (Sweden)

Angelo A. Leto Barone

2013-01-01

Full Text Available Adipose-derived stromal cells (ASCs are often referred to as adipose-derived stem cells due to their potential to undergo multilineage differentiation. Their promising role in tissue engineering and ability to modulate the immune system are the focus of extensive research. A number of clinical trials using ASCs are currently underway to better understand the role of such cell niche in enhancing or suppressing the immune response. If governable, such immunoregulatory role would find application in several conditions in which an immune response is present (i.e., autoimmune conditions or feared (i.e., solid organ or reconstructive transplantation. Although allogeneic ASCs have been shown to prevent acute GvHD in both preclinical and clinical studies, their potential warrants further investigation. Well-designed and standardized clinical trials are necessary to prove the role of ASCs in the treatment of immune disorders or prevention of tissue rejection. In this paper we analyze the current literature on the role of ASCs in immunomodulation in vitro and in vivo and discuss their potential in regulating the immune system in the context of transplantation.

Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow and white adipose tissue via Pdgfrα expression.

Science.gov (United States)

Miwa, Hiroyuki; Era, Takumi

2018-01-29

Mesenchymal stem cells (MSCs) are somatic stem cells that can be derived from adult bone marrow (BM) and white adipose tissue (WAT), and that display multipotency and self-renewal capacity. Although MSCs are essential for tissue formation and have already been used in clinical therapy, the origins and markers of these cells remain unknown. In this study, we first investigated the developmental process of MSCs in mouse embryos using the gene encoding platelet-derived growth factor receptor α ( Pdgfra ) as a marker. We then traced cells expressing Pdgfra and other genes (brachyury, Sox1 and Pmx1 ) in various mutant mouse embryos until the adult stage. This tracing of MSC origins and destinies indicates that embryonic MSCs emerge in waves and that almost all adult BM MSCs and WAT MSCs originate from mesoderm and embryonic Pdgfrα-positive cells. Furthermore, we demonstrate that adult Pdgfrα-positive cells are involved in some pathological conditions. © 2018. Published by The Company of Biologists Ltd.

Delivery of Adipose-Derived Stem Cells Attenuates Adipose Tissue Inflammation and Insulin Resistance in Obese Mice Through Remodeling Macrophage Phenotypes.

Science.gov (United States)

Shang, Qianwen; Bai, Yang; Wang, Guannan; Song, Qiang; Guo, Chun; Zhang, Lining; Wang, Qun

2015-09-01

Adipose-derived stem cells (ADSCs) have been used to control several autoimmune or inflammatory diseases due to immunosuppressive properties, but their role in obesity-associated inflammation remains unestablished. This study aims to evaluate the effects of ADSCs on obesity-induced white adipose tissue (WAT) inflammation and insulin resistance. We found that diet-induced obesity caused a remarkable reduction of ADSC fraction in mouse WAT. Delivery of lean mouse-derived ADSCs, which could successfully locate into WAT of obese mice, substantially improved insulin action and metabolic homeostasis of obese mice. ADSC treatment not only reduced adipocyte hypertrophy but also attenuated WAT inflammation by reducing crown-like structures of macrophages and tumor necrosis factor (TNF)-α secretion. Importantly, ADSC treatment remodeled the phenotypes of adipose-resident macrophages from proinflammatory M1 toward anti-inflammatory M2-like subtypes, as characterized by decreased MHC class II-expressing but increased interleukin (IL)-10-producing macrophages together with low expression of TNF-α and IL-12. Coculture of ADSCs through the transwell or conditional medium with induced M1 macrophages also reproduced the phenotypic switch toward M2-like macrophages, which was substantiated by elevated arginase 1, declined inducible nitric oxide synthase, inhibition of NF-κB activity, and activation of STAT3/STAT6. Taken together, our data support that ADSC supplement in obese mice could sustain IL-10-producing M2-like macrophages in WAT through paracrine action, thereby suggesting the crucial role of ADSCs in resolving WAT inflammation, maintaining adipose homeostasis, and proposing a potential ADSC-based approach for the treatment of obesity-related diseases.

An autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

International Nuclear Information System (INIS)

Kasubuchi, Yasuo; Mino, Masahiro; Yoshioka, Hiroshi; Kusunoki, Tomoichi

1979-01-01

The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status. (author)

[EVALUATION OF THE BODY ADIPOSITY INDEX IN PREDICTING PERCENTAGE BODY FAT AMONG COLOMBIAN ADULTS].

Science.gov (United States)

González-Ruíz, Katherine; Correa-Bautista, Jorge Enrique; Ramírez-Vélez, Robinson

2015-07-01

the body adiposity index (BAI) is a new simplistic method for predicting body fat percentage (BF%) via a simple equation of hip circumference to height. Up to now, few studies have evaluated the performance of BAI in determining excess fat in Colombians. The aim of this study was to evaluate the usefulness of BAI as a predictor of body fat in among Colombian adults. cross-sectional study carried out in a sample of 204 male belonging to the education sector from Bogotá, Colombia. BAI was calculated based on the equation reported in the Bergman et al. %BF determined by tetrapolar bioimpedance analysis (BIA) was used as the reference measure of adiposity. Bland-Altman analysis was used to assess the agreement between the two methods: BAI and BIA. Associations between anthropometric measures of adiposity were investigated by Pearson correlation analysis. in general pupulation, the BAI overestimates %BF (mean difference: 12.5 % [95%CI = -4.04 % to -21.02 %]), mainly at lower levels of adiposity (mean difference: 10.2 ± 3.3). Significant correlations were found between BAI and all measurements, being the strongest-moderate correlation with %BF (r = 0.777, p Colombian adults and has a tendency to provide overestimated values as BF% decreases. Therefore, this method can be a useful tool to predict %BF in Colombian adults, although it has some limitations. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

[Human brown adipose tissue].

Science.gov (United States)

Virtanen, Kirsi A; Nuutila, Pirjo

2015-01-01

Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

Why are there race/ethnic differences in adult body mass index–adiposity relationships? A quantitative critical review

Science.gov (United States)

Heymsfield, S. B.; Peterson, C. M.; Thomas, D. M.; Heo, M.; Schuna, J. M.

2016-01-01

Summary Body mass index (BMI) is now the most widely used measure of adiposity on a global scale. Nevertheless, intense discussion centers on the appropriateness of BMI as a phenotypic marker of adiposity across populations differing in race and ethnicity. BMI-adiposity relations appear to vary significantly across race/ethnic groups, but a collective critical analysis of these effects establishing their magnitude and underlying body shape/composition basis is lacking. Accordingly, we systematically review the magnitude of these race-ethnic differences across non-Hispanic (NH) white, NH black and Mexican American adults, their anatomic body composition basis and potential biologically linked mechanisms, using both earlier publications and new analyses from the US National Health and Nutrition Examination Survey. Our collective observations provide a new framework for critically evaluating the quantitative relations between BMI and adiposity across groups differing in race and ethnicity; reveal new insights into BMI as a measure of adiposity across the adult age-span; identify knowledge gaps that can form the basis of future research and create a quantitative foundation for developing BMI-related public health recommendations. PMID:26663309

Why are there race/ethnic differences in adult body mass index-adiposity relationships? A quantitative critical review.

Science.gov (United States)

Heymsfield, S B; Peterson, C M; Thomas, D M; Heo, M; Schuna, J M

2016-03-01

Body mass index (BMI) is now the most widely used measure of adiposity on a global scale. Nevertheless, intense discussion centers on the appropriateness of BMI as a phenotypic marker of adiposity across populations differing in race and ethnicity. BMI-adiposity relations appear to vary significantly across race/ethnic groups, but a collective critical analysis of these effects establishing their magnitude and underlying body shape/composition basis is lacking. Accordingly, we systematically review the magnitude of these race-ethnic differences across non-Hispanic (NH) white, NH black and Mexican American adults, their anatomic body composition basis and potential biologically linked mechanisms, using both earlier publications and new analyses from the US National Health and Nutrition Examination Survey. Our collective observations provide a new framework for critically evaluating the quantitative relations between BMI and adiposity across groups differing in race and ethnicity; reveal new insights into BMI as a measure of adiposity across the adult age-span; identify knowledge gaps that can form the basis of future research and create a quantitative foundation for developing BMI-related public health recommendations. © 2015 World Obesity.

Android Adiposity and Lack of Moderate and Vigorous Physical Activity Are Associated With Insulin Resistance and Diabetes in Aging Adults.

Science.gov (United States)

Peterson, Mark D; Al Snih, Soham; Serra-Rexach, José A; Burant, Charles

2015-08-01

Physical inactivity and excess adiposity are thought to be interdependent "lifestyle" factors and thus, many older adults are at exaggerated risk for preventable diseases. The purposes of this study were to determine the degree of discordance between body mass index (BMI) and adiposity among adults older than 50 years, and to determine the extent to which direct measures of adiposity, and objectively measured sedentary behavior (SB) and physical activity (PA) are associated with insulin resistance (IR) or diabetes. A population representative sample of 2,816 individuals, aged 50-85 years, was included from the combined 2003-2006 National Health and Nutrition Examination Survey (NHANES) datasets. BMI, percent body fat (%BF) and android adiposity as determined by dual energy x-ray absorptiometry, objectively measured SB and PA, established markers of cardiometabolic risk, IR, and type 2 diabetes were analyzed. Approximately 50% of the men and 64% of the women who were normal weight according to BMI had excessive %BF. Adults with the least SB and greatest moderate and vigorous PA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest activity had highest risk. Greater android adiposity stores were robustly associated with IR or diabetes in all adults, independent of SB and activity. Among men, less moderate-to-vigorous PA was associated with IR or diabetes; whereas among women, less lifestyle moderate activity was associated with IR or diabetes. Android adiposity and low moderate and vigorous PA are the strongest predictors of IR or diabetes among aging adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

OpenAIRE

Peixoto, T.C.; Moura, E.G.; Oliveira, E.; Younes-Rapozo, V.; Soares, P.N.; Rodrigues, V.S.T.; Santos, T.R.; Peixoto-Silva, N.; Carvalho, J.C.; Calvino, C.; Conceição, E.P.S.; Guarda, D.S.; Claudio-Neto, S.; Manhães, A.C.; Lisboa, P.C.

2018-01-01

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower ...

A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes without Growth Factor Stimulation

Science.gov (United States)

2011-01-01

A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes Without Growth Factor Stimulation...Ph.D.3 This work describes the differentiation of adipose-derived mesenchymal stem cells (ASC) in a composite hy- drogel for use as a vascularized...tissue from a single population of ASC. This work underscores the importance of the extracellular matrix in controlling stem cell phenotype. It is our

Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults.

Science.gov (United States)

Pereira, Rocio I; Low Wang, Cecilia C; Wolfe, Pamela; Havranek, Edward P; Long, Carlin S; Bessesen, Daniel H

2015-12-22

Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R² = 0.42, p diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors.

hTERT gene immortalized human adipose-derived stem cells and its multiple differentiations: a preliminary investigation.

Science.gov (United States)

Wang, L; Song, K; Qu, X; Wang, H; Zhu, H; Xu, X; Zhang, M; Tang, Y; Yang, X

2013-03-01

Human adipose-derived adult stem cells (hADSCs) can express human telomerase reverse transcriptase phenotypes under an appropriate culture condition. Because adipose tissue is abundant and easily accessible, hADSCs offer a promising source of stem cells for tissue engineering application and other cell-based therapies. However, the shortage of cells number and the difficulty to proliferate, known as the "Hayflick limit" in vitro, limit their further clinical application. Here, hADSCs were transfected with human telomerase reverse transcriptase (hTERT) gene by the lentiviral vector to prolong the lifespan of stem cells and even immortalize them. Following to this, the cellular properties and functionalities of the transfected cell lines were assayed. The results demonstrated that hADSCs had been successfully transfected with hTERT gene (hTERT-ADSCs). Then, hTERT-ADSCs were initially selected by G418 and subsequently expanded over 20 passages in vitro. Moreover, the qualitative and quantitative differentiation criteria for 20 passages of hTERT-ADSCs also demonstrated that hTERT-ADSCs could differentiate into osteogenesis, chondrogenesis, and adipogenesis phenotypes in lineage-specific differentiation media. These findings confirmed that this transfection could prolong the lifespan of hADSCs.

Adipose derived stromal vascular fraction improves early tendon healing: an experimental study in rabbits

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Mehdi Behfar

2011-11-01

Full Text Available Tendon never restores the complete biological and mechanical properties after healing. Bone marrow and recently adipose tissue have been used as the sources of mesenchymal stem cells, which have been proven to enhance tendon healing. Stromal vascular fraction (SVF, derived from adipose tissue by an enzymatic digestion, represents an alternative source of multipotent cells, which undergo differentiation into multiple lineages to be used in regenerative medicine. In the present study, we investigated potentials of this source on tendon healing. Twenty rabbits were divided into control and treatment groups. Five rabbits were used as donors of adipose tissue. The injury model was unilateral complete transection through the middle one third of deep digital flexor tendon. Immediately after suture repair, either fresh stromal vascular fraction from enzymatic digestion of adipose tissue or placebo was intratendinously injected into the suture site in treatments and controls, respectively. Cast immobilization was continued for two weeks after surgery. Animals were sacrificed at the third week and tendons underwent histological, immunohistochemical, and mechanical evaluations. By histology, improved fibrillar organization and remodeling of neotendon were observed in treatment group. Immunohistochemistry revealed an insignificant increase in collagen type III and I expression in treatments over controls. Mechanical testing showed significant increase in maximum load and energy absorption in SVF treated tendons. The present study showed that intratendinous injection of uncultured adipose derived stromal vascular fraction improved structural and mechanical properties of repaired tendon and it could be an effective modality for treating tendon laceration.

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure

NARCIS (Netherlands)

Oedayrajsingh-Varma, M. J.; van Ham, S. M.; Knippenberg, M.; Helder, M. N.; Klein-Nulend, J.; Schouten, T. E.; Ritt, M. J. P. F.; van Milligen, F. J.

2006-01-01

Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

Science.gov (United States)

Kim, Dong Wook; Kim, Eun Ji; Kim, Eun Na; Sung, Myung Whun; Kwon, Tack-Kyun; Cho, Yong Woo; Kwon, Seong Keun

2016-01-01

Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

Effects of GSK3 inhibitors on in vitro expansion and differentiation of human adipose-derived stem cells into adipocytes

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Peraldi Pascal

2008-02-01

Full Text Available Abstract Background Multipotent stem cells exist within adipose tissue throughout life. An abnormal recruitment of these adipose precursor cells could participate to hyperplasia of adipose tissue observed in severe obesity or to hypoplasia of adipose tissue observed in lipodystrophy. Therefore, pharmacological molecules that control the pool of stem cells in adipose tissue are of great interest. Glycogen Synthase Kinase (GSK 3 has been previously described as involved in differentiation of preadipose cells and might be a potential therapeutic target to modulate proliferation and differentiation of adipocyte precursors. However, the impact of GSK3 inhibition on human adipose-derived stem cells remained to be investigated. The aim of this study was to investigate GSK3 as a possible target for pharmacological inhibition of stem cell adipogenesis. To reach this goal, we studied the effects of pharmacological inhibitors of GSK3, i.e. lithium chloride (LiCl and BIO on proliferation and adipocyte differentiation of multipotent stem cells derived from human adipose tissue. Results Our results showed that GSK3 inhibitors inhibited proliferation and clonogenicity of human stem cells, strongly suggesting that GSK3 inhibitors could be potent regulators of the pool of adipocyte precursors in adipose tissue. The impact of GSK3 inhibition on differentiation of hMADS cells was also investigated. Adipogenic and osteogenic differentiations were inhibited upon hMADS treatment with BIO. Whereas a chronic treatment was required to inhibit osteogenesis, a treatment that was strictly restricted to the early step of differentiation was sufficient to inhibit adipogenesis. Conclusion These results demonstrated the feasibility of a pharmacological approach to regulate adipose-derived stem cell function and that GSK3 could represent a potential target for controlling adipocyte precursor pool under conditions where fat tissue formation is impaired.

Adipose tissue engineering: state of the art, recent advances and innovative approaches.

Science.gov (United States)

Tanzi, Maria Cristina; Farè, Silvia

2009-09-01

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

International Nuclear Information System (INIS)

Li Huiwu; Dai Kerong; Tang Tingting; Zhang Xiaoling; Yan Mengning; Lou Jueren

2007-01-01

In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a β-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals

Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture

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Andrea V. Rozo

2017-07-01

Conclusion: These observations suggest that the acute activation of GLP1R in neonates durably alters hypothalamic architecture to limit adult weight gain and adiposity, identifying GLP1R as a therapeutic target for obesity prevention.

MicroRNA expression profiling in neurogenesis of adipose tissue

Indian Academy of Sciences (India)

Adipose tissue-derived stem cells (ADSCs) are one population of adult stem cells that can self renew and differentiate into multiple lineages. Because of advantages in method and quantity of acquisition, ADSCs are gaining attention as an alternative source of bone marrow mesenchymal stem cells. In this study, we ...

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

Directory of Open Access Journals (Sweden)

Dong Wook Kim

Full Text Available Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM and methylcellulose (MC for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

Tissue Source and Cell Expansion Condition Influence Phenotypic Changes of Adipose-Derived Stem Cells

Science.gov (United States)

Mangum, Lauren H.; Stone, Randolph; Wrice, Nicole L.; Larson, David A.; Florell, Kyle F.; Christy, Barbara A.; Herzig, Maryanne C.; Cap, Andrew P.

2017-01-01

Stem cells derived from the subcutaneous adipose tissue of debrided burned skin represent an appealing source of adipose-derived stem cells (ASCs) for regenerative medicine. Traditional tissue culture uses fetal bovine serum (FBS), which complicates utilization of ASCs in human medicine. Human platelet lysate (hPL) is one potential xeno-free, alternative supplement for use in ASC culture. In this study, adipogenic and osteogenic differentiation in media supplemented with 10% FBS or 10% hPL was compared in human ASCs derived from abdominoplasty (HAP) or from adipose associated with debrided burned skin (BH). Most (95–99%) cells cultured in FBS were stained positive for CD73, CD90, CD105, and CD142. FBS supplementation was associated with increased triglyceride content and expression of adipogenic genes. Culture in hPL significantly decreased surface staining of CD105 by 31% and 48% and CD142 by 27% and 35% in HAP and BH, respectively (p < 0.05). Culture of BH-ASCs in hPL also increased expression of markers of osteogenesis and increased ALP activity. These data indicate that application of ASCs for wound healing may be influenced by ASC source as well as culture conditions used to expand them. As such, these factors must be taken into consideration before ASCs are used for regenerative purposes. PMID:29138638

Tissue Source and Cell Expansion Condition Influence Phenotypic Changes of Adipose-Derived Stem Cells

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Lauren H. Mangum

2017-01-01

Full Text Available Stem cells derived from the subcutaneous adipose tissue of debrided burned skin represent an appealing source of adipose-derived stem cells (ASCs for regenerative medicine. Traditional tissue culture uses fetal bovine serum (FBS, which complicates utilization of ASCs in human medicine. Human platelet lysate (hPL is one potential xeno-free, alternative supplement for use in ASC culture. In this study, adipogenic and osteogenic differentiation in media supplemented with 10% FBS or 10% hPL was compared in human ASCs derived from abdominoplasty (HAP or from adipose associated with debrided burned skin (BH. Most (95–99% cells cultured in FBS were stained positive for CD73, CD90, CD105, and CD142. FBS supplementation was associated with increased triglyceride content and expression of adipogenic genes. Culture in hPL significantly decreased surface staining of CD105 by 31% and 48% and CD142 by 27% and 35% in HAP and BH, respectively (p<0.05. Culture of BH-ASCs in hPL also increased expression of markers of osteogenesis and increased ALP activity. These data indicate that application of ASCs for wound healing may be influenced by ASC source as well as culture conditions used to expand them. As such, these factors must be taken into consideration before ASCs are used for regenerative purposes.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling

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Ji-qing Cao

2016-01-01

Full Text Available Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells (6 × 10 6 were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR, eIF-4E binding protein 1 and S6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the regeneration and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Role of adipose-derived stem cells in wound healing.

Science.gov (United States)

Hassan, Waqar Ul; Greiser, Udo; Wang, Wenxin

2014-01-01

Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration. © 2014 by the Wound Healing Society.

Adipose-Derived Stem Cells

NARCIS (Netherlands)

Gathier, WA; Türktas, Z; Duckers, HJ

2015-01-01

Until recently bone marrow was perceived to be the only significant reservoir of stem cells in the body. However, it is now recognized that there are other and perhaps even more abundant sources, which include adipose tissue. Subcutaneous fat is readily available in most patients, and can easily be

Fitness and adiposity as predictors of functional limitation in adults.

Science.gov (United States)

Maslow, Andréa L; Price, Anna E; Sui, Xuemei; Lee, Duck-chul; Vuori, Ikka; Blair, Steven N

2011-01-01

This study examined the associations of body mass index (BMI), waist circumference (WC), and cardiorespiratory fitness (CRF) with incident functional limitation (IFL) in adults. Patients (n = 2400), 30+ years [mean age, 45.2 (SD, 8.3); 12% women], completed a baseline health examination during 1979 to 1995. CRF was quantified by age-and sex-specific thirds for maximal treadmill exercise test duration. Adiposity was assessed by BMI and WC (grouped for analysis according to clinical guidelines). Incident IFL was identified from mail-back surveys during 1995, 1999, and 2004. After adjusting for potential confounders and either BMI or WC, CRF was inversely related to IFL (P trend < .001). The association between BMI and IFL was significant after adjusting for all confounders (P trend = .002), but not after additional adjustment for CRF (P trend = .23). After controlling for all confounders and CRF, high WC was associated with greater odds of IFL in those aged 30 to 49; normal WC was associated with greater odds of IFL in those aged 50+. CRF was a significant predictor of IFL in middle aged and older adults, independent of overall or abdominal adiposity. Clinicians should consider the importance of preserving functional capacity by recommending regular physical activity for normal-weight and overweight individuals. ©2011 Human Kinetics, Inc.

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

Science.gov (United States)

2012-05-10

1% peni - cillin/streptomycin, and 50 ng/mL recombinant rat VEGF-C (Promocell, Heidelberg, Germany). The media were changed every other day for 8...various animal models that have demonstrated an enhanced osteogenic effect after treating bone allografts with adipose tissue or bone marrow-derived... enhanced 1560 CORNEJO ET AL. performance of bone allografts using osteogenic differentiated adipose derived mesenchymal stem cells. Biomaterials 32, 8880

The Pericytic Phenotype of Adipose Tissue-Derived Stromal Cells Is Promoted by NOTCH2

NARCIS (Netherlands)

Terlizzi, Vincenzo; Kolibabka, Matthias; Burgess, Janette Kay; Hammes, Hans Peter; Harmsen, Martin Conrad

Long-term diabetes leads to macrovascular and microvascular complication. In diabetic retinopathy (DR), persistent hyperglycemia causes permanent loss of retinal pericytes and aberrant proliferation of microvascular endothelial cells (ECs). Adipose tissue-derived stromal cells (ASCs) may serve to

CULTIVATION OF HUMAN LIVER CELLS AND ADIPOSE-DERIVED MESENCHYMAL STROMAL CELLS IN PERFUSION BIOREACTOR

Directory of Open Access Journals (Sweden)

Yu. В. Basok

2018-01-01

Full Text Available Aim: to show the progress of the experiment of cultivation of human liver cells and adipose-derived mesenchymal stromal cells in perfusion bioreactor.Materials and methods. The cultivation of a cell-engineered construct, consisting of a biopolymer microstructured collagen-containing hydrogel, human liver cells, adipose-derived mesenchymal stromal cells, and William’s E Medium, was performed in a perfusion bioreactor.Results. On the 7th day large cells with hepatocyte morphology – of a polygonal shape and a centrally located round nucleus, – were present in the culture chambers of the bioreactor. The metabolic activity of hepatocytes in cell-engineered constructs was confi rmed by the presence of urea in the culture medium on the seventh day of cultivation in the bioreactor and by the resorption of a biopolymer microstructured collagen-containing hydrogel.

Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

NARCIS (Netherlands)

Jurgens, W.J.F.M.; Oedayrajsingh-Varma, M.J.; Helder, M.N.; Zandieh Doulabi, B.; Schouten, T.E.; Kuik, D.J.; Ritt, M.J.P.F.; van Milligen-Kummer, F.J.

2008-01-01

The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to

Significance of adipose tissue-derived stem cells regulate CD4+ T cell immune in the treatment of multiple sclerosis

Directory of Open Access Journals (Sweden)

Yong-lin XIE

2014-10-01

Full Text Available Adipose tissue-derived stem cells (ADSCs are genetically engineered seed cells with immunomodulatory effects, widely used in the treatment of autoimmune diseases. This article focuses on the immunomodulatory effects of adipose tissue-derived stem cells on CD4+ T cell subsets, including T helper cell (Th 1, 2, 17 and regulatory T cell (Treg, and its clinical significance in the treatment of multiple sclerosis. doi: 10.3969/j.issn.1672-6731.2014.10.005

Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts.

Science.gov (United States)

Kakudo, Natsuko; Minakata, Tatsuya; Mitsui, Toshihito; Kushida, Satoshi; Notodihardjo, Frederik Zefanya; Kusumoto, Kenji

2008-11-01

This study evaluated changes in platelet-derived growth factor (PDGF)-AB and transforming growth factor (TGF)-beta1 release from platelets by platelet-rich plasma activation, and the proliferation potential of activated platelet-rich plasma and platelet-poor plasma on human adipose-derived stem cells and human dermal fibroblasts. Platelet-rich plasma was prepared using a double-spin method, with the number of platelets counted in each preparation stage. Platelet-rich and platelet-poor plasma were activated with autologous thrombin and calcium chloride, and levels of platelet-released PDGF-AB and TGF-beta1 were determined by enzyme-linked immunosorbent assay. Cells were cultured for 1, 4, or 7 days in serum-free Dulbecco's Modified Eagle Medium supplemented with 5% whole blood plasma, nonactivated platelet-rich plasma, nonactivated platelet-poor plasma, activated platelet-rich plasma, or activated platelet-poor plasma. In parallel, these cells were cultured for 1, 4, or 7 days in serum-free Dulbecco's Modified Eagle Medium supplemented with 1%, 5%, 10%, or 20% activated platelet-rich plasma. The cultured human adipose-derived stem cells and human dermal fibroblasts were assayed for proliferation. Platelet-rich plasma contained approximately 7.9 times as many platelets as whole blood, and its activation was associated with the release of large amounts of PDGF-AB and TGF-beta1. Adding activated platelet-rich or platelet-poor plasma significantly promoted the proliferation of human adipose-derived stem cells and human dermal fibroblasts. Adding 5% activated platelet-rich plasma to the medium maximally promoted cell proliferation, but activated platelet-rich plasma at 20% did not promote it. Platelet-rich plasma can enhance the proliferation of human adipose-derived stem cells and human dermal fibroblasts. These results support clinical platelet-rich plasma application for cell-based, soft-tissue engineering and wound healing.

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells.

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Shan, Xiaoyin; Roberts, Cleresa; Kim, Eun Ji; Brenner, Ariana; Grant, Gregory; Percec, Ivona

2017-05-01

Adult stem cells play a critical role in the maintenance of tissue homeostasis and prevention of aging. While the regenerative potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASCs), is increasingly recognized, the study of chronological aging in ASCs is technically difficult and remains poorly understood. Here, we use our model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks. We demonstrate first that the transcriptome of aging ASCs is distinctly more stable than that of age-matched fibroblasts, and further, that age-dependent modifications in cell cycle progression and translation initiation specifically characterize aging ASCs in conjunction with increased nascent protein synthesis and a distinctly shortened G1 phase. Our results reveal novel chronological aging mechanisms in ASCs that are inherently different from differentiated cells and that may reflect an organismal attempt to meet the increased demands of tissue and organ homeostasis during aging. Stem Cells 2017;35:1392-1401. © 2017 AlphaMed Press.

Does lower birth order amplify the association between high socio-economic status and central adiposity in young adult Filipino males?

OpenAIRE

Dahly, Darren L; Adair, Linda S

2010-01-01

Objective To test the hypothesis that lower birth order amplifies the positive association between socioeconomic status and central adiposity in young adult males from a lower-income, developing country context. Design The Cebu Longitudinal Health and Nutrition Survey is an ongoing community-based, observational study of a one year birth cohort (1983). Subjects 970 young adult males, mean age 21.5 y (2005). Measurements Central adiposity measured by waist circumference; birth order; perinatal...

Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells

NARCIS (Netherlands)

M. Roemeling-Van Rhijn (Marieke); F.K.F. Mensah (Fane ); S.S. Korevaar (Sander); M.J.C. Leijs (Maarten J.C.); G.J.V.M. van Osch (Gerjo); J.N.M. IJzermans (Jan); M.G.H. Betjes (Michiel); C.C. Baan (Carla); W. Weimar (Willem); M.J. Hoogduijn (Martin)

2013-01-01

textabstractAdipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower

The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.

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Wrage, Philip C; Tran, Thi; To, Khai; Keefer, Edward W; Ruhn, Kelly A; Hong, John; Hattangadi, Supriya; Treviño, Isaac; Tansey, Malú G

2008-01-16

We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key

Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

Science.gov (United States)

Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

2016-09-01

Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity.

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Christou, Demetra D; Pierce, Gary L; Walker, Ashley E; Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Meade, Thomas H; English, Mark; Seals, Douglas R

2012-09-15

Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18-79 years; body mass index (BMI), 16.4-42.2 kg/m(2)], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI and percent body fat (percent BF via dual-energy X-ray absorptiometry)], and indexes of abdominal adiposity [waist circumference (WC) and waist-to-hip ratio (WHR)]. In a subgroup (n = 74), we also measured total abdominal fat (TAF), abdominal visceral fat (AVF), and subcutaneous fat (ASF) using computed tomography. Based on multiple linear regression, NID was negatively related to BMI [part correlation coefficient (r(part)) = -0.19, P = 0.004] and abdominal adiposity (WC, r(part) = -0.22; WHR, r(part) = -0.19; TAF, r(part) = -0.36; AVF, r(part) = -0.36; and ASF, r(part) = -0.30; all P ≤ 0.009) independent of sex, but only tended to be related to total percent BF (r(part) = -0.12, P = 0.07). In a subgroup of subjects with the highest compared with the lowest amount of AVF, NID was 35% lower (P = 0.003). Accounting for systolic blood pressure, HDL cholesterol, glucose, insulin resistance, adiponectin, and brachial artery diameter reduced or abolished some of the relations between NID and adiposity. In conclusion, NID is or tends to be negatively associated with measures of total adiposity (BMI and percent BF, respectively) but is consistently and more strongly negatively associated with abdominal adiposity. Adiposity may influence NID in part via other cardiovascular risk factors.

In vitro effects of direct current electric fields on adipose-derived stromal cells.

Science.gov (United States)

Hammerick, Kyle E; Longaker, Michael T; Prinz, Fritz B

2010-06-18

Endogenous electric fields play an important role in embryogenesis, regeneration, and wound repair and previous studies have shown that many populations of cells, leukocytes, fibroblasts, epithelial cells, and endothelial cells, exhibit directed migration in response to electric fields. As regenerative therapies continue to explore ways to control mesenchymal progenitor cells to recreate desirable tissues, it is increasingly necessary to characterize the vast nature of biological responses imposed by physical phenomena. Murine adipose-derived stromal cells (mASCs) migrated toward the cathode in direct current (DC) fields of physiologic strength and show a dose dependence of migration rate to stronger fields. Electric fields also caused mASCs to orient perpendicularly to the field vector and elicited a transient increase in cytosolic calcium. Additionally, their galvanotactic response appears to share classic chemotactic signaling pathways that are involved in the migration of other cell types. Galvanotaxis is one predominant result of electric fields on mASCs and it may be exploited to engineer adult stem cell concentrations and locations within implanted grafts or toward sites of wound repair. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

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Diana Vargas

2017-01-01

Full Text Available Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases.

Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

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MW Laschke

2014-10-01

Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

Human Adipose-Derived Stem Cells on Rapid Prototyped Three-Dimensional Hydroxyapatite/Beta-Tricalcium Phosphate Scaffold.

Science.gov (United States)

Canciani, Elena; Dellavia, Claudia; Ferreira, Lorena Maria; Giannasi, Chiara; Carmagnola, Daniela; Carrassi, Antonio; Brini, Anna Teresa

2016-05-01

In the study, we assess a rapid prototyped scaffold composed of 30/70 hydroxyapatite (HA) and beta-tricalcium-phosphate (β-TCP) loaded with human adipose-derived stem cells (hASCs) to determine cell proliferation, differentiation toward osteogenic lineage, adhesion and penetration on/into the scaffold.In this in vitro study, hASCs isolated from fat tissue discarded after plastic surgery were expanded, characterized, and then loaded onto the scaffold. Cells were tested for: viability assay (Alamar Blue at days 3, 7 and Live/Dead at day 32), differentiation index (alkaline phosphatase activity at day 14), scaffold adhesion (standard error of the mean analysis at days 5 and 18), and penetration (ground sections at day 32).All the hASC populations displayed stemness markers and the ability to differentiate toward adipogenic and osteogenic lineages.Cellular vitality increased between 3 and 7 days, and no inhibitory effect by HA/β-TCP was observed. Under osteogenic stimuli, scaffold increased alkaline phosphatase activity of +243% compared with undifferentiated samples. Human adipose-derived stem cells adhered on HA/β-TCP surface through citoplasmatic extensions that occupied the macropores and built networks among them. Human adipose derived stem cells were observed in the core of HA/β-TCP. The current combination of hASCs and HA/β-TCP scaffold provided encouraging results. If authors' data will be confirmed in preclinical models, the present engineering approach could represent an interesting tool in treating large bone defects.

The differentiation potential of adipose tissue-derived mesenchymal stem cells into cell lineage related to male germ cells

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P. Bräunig

Full Text Available ABSTRACT The adipose tissue is a reliable source of Mesenchymal stem cells (MSCs showing a higher plasticity and transdifferentiation potential into multilineage cells. In the present study, adipose tissue-derived mesenchymal stem cells (AT-MSCs were isolated from mice omentum and epididymis fat depots. The AT-MSCs were initially compared based on stem cell surface markers and on the mesodermal trilineage differentiation potential. Additionally, AT-MSCs, from both sources, were cultured with differentiation media containing retinoic acid (RA and/or testicular cell-conditioned medium (TCC. The AT-MSCs expressed mesenchymal surface markers and differentiated into adipogenic, chondrogenic and osteogenic lineages. Only omentum-derived AT-MSCs expressed one important gene marker related to male germ cell lineages, after the differentiation treatment with RA. These findings reaffirm the importance of adipose tissue as a source of multipotent stromal-stem cells, as well as, MSCs source regarding differentiation purpose.

Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

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Aimee L. Dordevic

2015-07-01

Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

Does lower birth order amplify the association between high socioeconomic status and central adiposity in young adult Filipino males?

Science.gov (United States)

Dahly, D L; Adair, L S

2010-04-01

To test the hypothesis that lower birth order amplifies the positive association between socioeconomic status and central adiposity in young adult males from a lower income, developing country context. The Cebu Longitudinal Health and Nutrition Survey is an ongoing community-based, observational study of a 1-year birth cohort (1983). 970 young adult males, mean age 21.5 years (2005). Central adiposity measured by waist circumference; birth order; perinatal maternal characteristics including height, arm fat area, age and smoking behavior; socioeconomic status at birth and in young adulthood. Lower birth order was associated with higher waist circumference and increased odds of high waist circumference, even after adjustment for socioeconomic status in young adulthood and maternal characteristics that could impact later offspring adiposity. Furthermore, the positive association between socioeconomic status and central adiposity was amplified in individuals characterized by lower birth order. This research has failed to reject the mismatch hypothesis, which posits that maternal constraint of fetal growth acts to program developing physiology in a manner that increases susceptibility to the obesogenic effects of modern environments.

Interaction between adipose tissue-derived mesenchymal stem cells and regulatory T-cells

OpenAIRE

Engela, Anja; Baan, Carla; Peeters, Anna; Weimar, Willem; Hoogduijn, Martin

2013-01-01

textabstractMesenchymal stem cells (MSCs) exhibit immunosuppressive capabilities, which have evoked interest in their application as cell therapy in transplant patients. So far it has been unclear whether allogeneic MSCs and host regulatory T-cells (Tregs) functionally influence each other. We investigated the interaction between both cell types using perirenal adipose tissue-derived MSCs (ASCs) from kidney donors and Tregs from blood bank donors or kidney recipients 6 months after transplant...

Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

Science.gov (United States)

Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

2016-03-31

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults

NARCIS (Netherlands)

Graff, Mariaelisa; Scott, Robert A; Justice, Anne E; Young, Kristin L; Feitosa, Mary F; Barata, Llilda; Winkler, Thomas W; Chu, Audrey Y; Mahajan, Anubha; Hadley, David; Xue, Luting; Workalemahu, Tsegaselassie; Heard-Costa, Nancy L; den Hoed, Marcel; Ahluwalia, Tarunveer S; Qi, Qibin; Ngwa, Julius S; Renström, Frida; Quaye, Lydia; Eicher, John D; Hayes, James E; Cornelis, Marilyn; Kutalik, Zoltan; Lim, Elise; Luan, Jian'an; Huffman, Jennifer E; Zhang, Weihua; Zhao, Wei; Griffin, Paula J; Haller, Toomas; Ahmad, Shafqat; Marques-Vidal, Pedro M; Bien, Stephanie; Yengo, Loic; Teumer, Alexander; Smith, Albert Vernon; Kumari, Meena; Harder, Marie Neergaard; Justesen, Johanne Marie; Kleber, Marcus E; Hollensted, Mette; Lohman, Kurt; Rivera, Natalia V; Whitfield, John B; Zhao, Jing Hua; Stringham, Heather M; Lyytikäinen, Leo-Pekka; Huppertz, Charlotte; Willemsen, Gonneke; Peyrot, Wouter J; Wu, Ying; Kristiansson, Kati; Demirkan, Ayse; Fornage, Myriam; Hassinen, Maija; Bielak, Lawrence F; Cadby, Gemma; Tanaka, Toshiko; Mägi, Reedik; van der Most, Peter J; Jackson, Anne U; Bragg-Gresham, Jennifer L; Vitart, Veronique; Marten, Jonathan; Navarro, Pau; Bellis, Claire; Pasko, Dorota; Johansson, Åsa; Snitker, Søren; Cheng, Ching-Yu; Eriksson, Joel; Lim, Unhee; Aadahl, Mette; Adair, Linda S; Amin, Najaf; Balkau, Beverley; Auvinen, Juha; Beilby, John; Bergman, Richard N; Bergmann, Sven; Bertoni, Alain G; Blangero, John; Bonnefond, Amélie; Bonnycastle, Lori L; Borja, Judith B; Brage, Søren; Busonero, Fabio; Buyske, Steve; Campbell, Harry; Chines, Peter S; Collins, Francis S; Corre, Tanguy; Smith, George Davey; Delgado, Graciela E; Dueker, Nicole; Dörr, Marcus; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Faul, Jessica D; Fu, Mao; Færch, Kristine; Gieger, Christian; Gläser, Sven; Gong, Jian; Gordon-Larsen, Penny; Grallert, Harald; Grammer, Tanja B; Grarup, Niels; van Grootheest, Gerard; Harald, Kennet; Hastie, Nicholas D; Havulinna, Aki S; Hernandez, Dena G; Hindorff, Lucia; Hocking, Lynne J; Holmens, Oddgeir L; Holzapfel, Christina; Hottenga, Jouke Jan; Huang, Jie; Huang, Tao; Hui, Jennie; Huth, Cornelia; Hutri-Kähönen, Nina; James, Alan L; Jansson, John-Olov; Jhun, Min A; Juonala, Markus; Kinnunen, Leena; Koistinen, Heikki A; Kolcic, Ivana; Komulainen, Pirjo; Kuusisto, Johanna; Kvaløy, Kirsti; Kähönen, Mika; Lakka, Timo A; Launer, Lenore J; Lehne, Benjamin; Lindgren, Cecilia M; Lorentzon, Mattias; Luben, Robert; Marre, Michel; Milaneschi, Yuri; Monda, Keri L; Montgomery, Grant W; De Moor, Marleen H M; Mulas, Antonella; Müller-Nurasyid, Martina; Musk, A.W.; Männikkö, Reija; Männistö, Satu; Narisu, Narisu; Nauck, Matthias; Nettleton, Jennifer A; Nolte, Ilja M; Oldehinkel, Albertine J; Olden, Matthias; Ong, Ken K; Padmanabhan, Sandosh; Paternoster, Lavinia; Perez, Jeremiah; Perola, Markus; Peters, Annette; Peters, Ulrike; Peyser, Patricia A; Prokopenko, Inga; Puolijoki, Hannu; Raitakari, Olli T; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rawal, Rajesh; Ridker, Paul M; Rose, Lynda M; Rudan, Igor; Sarti, Cinzia; Sarzynski, Mark A; Savonen, Kai; Scott, William R; Sanna, Serena; Shuldiner, Alan R; Sidney, Steve; Silbernagel, Günther; Smith, Blair H; Smith, Jennifer A; Snieder, Harold; Stančáková, Alena; Sternfeld, Barbara; Swift, Amy J; Tammelin, Tuija; Tan, Sian-Tsung; Thorand, Barbara; Thuillier, Dorothée; Vandenput, Liesbeth; Vestergaard, Henrik; van Vliet-Ostaptchouk, Jana V; Vohl, Marie-Claude; Völker, Uwe; Waeber, Gérard; Walker, Mark; Wild, Sarah; Wong, Andrew; Wright, Alan F; Zillikens, M Carola; Zubair, Niha; Haiman, Christopher A; Lemarchand, Loic; Gyllensten, Ulf; Ohlsson, Claes; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Pérusse, Louis; Wilson, James F; Hayward, Caroline; Polasek, Ozren; Cucca, Francesco; Hveem, Kristian; Hartman, Catharina A; Tönjes, Anke; Bandinelli, Stefania; Palmer, Lyle J; Kardia, Sharon L R; Rauramaa, Rainer; Sørensen, Thorkild I A; Tuomilehto, Jaakko; Salomaa, Veikko; Penninx, Brenda W J H; de Geus, Eco J C; Boomsma, Dorret I; Lehtimäki, Terho; Mangino, Massimo; Laakso, Markku; Bouchard, Claude; Martin, Nicholas G; Kuh, Diana; Liu, YongMei; Linneberg, Allan; März, Winfried; Strauch, Konstantin; Kivimäki, Mika; Harris, Tamara B; Gudnason, Vilmundur; Völzke, Henry; Qi, Lu; Järvelin, Marjo-Riitta; Chambers, John C; Kooner, Jaspal S; Froguel, Philippe; Kooperberg, Charles; Vollenweider, Peter; Hallmans, Göran; Hansen, Torben; Pedersen, Oluf; Metspalu, Andres; Wareham, Nicholas J; Langenberg, Claudia; Weir, David R; Porteous, David J; Boerwinkle, Eric; Chasman, Daniel I; Abecasis, Gonçalo R; Barroso, Inês; McCarthy, Mark I; Frayling, Timothy M; O'Connell, Jeffrey R; van Duijn, Cornelia M; Boehnke, Michael; Heid, Iris M; Mohlke, Karen L; Strachan, David P; Fox, Caroline S; Liu, Ching-Ti; Hirschhorn, Joel N; Klein, Robert J; Johnson, Andrew D; Borecki, Ingrid B; Franks, Paul W; North, Kari E; Cupples, L Adrienne; Loos, Ruth J F; Kilpeläinen, Tuomas O

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults

Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cells function for soft tissue regeneration

Science.gov (United States)

Li, Hong-Mian; Peng, Qi-Liu; Huang, Min-Hong; Li, De-Quan; Liang, Yi-Dan; Chi, Gang-Yi; Li, De-Hui; Yu, Bing-Chao; Huang, Ji-Rong

2016-01-01

Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering. PMID:27191987

Obesity and central adiposity in Mexican adults: results from the Mexican National Health and Nutrition Survey 2006.

Science.gov (United States)

Barquera, Simón; Campos-Nonato, Ismael; Hernández-Barrera, Lucía; Flores, Mario; Durazo-Arvizu, Ramón; Kanter, Rebecca; Rivera, Juan A

2009-01-01

To estimate the prevalence of overweight, obesity and central adiposity in Mexico, and to explore trends compared to the previous Mexican National Health Survey (ENSA 2000) and to Mexican-Americans. The Mexican National Health and Nutrition Survey 2006 (ENSANUT 2006) was used to describe overweight, obesity and central adiposity. Trends over time were assessed using the ENSA 2000 and by comparing the ENSANUT 2006 results to those of Mexican-Americans using the United States National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2005-2006. A total of 33023 adults > 20 years old were included; 39.7% were found to be overweight and 29.9% were found to be obese; 75.9% of all adults had abdominal obesity. In Mexico between 2000 and 2006, the combined prevalence of overweight and obesity in adults increased approximately 12%. Mexican-Americans showed a higher prevalence of morbid obesity compared to native Mexicans. Mexico has experienced a rapid increase in the number of adults who have experienced excess weight gain between the years 2000 and 2006.

Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

International Nuclear Information System (INIS)

Timper, Katharina; Seboek, Dalma; Eberhardt, Michael; Linscheid, Philippe; Christ-Crain, Mirjam; Keller, Ulrich; Mueller, Beat; Zulewski, Henryk

2006-01-01

Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin

Carotenoids in Adipose Tissue Biology and Obesity.

Science.gov (United States)

Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

2016-01-01

Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

Investigating the Bidirectional Associations of Adiposity with Sleep Duration in Older Adults: The English Longitudinal Study of Ageing (ELSA).

Science.gov (United States)

Garfield, Victoria; Llewellyn, Clare H; Steptoe, Andrew; Kumari, Meena

2017-01-09

Cross-sectional analyses of adiposity and sleep duration in younger adults suggest that increased adiposity is associated with shorter sleep. Prospective studies have yielded mixed findings, and the direction of this association in older adults is unclear. We examined the cross-sectional and potential bi-directional, prospective associations between adiposity and sleep duration (covariates included demographics, health behaviours, and health problems) in 5,015 respondents from the English Longitudinal Study of Ageing (ELSA), at baseline and follow-up. Following adjustment for covariates, we observed no significant cross-sectional relationship between body mass index (BMI) and sleep duration [(unstandardized) B = -0.28 minutes, (95% Confidence Intervals (CI) = -0.012; 0.002), p = 0.190], or waist circumference (WC) and sleep duration [(unstandardized) B = -0.10 minutes, (95% CI = -0.004; 0.001), p = 0.270]. Prospectively, both baseline BMI [B = -0.42 minutes, (95% CI = -0.013; -0.002), p = 0.013] and WC [B = -0.18 minutes, (95% CI = -0.005; -0.000), p = 0.016] were associated with decreased sleep duration at follow-up, independently of covariates. There was, however, no association between baseline sleep duration and change in BMI or WC (p > 0.05). In older adults, our findings suggested that greater adiposity is associated with decreases in sleep duration over time; however the effect was very small.

Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

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Kabiri, Azadeh, E-mail: z_kabiri@resident.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esfandiari, Ebrahim, E-mail: esfandiari@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Hashemibeni, Batool, E-mail: hashemibeni@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Kazemi, Mohammad, E-mail: m_kazemi@med.mui.ac.i [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Mardani, Mohammad, E-mail: mardani@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esmaeili, Abolghasem, E-mail: abesmaeili@yahoo.com [Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan (Iran, Islamic Republic of)

2012-07-27

Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

International Nuclear Information System (INIS)

Kabiri, Azadeh; Esfandiari, Ebrahim; Hashemibeni, Batool; Kazemi, Mohammad; Mardani, Mohammad; Esmaeili, Abolghasem

2012-01-01

Highlights: ► We investigated effects of FGF-2 on hADSCs. ► We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. ► FGF-2 induces chondrogenesis in hADSCs, which •Increasing information will decrease quality if hospital costs are very different. ► The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

Adipose-derived mesenchymal stem cells accelerate nerve regeneration and functional recovery in a rat model of recurrent laryngeal nerve injury

Directory of Open Access Journals (Sweden)

Yun Li

2017-01-01

Full Text Available Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated whether adipose-derived stem cell transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 × 105 or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8 × 105 or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellular matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.

Childhood social class and adult adiposity and blood-pressure trajectories 36-53 years: gender-specific results from a British birth cohort.

Science.gov (United States)

Strand, Bjørn Heine; Murray, Emily T; Guralnik, Jack; Hardy, Rebecca; Kuh, Diana

2012-06-01

In this study, the authors investigate gender-specific effects of childhood socio-economic position (SEP) on adiposity and blood pressure at three time points in adulthood. Mixed models were used to assess the association of childhood SEP with body mass index (BMI), waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) at ages 36, 43 and 53 years in a British birth cohort. The adverse effect of lower childhood SEP on adiposity increased between ages 36 and 53 years in women (BMI: trend test: p=0.03) and remained stable in men, but the opposite was seen for SBP, where inequalities increased in men (p=0.01). Childhood SEP inequalities in DBP were stable with age in both men and women. Educational attainment mediated some but not all of the effects of childhood SEP on adiposity and SBP, and their rate of change; adult social class was a less important mediator. Childhood SEP is important for adult adiposity and blood pressure across midlife, especially for BMI in women and for blood pressure in men. Thus, pathways to adult health differ for men and women, and public health policies aimed at reducing social inequalities need to start early in life and take account of gender.

Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells.

Science.gov (United States)

Lee, Jae Geun; Bak, Seon Young; Nahm, Ji Hae; Lee, Sang Woo; Min, Seon Ok; Kim, Kyung Sik

2015-05-01

Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds. This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days. Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days. Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial.

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

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Takahara, Kiyoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Asahi, Michio [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Azuma, Haruhito [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan)

2014-04-18

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

International Nuclear Information System (INIS)

Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

2014-01-01

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa

Methodologies to assess paediatric adiposity.

LENUS (Irish Health Repository)

Horan, M

2014-05-04

Childhood obesity is associated with increased risk of adult obesity, cardiovascular disease, diabetes and cancer. Appropriate techniques for assessment of childhood adiposity are required to identify children at risk. The aim of this review was to examine core clinical measurements and more technical tools to assess paediatric adiposity.

Enhancement of human adipose-derived stem cell expansion and stability for clinical use

OpenAIRE

Krähenbühl, S. M.

2016-01-01

Co-culture techniques associating both dermal fibroblasts and epidermal keratinocytes have shown to have better clinical outcome than keratinocyte culture alone for the treatment of severe burns. Since fat grafting has been shown to improve scar remodelling, new techniques such as cell-therapy-assisted surgical reconstruction with isolated and expanded autologous adipose-derived stem cells (ASCs) would be of benefit to increase graft acceptation. Therefore, integrating ASCs into s...

Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

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Magali Kouidhi

2015-01-01

Full Text Available Animal study findings have revealed that individual fat depots are not functionally equivalent and have different embryonic origins depending on the anatomic location. Mouse bone regeneration studies have also shown that it is essential to match the Hox code of transplanted cells and host tissues to achieve correct repair. However, subcutaneous fat depots from any donor site are often used in autologous fat grafting. Our study was thus carried out to determine the embryonic origins of human facial (chin and limb (knee fat depots and whether they had similar features and molecular matching patterns. Paired chin and knee fat depots were harvested from 11 subjects and gene expression profiles were determined by DNA microarray analyses. Adipose-derived stromal cells (ASCs from both sites were isolated and analyzed for their capacity to proliferate, form clones, and differentiate. Chin and knee fat depots expressed a different HOX code and could have different embryonic origins. ASCs displayed a different phenotype, with chin-ASCs having the potential to differentiate into brown-like adipocytes, whereas knee-ASCs differentiated into white adipocytes. These results highlighted different features for these two fat sites and indicated that donor site selection might be an important factor to be considered when applying adipose tissue in cell-based therapies.

Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation.

Science.gov (United States)

Titos, Esther; Clària, Joan

2013-12-01

Chronic low-grade inflammation in adipose tissue has been recognized as a key step in the development of obesity-associated complications. In obesity, the accumulation of infiltrating macrophages in adipose tissue and their phenotypic switch to M1-type dysregulate inflammatory adipokine production leading to obesity-linked insulin resistance. Resolvins are potent anti-inflammatory and pro-resolving mediators endogenously generated from omega-3 fatty acids that act as "stop-signals" of the inflammatory response promoting the resolution of inflammation. Recently, a deficit in the production of these endogenous anti-inflammatory signals has been demonstrated in obese adipose tissue. The restoration of their levels by either exogenous administration of these mediators or feeding omega-3-enriched diets, improves the inflammatory status of adipose tissue and ameliorates metabolic dysfunction. Here, we review the current knowledge on the role of these endogenous autacoids in the resolution of adipose tissue inflammation with special emphasis on their functional actions on macrophages. Copyright © 2013 Elsevier Inc. All rights reserved.

Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

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Jeonghwan Lee

Full Text Available Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61, P for trend 0.016, for the comparisons of lowest vs. highest quartile and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75, P for trend < 0.001 in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2, male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80, P for trend = 0.009. Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49, P for trend = 0.002. After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25, P for trend = 0.013. Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

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Mariaelisa Graff

2017-04-01

Full Text Available Physical activity (PA may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423 or other ancestry (n = 20,029. We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Are adipose-derived stem cells cultivated in human platelet lysate suitable for heart valve tissue engineering?

NARCIS (Netherlands)

Frese, L.; Sasse, T.; Sanders, B.; Baaijens, F.P.T.; Beer, G.M.; Hoerstrup, S.P.

2017-01-01

Tissue-engineered heart valves represent a promising strategy for the growing need for valve replacements in cardiovascular medicine. Recent studies have shown that adipose-derived stem cells (ADSC) are a viable cell source, as they are readily available in both the young and the elderly, show

Adipose-Derived-Stem-Cell-Seeded Fibrin Matrices for Periodontal Ligament Engineering: The Need for Dynamic Strain

NARCIS (Netherlands)

de Jong, Thijs; Oostendorp, Corien; Bakker, Astrid D.; van Kuppevelt, Toin H.; Smit, Theo H.

2017-01-01

Introduction: The periodontal ligament (PDL) connects the tooth to the alveolar bone. For PDL regeneration after tissue damage, we propose human adipose-derived stem cells (hASCs) embedded in fibrin. We showed previously that hASCs in fibrin extensively produce collagen, but in a non-functional,

Neural differentiation of adipose-derived stem cells isolated from GFP transgenic mice

International Nuclear Information System (INIS)

Fujimura, Juri; Ogawa, Rei; Mizuno, Hiroshi; Fukunaga, Yoshitaka; Suzuki, Hidenori

2005-01-01

Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have recently reported that adipose-derived stromal cells (ASCs) could differentiate into mesenchymal lineages in vitro. In this study, we performed neural induction using ASCs from GFP transgenic mice and were able to induce these ASCs into neuronal and glial cell lineages. Most of the neurally induced cells showed bipolar or multipolar appearance morphologically and expressed neuronal markers. Electron microscopy revealed their neuronal morphology. Some cells also showed glial phenotypes, as shown immunocytochemically. The present study clearly shows that ASCs derived from GFP transgenic mice differentiate into neural lineages in vitro, suggesting that these cells might provide an ideal source for further neural stem cell research with possible therapeutic application for neurological disorders

Kojyl cinnamate ester derivatives promote adiponectin production during adipogenesis in human adipose tissue-derived mesenchymal stem cells.

Science.gov (United States)

Rho, Ho Sik; Hong, Soo Hyun; Park, Jongho; Jung, Hyo-Il; Park, Young-Ho; Lee, John Hwan; Shin, Song Seok; Noh, Minsoo

2014-05-01

The subcutaneous fat tissue mass gradually decreases with age, and its regulation is a strategy to develop anti-aging compounds to ameliorate the photo-aging of human skin. The adipogenesis of human adipose tissue-mesenchymal stem cells (hAT-MSCs) can be used as a model to discover novel anti-aging compounds. Cinnamomum cassia methanol extracts were identified as adipogenesis-promoting agents by natural product library screening. Cinnamates, the major chemical components of Cinnamomum cassia extracts, promoted adipogenesis in hAT-MSCs. We synthesized kojyl cinnamate ester derivatives to improve the pharmacological activity of cinnamates. Structure-activity studies of kojyl cinnamate derivatives showed that both the α,β-unsaturated carbonyl ester group and the kojic acid moiety play core roles in promoting adiponectin production during adipogenesis in hAT-MSCs. We conclude that kojyl cinnamate ester derivatives provide novel pharmacophores that can regulate adipogenesis in hAT-MSCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Associations between accelerometer-derived physical activity and regional adiposity in young men and women.

Science.gov (United States)

Smith, H A; Storti, K L; Arena, V C; Kriska, A M; Gabriel, K K Pettee; Sutton-Tyrrell, K; Hames, K C; Conroy, M B

2013-06-01

Empirical evidence supports an inverse relationship between physical activity (PA) and adiposity, but studies using detailed measures of both are scarce. The relationship between regional adiposity and accelerometer-derived PA in men and women are described. Cross-sectional analysis included 253 participants from a weight loss study limited to ages 20-45 years and BMI 25-39.9 kg m(-2) . PA data were collected with accelerometers and expressed as total accelerometer counts and average amount of time per day accumulated in different intensity levels [sedentary, light-, and moderate-to-vigorous intensity PA (MVPA)]. Accumulation of time spent above 100 counts was expressed as total active time. Computed tomography (CT) was used to measure abdominal and adipose tissue (AT). Multivariate linear regression analyses were used to assess the relationship between regional adiposity (dependent variable) and the various PA levels (independent variable), and were executed separately for men and women, adjusting for wear time, age, race, education, and BMI. Among males, light activity was inversely associated with total AT (β = -0.19; P = 0.02) as well as visceral AT (VAT) (β = -0.30; P = 0.03). Among females sedentary time was positively associated with VAT (β = 0.11; P = 0.04) and total active time was inversely associated with VAT (β = -0.12; P = 0.04). Findings from this study suggest that PA intensity level may influence regional adiposity differently in men and women. Additional research is needed in larger samples to clarify the difference in these associations by sex, create recommendations for the frequency, duration and intensity of PA needed to target fat deposits, and determine if these recommendations should differ by sex. Copyright © 2013 The Obesity Society.

Waist Circumference, Body Mass Index, and Other Measures of Adiposity in Predicting Cardiovascular Disease Risk Factors among Peruvian Adults.

Science.gov (United States)

Knowles, K M; Paiva, L L; Sanchez, S E; Revilla, L; Lopez, T; Yasuda, M B; Yanez, N D; Gelaye, B; Williams, M A

2011-01-24

Objectives. To examine the extent to which measures of adiposity can be used to predict selected components of metabolic syndrome (MetS) and elevated C-reactive protein (CRP). Methods. A total of 1,518 Peruvian adults were included in this study. Waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHtR), and visceral adiposity index (VAI) were examined. The prevalence of each MetS component was determined according to tertiles of each anthropometric measure. ROC curves were used to evaluate the extent to which measures of adiposity can predict cardiovascular risk. Results. All measures of adiposity had the strongest correlation with triglyceride concentrations (TG). For both genders, as adiposity increased, the prevalence of Mets components increased. Compared to individuals with low-BMI and low-WC, men and women with high-BMI and high- WC had higher odds of elevated fasting glucose, blood pressure, TG, and reduced HDL, while only men in this category had higher odds of elevated CRP. Overall, the ROCs showed VAI, WC, and WHtR to be the best predictors for individual MetS components. Conclusions. The results of our study showed that measures of adiposity are correlated with cardiovascular risk although no single adiposity measure was identified as the best predictor for MetS.

Ultrasound-assisted liposuction provides a source for functional adipose-derived stromal cells.

Science.gov (United States)

Duscher, Dominik; Maan, Zeshaan N; Luan, Anna; Aitzetmüller, Matthias M; Brett, Elizabeth A; Atashroo, David; Whittam, Alexander J; Hu, Michael S; Walmsley, Graham G; Houschyar, Khosrow S; Schilling, Arndt F; Machens, Hans-Guenther; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

2017-12-01

Regenerative medicine employs human mesenchymal stromal cells (MSCs) for their multi-lineage plasticity and their pro-regenerative cytokine secretome. Adipose-derived mesenchymal stromal cells (ASCs) are concentrated in fat tissue, and the ease of harvest via liposuction makes them a particularly interesting cell source. However, there are various liposuction methods, and few have been assessed regarding their impact on ASC functionality. Here we study the impact of the two most popular ultrasound-assisted liposuction (UAL) devices currently in clinical use, VASER (Solta Medical) and Lysonix 3000 (Mentor) on ASCs. After lipoaspirate harvest and processing, we sorted for ASCs using fluorescent-assisted cell sorting based on an established surface marker profile (CD34 + CD31 - CD45 - ). ASC yield, viability, osteogenic and adipogenic differentiation capacity and in vivo regenerative performance were assessed. Both UAL samples demonstrated equivalent ASC yield and viability. VASER UAL ASCs showed higher osteogenic and adipogenic marker expression, but a comparable differentiation capacity was observed. Soft tissue healing and neovascularization were significantly enhanced via both UAL-derived ASCs in vivo, and there was no significant difference between the cell therapy groups. Taken together, our data suggest that UAL allows safe and efficient harvesting of the mesenchymal stromal cellular fraction of adipose tissue and that cells harvested via this approach are suitable for cell therapy and tissue engineering applications. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells

International Nuclear Information System (INIS)

Kakudo, Natsuko; Shimotsuma, Ayuko; Kusumoto, Kenji

2007-01-01

Adipose-derived stem cells (ASCs) have demonstrated a capacity for differentiating into a variety of lineages, including bone, cartilage, or fat, depending on the inducing stimuli and specific growth and factors. It is acknowledged that fibroblast growth factor-2 (FGF-2) promotes chondrogenic and inhibits osteogenic differentiation of ASCs, but thorough investigations of its effects on adipogenic differentiation are lacking. In this study, we demonstrate at the cellular and molecular levels the effect of FGF-2 on adipogenic differentiation of ASCs, as induced by an adipogenic hormonal cocktail consisting of 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, insulin, and indomethacin. FGF-2 significantly enhances the adipogenic differentiation of human ASCs. Furthermore, in cultures receiving FGF-2 before adipogenic induction, mRNA expression of peroxisome proliferator-activated receptor γ2 (PPARγ2), a key transcription factor in adipogenesis, was upregulated. The results of FGF-2 supplementation suggest the potential applications of FGF-2 and ASCs in adipose tissue regeneration

Adiposity Impacts Intrarenal Hemodynamic Function in Adults With Long-standing Type 1 Diabetes With and Without Diabetic Nephropathy: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Science.gov (United States)

Bjornstad, Petter; Lovshin, Julie A; Lytvyn, Yuliya; Boulet, Genevieve; Lovblom, Leif E; Alhuzaim, Omar N; Farooqi, Mohammed A; Lai, Vesta; Tse, Josephine; Cham, Leslie; Orszag, Andrej; Scarr, Daniel; Weisman, Alanna; Keenan, Hillary A; Brent, Michael H; Paul, Narinder; Bril, Vera; Perkins, Bruce A; Cherney, David Z I

2018-04-01

Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). Patients with type 1 diabetes ( n = 66, duration ≥50 years) and age-/sex-matched control subjects ( n = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m 2 and inulin [GFR INULIN ], effective renal plasma flow for p -aminohippuric acid [ERPF PAH ]) was measured. Afferent arteriolar resistance, efferent arteriolar resistance, renal blood flow, renal vascular resistance [RVR], filtration fraction, and glomerular pressure were derived from the Gomez equations. Fat and lean mass were quantified by DXA. Whereas measures of adiposity did not associate with GFR INULIN or ERPF PAH in healthy control subjects, trunk fat mass inversely correlated with GFR INULIN ( r = -0.46, P INULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPF PAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function. © 2018 by the American Diabetes Association.

SUITABILITY OF VISCERAL ADIPOSITY INDEX AS A MARKER FOR CARDIOMETABOLIC RISKS IN JORDANIAN ADULTS.

Science.gov (United States)

Numan Ahmad, Mousa; Halim Haddad, Fares

2015-12-01

visceral adiposity index (VAI) has recently been proposed as a predictor of cardiometabolic risk, but its usefulness has not been confirmed. to evaluate the association between VAI and conventional adiposity and cardiometabolic risk indices and examine VAI risk predictive ability and compare it with other adiposity indices. a total of 1 622 Jordanian adults, 686 men and 936 women, aged 20-80 years were included this study. VAI, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR) were examined and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting serum glucose (FSG), systolic (SBP), and diastolic (DBP) blood pressure were determined. Associations and age-and gender specific distribution and differences were evaluated. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used for risk predictive ability comparison. VAI of women (6.82±6.43) was higher than of men (4.15±4.62). VAI severity increased with age in a dose-response trend (padiposity and cardiometabolic indices. VAI markedly associated with TG, HDL-C, FSG, SBP and DBP or WHR, WC, WHtR and BMI in respective order of correlation potency for cardiometabolic or adiposity risk indices. In men and women respectively, the largest AUC was for VAI (0.79 vs. 0.77), followed by WHR (0.73 vs. 0.75), WC (0.69 vs. 0.74), WHtR (0.65 vs. 0.71) and BMI (0.53 vs. 0.51). the findings suggest that VAI potentially associates with cardiometabolic risks and proves to be superior to other adiposity indices in predicting such risk. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Defining the identity of human adipose-derived mesenchymal stem cells.

Science.gov (United States)

Montelatici, Elisa; Baluce, Barbara; Ragni, Enrico; Lavazza, Cristiana; Parazzi, Valentina; Mazzola, Riccardo; Cantarella, Giovanna; Brambilla, Massimiliano; Giordano, Rosaria; Lazzari, Lorenza

2015-02-01

Adipose-derived mesenchymal stem cells (ADMSCs) are an ideal population for regenerative medical application. Both the isolation procedure and the culturing conditions are crucial steps, since low yield can limit further cell therapies, especially when minimal adipose tissue harvests are available for cell expansion. To date, a standardized procedure encompassing both isolation sites and expansion methods is missing, thus making the choice of the most appropriate conditions for the preparation of ADMSCs controversial, especially in view of the different applications needed. In this study, we compared the effects of three different commercial media (DMEM, aMEM, and EGM2), routinely used for ADMSCs expansion, and two supplements, FBS and human platelet lysate, recently proven to be an effective alternative to prevent xenogeneic antibody transfer and immune alloresponse in the host. Notably, all the conditions resulted in being safe for ADMSCs isolation and expansion with platelet lysate supplementation giving the highest isolation and proliferation rates, together with a commitment for osteogenic lineage. Then, we proved that the high ADMSC hematopoietic supportive potential is performed through a constant and abundant secretion of both GCSF and SCF. In conclusion, this study further expands the knowledge on ADMSCs, defining their identity definition and offers potential options for in vitro protocols for clinical production, especially related to HSC expansion without use of exogenous cytokines or genetic modifications.

Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

DEFF Research Database (Denmark)

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

2011-01-01

Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxi...

Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

Science.gov (United States)

Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

2007-02-13

Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes

Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

Science.gov (United States)

Feitosa, Mary F.; Barata, Llilda; Chu, Audrey Y.; Mahajan, Anubha; Hadley, David; Xue, Luting; Workalemahu, Tsegaselassie; den Hoed, Marcel; Ahluwalia, Tarunveer S.; Qi, Qibin; Ngwa, Julius S.; Quaye, Lydia; Eicher, John D.; Hayes, James E.; Cornelis, Marilyn; Kutalik, Zoltan; Lim, Elise; Luan, Jian’an; Huffman, Jennifer E.; Zhang, Weihua; Zhao, Wei; Griffin, Paula J.; Haller, Toomas; Ahmad, Shafqat; Marques-Vidal, Pedro M.; Bien, Stephanie; Yengo, Loic; Teumer, Alexander; Smith, Albert Vernon; Kumari, Meena; Harder, Marie Neergaard; Justesen, Johanne Marie; Kleber, Marcus E.; Hollensted, Mette; Lohman, Kurt; Rivera, Natalia V.; Whitfield, John B.; Zhao, Jing Hua; Stringham, Heather M.; Lyytikäinen, Leo-Pekka; Huppertz, Charlotte; Willemsen, Gonneke; Peyrot, Wouter J.; Wu, Ying; Kristiansson, Kati; Demirkan, Ayse; Fornage, Myriam; Hassinen, Maija; Bielak, Lawrence F.; Cadby, Gemma; Tanaka, Toshiko; Mägi, Reedik; van der Most, Peter J.; Jackson, Anne U.; Bragg-Gresham, Jennifer L.; Vitart, Veronique; Marten, Jonathan; Navarro, Pau; Bellis, Claire; Pasko, Dorota; Johansson, Åsa; Snitker, Søren; Cheng, Yu-Ching; Eriksson, Joel; Lim, Unhee; Aadahl, Mette; Adair, Linda S.; Amin, Najaf; Balkau, Beverley; Auvinen, Juha; Beilby, John; Bergman, Richard N.; Bergmann, Sven; Bertoni, Alain G.; Blangero, John; Bonnefond, Amélie; Bonnycastle, Lori L.; Borja, Judith B.; Brage, Søren; Busonero, Fabio; Buyske, Steve; Campbell, Harry; Chines, Peter S.; Collins, Francis S.; Corre, Tanguy; Smith, George Davey; Delgado, Graciela E.; Dueker, Nicole; Dörr, Marcus; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Faul, Jessica D.; Fu, Mao; Færch, Kristine; Gieger, Christian; Gläser, Sven; Gong, Jian; Gordon-Larsen, Penny; Grallert, Harald; Grammer, Tanja B.; Grarup, Niels; van Grootheest, Gerard; Harald, Kennet; Hastie, Nicholas D.; Havulinna, Aki S.; Hernandez, Dena; Hindorff, Lucia; Hocking, Lynne J.; Holmens, Oddgeir L.; Holzapfel, Christina; Hottenga, Jouke Jan; Huang, Jie; Huang, Tao; Hui, Jennie; Huth, Cornelia; Hutri-Kähönen, Nina; James, Alan L.; Jansson, John-Olov; Jhun, Min A.; Juonala, Markus; Kinnunen, Leena; Koistinen, Heikki A.; Kolcic, Ivana; Komulainen, Pirjo; Kuusisto, Johanna; Kvaløy, Kirsti; Kähönen, Mika; Lakka, Timo A.; Launer, Lenore J.; Lehne, Benjamin; Lindgren, Cecilia M.; Lorentzon, Mattias; Luben, Robert; Marre, Michel; Milaneschi, Yuri; Monda, Keri L.; Montgomery, Grant W.; De Moor, Marleen H. M.; Mulas, Antonella; Müller-Nurasyid, Martina; Musk, A. W.; Männikkö, Reija; Männistö, Satu; Narisu, Narisu; Nauck, Matthias; Nettleton, Jennifer A.; Nolte, Ilja M.; Oldehinkel, Albertine J.; Olden, Matthias; Ong, Ken K.; Padmanabhan, Sandosh; Paternoster, Lavinia; Perez, Jeremiah; Perola, Markus; Peters, Annette; Peters, Ulrike; Peyser, Patricia A.; Prokopenko, Inga; Puolijoki, Hannu; Raitakari, Olli T.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rawal, Rajesh; Ridker, Paul M.; Rose, Lynda M.; Rudan, Igor; Sarti, Cinzia; Sarzynski, Mark A.; Savonen, Kai; Scott, William R.; Sanna, Serena; Shuldiner, Alan R.; Sidney, Steve; Silbernagel, Günther; Smith, Blair H.; Smith, Jennifer A.; Snieder, Harold; Stančáková, Alena; Sternfeld, Barbara; Swift, Amy J.; Tammelin, Tuija; Tan, Sian-Tsung; Thorand, Barbara; Thuillier, Dorothée; Vandenput, Liesbeth; Vestergaard, Henrik; van Vliet-Ostaptchouk, Jana V.; Vohl, Marie-Claude; Völker, Uwe; Waeber, Gérard; Walker, Mark; Wild, Sarah; Wong, Andrew; Wright, Alan F.; Zillikens, M. Carola; Zubair, Niha; Haiman, Christopher A.; Lemarchand, Loic; Gyllensten, Ulf; Ohlsson, Claes; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Pérusse, Louis; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Cucca, Francesco; Hveem, Kristian; Hartman, Catharina A.; Tönjes, Anke; Bandinelli, Stefania; Palmer, Lyle J.; Kardia, Sharon L. R.; Rauramaa, Rainer; Sørensen, Thorkild I. A.; Tuomilehto, Jaakko; Salomaa, Veikko; Penninx, Brenda W. J. H.; de Geus, Eco J. C.; Boomsma, Dorret I.; Lehtimäki, Terho; Mangino, Massimo; Laakso, Markku; Bouchard, Claude; Martin, Nicholas G.; Kuh, Diana; Liu, Yongmei; Linneberg, Allan; März, Winfried; Strauch, Konstantin; Kivimäki, Mika; Harris, Tamara B.; Gudnason, Vilmundur; Völzke, Henry; Qi, Lu; Järvelin, Marjo-Riitta; Chambers, John C.; Kooner, Jaspal S.; Froguel, Philippe; Kooperberg, Charles; Vollenweider, Peter; Hallmans, Göran; Hansen, Torben; Pedersen, Oluf; Metspalu, Andres; Wareham, Nicholas J.; Langenberg, Claudia; Weir, David R.; Porteous, David J.; Boerwinkle, Eric; Chasman, Daniel I.; Abecasis, Gonçalo R.; McCarthy, Mark I.; Frayling, Timothy M.; O’Connell, Jeffrey R.; van Duijn, Cornelia M.; Boehnke, Michael; Heid, Iris M.; Mohlke, Karen L.; Fox, Caroline S.; Hirschhorn, Joel N.; Johnson, Andrew D.; Borecki, Ingrid B.; Franks, Paul W.; North, Kari E.; Cupples, L. Adrienne; Loos, Ruth J. F.; Kilpeläinen, Tuomas O.

2017-01-01

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery. PMID:28448500

Waist Circumference, Body Mass Index, and Other Measures of Adiposity in Predicting Cardiovascular Disease Risk Factors among Peruvian Adults

OpenAIRE

Knowles, K. M.; Paiva, L. L.; Sanchez, S. E.; Revilla, L.; Lopez, T.; Yasuda, M. B.; Yanez, N. D.; Gelaye, B.; Williams, M. A.

2011-01-01

Objectives. To examine the extent to which measures of adiposity can be used to predict selected components of metabolic syndrome (MetS) and elevated C-reactive protein (CRP). Methods. A total of 1,518 Peruvian adults were included in this study. Waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHtR), and visceral adiposity index (VAI) were examined. The prevalence of each MetS component was determined according to tertiles of each anthropometric mea...

Waist Circumference, Body Mass Index, and Other Measures of Adiposity in Predicting Cardiovascular Disease Risk Factors among Peruvian Adults

Directory of Open Access Journals (Sweden)

K. M. Knowles

2011-01-01

Full Text Available Objectives. To examine the extent to which measures of adiposity can be used to predict selected components of metabolic syndrome (MetS and elevated C-reactive protein (CRP. Methods. A total of 1,518 Peruvian adults were included in this study. Waist circumference (WC, body mass index (BMI, waist-hip ratio (WHR, waist-height ratio (WHtR, and visceral adiposity index (VAI were examined. The prevalence of each MetS component was determined according to tertiles of each anthropometric measure. ROC curves were used to evaluate the extent to which measures of adiposity can predict cardiovascular risk. Results. All measures of adiposity had the strongest correlation with triglyceride concentrations (TG. For both genders, as adiposity increased, the prevalence of Mets components increased. Compared to individuals with low-BMI and low-WC, men and women with high-BMI and high- WC had higher odds of elevated fasting glucose, blood pressure, TG, and reduced HDL, while only men in this category had higher odds of elevated CRP. Overall, the ROCs showed VAI, WC, and WHtR to be the best predictors for individual MetS components. Conclusions. The results of our study showed that measures of adiposity are correlated with cardiovascular risk although no single adiposity measure was identified as the best predictor for MetS.

Differentiation of Human Adipose Derived Stem Cells into Smooth Muscle Cells Is Modulated by CaMKIIγ

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Kaisaier Aji

2016-01-01

Full Text Available The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII is known to participate in maintenance and switches of smooth muscle cell (SMC phenotypes. However, which isoform of CaMKII is involved in differentiation of adult mesenchymal stem cells into contractile SMCs remains unclear. In the present study, we detected γ isoform of CaMKII in differentiation of human adipose derived stem cells (hASCs into SMCs that resulted from treatment with TGF-β1 and BMP4 in combination for 7 days. The results showed that CaMKIIγ increased gradually during differentiation of hASCs as determined by real-time PCR and western blot analysis. The siRNA-mediated knockdown of CaMKIIγ decreased the protein levels and transcriptional levels of smooth muscle contractile markers (a-SMA, SM22a, calponin, and SM-MHC, while CaMKIIγ overexpression increases the transcriptional and protein levels of smooth muscle contractile markers. These results suggested that γ isoform of CaMKII plays a significant role in smooth muscle differentiation of hASCs.

Adipose Derived Stromal Cell (ADSC) Injections for Pain Management of Osteoarthritis in the Human Knee Joint.

Science.gov (United States)

Fodor, Peter B; Paulseth, Stephen G

2016-02-01

This safety and feasibility study used autologous adipose-derived stromal vascular cells (the stromal vascular fraction [SVF] of adipose tissue), to treat 8 osteoarthritic knees in 6 patients of grade I to III (K-L scale) with initial pain of 4 or greater on a 10-point Visual Analog Scale (VAS). The primary objective of the study was evaluation of the safety of intra-articular injection of SVF. The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees. Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate, resuspension in 3 mL of Lactated Ringer's Solution, and injection directly into the intra-articular space of the knee, with a mean of 14.1 million viable, nucleated SVF cells per knee. Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the VAS pain scale, range of motion (ROM), timed up-and-go (TUG), and MRI. No infections, acute pain flares, or other adverse events were reported. At 3-months postoperative, there was a statistically significant improvement in WOMAC and VAS scores (P knee pain. Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee. LEVEL OF EVIDENCE 4: Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

International Nuclear Information System (INIS)

Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

2013-01-01

This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH 2 ), carboxyl (-COOH) and methyl (-CH 3 ), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH 2 ) can absorb more proteins than these modified with more hydrophobic functional group (-CH 3 ). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH 2 modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH 3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Liu, Xujie [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Feng, Qingling, E-mail: biomater@mail.tsinghua.edu.cn [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Bachhuka, Akash [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); Vasilev, Krasimir [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); School of Advanced Manufacturing, University of South Australia, Mawson Lakes 5095 (Australia)

2013-04-01

This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH{sub 2}), carboxyl (-COOH) and methyl (-CH{sub 3}), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH{sub 2}) can absorb more proteins than these modified with more hydrophobic functional group (-CH{sub 3}). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH{sub 2} modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH{sub 3} modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

Mesenchymal stem cells derived from adipose tissue vs bone marrow: in vitro comparison of their tropism towards gliomas.

Directory of Open Access Journals (Sweden)

Courtney Pendleton

Full Text Available INTRODUCTION: Glioblastoma is the most common primary malignant brain tumor, and is refractory to surgical resection, radiation, and chemotherapy. Human mesenchymal stem cells (hMSC may be harvested from bone marrow (BMSC and adipose (AMSC tissue. These cells are a promising avenue of investigation for the delivery of adjuvant therapies. Despite extensive research into putative mechanisms for the tumor tropism of MSCs, there remains no direct comparison of the efficacy and specificity of AMSC and BMSC tropism towards glioma. METHODS: Under an IRB-approved protocol, intraoperative human Adipose MSCs (hAMSCs were established and characterized for cell surface markers of mesenchymal stem cell origin in conjunction with the potential for tri-lineage differentiation (adipogenic, chondrogenic, and osteogenic. Validated experimental hAMSCs were compared to commercially derived hBMSCs (Lonza and hAMSCs (Invitrogen for growth responsiveness and glioma tropism in response to glioma conditioned media obtained from primary glioma neurosphere cultures. RESULTS: Commercial and primary culture AMSCs and commercial BMSCs demonstrated no statistically significant difference in their migration towards glioma conditioned media in vitro. There was statistically significant difference in the proliferation rate of both commercial AMSCs and BMSCs as compared to primary culture AMSCs, suggesting primary cultures have a slower growth rate than commercially available cell lines. CONCLUSIONS: Adipose- and bone marrow-derived mesenchymal stem cells have similar in vitro glioma tropism. Given the well-documented ability to harvest larger numbers of AMSCs under local anesthesia, adipose tissue may provide a more efficient source of MSCs for research and clinical applications, while minimizing patient morbidity during cell harvesting.

Human adipose-derived mesenchymal stem cells as a new model of spinal and bulbar muscular atrophy.

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Marta Dossena

Full Text Available Spinal and bulbar muscular atrophy (SBMA or Kennedy's disease is an X-linked CAG/polyglutamine expansion motoneuron disease, in which an elongated polyglutamine tract (polyQ in the N-terminal androgen receptor (ARpolyQ confers toxicity to this protein. Typical markers of SBMA disease are ARpolyQ intranuclear inclusions. These are generated after the ARpolyQ binds to its endogenous ligands, which promotes AR release from chaperones, activation and nuclear translocation, but also cell toxicity. The SBMA mouse models developed so far, and used in preclinical studies, all contain an expanded CAG repeat significantly longer than that of SBMA patients. Here, we propose the use of SBMA patients adipose-derived mesenchymal stem cells (MSCs as a new human in vitro model to study ARpolyQ toxicity. These cells have the advantage to express only ARpolyQ, and not the wild type AR allele. Therefore, we isolated and characterized adipose-derived MSCs from three SBMA patients (ADSC from Kennedy's patients, ADSCK and three control volunteers (ADSCs. We found that both ADSCs and ADSCKs express mesenchymal antigens, even if only ADSCs can differentiate into the three typical cell lineages (adipocytes, chondrocytes and osteocytes, whereas ADSCKs, from SBMA patients, showed a lower growth potential and differentiated only into adipocyte. Moreover, analysing AR expression on our mesenchymal cultures we found lower levels in all ADSCKs than ADSCs, possibly related to negative pressures exerted by toxic ARpolyQ in ADSCKs. In addition, with proteasome inhibition the ARpolyQ levels increased specifically in ADSCKs, inducing the formation of HSP70 and ubiquitin positive nuclear ARpolyQ inclusions. Considering all of this evidence, SBMA patients adipose-derived MSCs cultures should be considered an innovative in vitro human model to understand the molecular mechanisms of ARpolyQ toxicity and to test novel therapeutic approaches in SBMA.

Adipose derived mesenchymal stem cells – Their osteogenicity and osteoblast in vitro mineralization on titanium granule carriers

DEFF Research Database (Denmark)

Dahl, Morten; Syberg, Susanne; Jørgensen, Niklas Rye

2013-01-01

Adipose derived mesenchymal stem cells (ADMSCs) may be osteogenic, may generate neoangiogenisis and may be progenitors for differentiated osteoblast mineralization. Titanium granules may be suitable as carriers for these cells. The aim was to demonstrate the osteogenic potential of ADMSCs...

Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells

OpenAIRE

Eirin, Alfonso; Zhu, Xiang-Yang; Puranik, Amrutesh S.; Woollard, John R.; Tang, Hui; Dasari, Surendra; Lerman, Amir; van Wijnen, Andre J.; Lerman, Lilach O.

2017-01-01

Background Mesenchymal stromal/stem cell (MSC) transplantation is a promising therapy for tissue regeneration. Extracellular vesicles (EVs) released by MSCs act as their paracrine effectors by delivering proteins and genetic material to recipient cells. To assess how their cargo mediates biological processes that drive their therapeutic effects, we integrated miRNA, mRNA, and protein expression data of EVs from porcine adipose tissue-derived MSCs. Methods Simultaneous expression profiles of m...

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.

Science.gov (United States)

Fraser, John K; Hicok, Kevin C; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution ® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

Physical activity as a mediator of the associations between neighborhood walkability and adiposity in Belgian adults.

Science.gov (United States)

Van Dyck, Delfien; Cerin, Ester; Cardon, Greet; Deforche, Benedicte; Sallis, James F; Owen, Neville; de Bourdeaudhuij, Ilse

2010-09-01

This study examined whether physical activity (PA) and sedentary behavior mediated the relationship of neighborhood walkability with two measures of adiposity: body mass index (BMI) and waist-to-height ratio (WHTR). Twenty-four neighborhoods in Ghent, Belgium were selected, stratified by objectively assessed walkability and by socio-economic status. Participants (1200 adults aged 20-65 years) completed the International Physical Activity Questionnaire and wore an accelerometer for 7 days. Weight and height were self-reported and waist circumference was objectively measured. Accelerometer-assessed moderate-to-vigorous PA and self-reported cycling for transport mediated the associations of walkability with BMI and WHTR. Moreover, walking for transport and recreational walking significantly mediated the relationship between walkability and BMI. Sedentary behavior did not mediate associations of walkability with BMI or WHTR. These findings suggest that PA, but not sedentary behavior, is a mechanism by which walkability may affect adults' adiposity. Planning for neighborhoods to be high in walkability could have favorable effects on physical activity and weight status. Copyright 2010 Elsevier Ltd. All rights reserved.

Platelet-Rich Plasma Influences Expansion and Paracrine Function of Adipose-Derived Stromal Cells in a Dose-Dependent Fashion

NARCIS (Netherlands)

Willemsen, Joep C. N.; Spiekman, Maroesjka; Stevens, H. P. Jeroen; van der Lei, Berend; Harmsen, Martin C.

Background: Lipofilling is a treatment modality to restore tissue volume. Both platelet-rich plasma and adipose-derived stromal cells have been reported to augment the efficacy of lipofilling, yet results are not conclusive. The authors hypothesized that the variation reported in literature is

MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

DEFF Research Database (Denmark)

Yin, Hang; Pasut, Alessandra; Soleimani, Vahab D

2013-01-01

Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells...... (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism...... of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels...

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

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T.C. Peixoto

2018-04-01

Full Text Available Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

Science.gov (United States)

Peixoto, T C; Moura, E G; Oliveira, E; Younes-Rapozo, V; Soares, P N; Rodrigues, V S T; Santos, T R; Peixoto-Silva, N; Carvalho, J C; Calvino, C; Conceição, E P S; Guarda, D S; Claudio-Neto, S; Manhães, A C; Lisboa, P C

2018-01-01

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Osteogenic capability of autologous rabbit adipose-derived stromal cells in repairing calvarial defects

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CHENG Shao-wen

2012-02-01

Full Text Available 【Abstract】Objective: To evaluate the in vitro and in vivo osteogenic capability of adipose-derived stromal cells (ASCs. Methods: ASCs were isolated from New Zealand white rabbits and determined by alkaline phosphatase (ALP staining, von Kossa staining and alizarin red staining. Some specific markers of osteogenic differentiation, including ALP, osteocalcin (OCN, osteopontin (OPN were examined by reverse transcription-polymerase chain reaction (RT-PCR. In vivo, demineralized bone matrix (DBM-ASCs composites were implanted into the rabbit calvarial defects created at each side of the longitudinal midline. After 6 weeks, histologic properties of the transplants were analyzed. Results: ASCs were successfully induced into osteogenesis. ALP staining, von Kossa staining and alizarin red staining showed positive results. The expressions of ALP, OCN and OPN were detected in ASCs after cultivation in osteogenic medium. Extensive new bone was observed in the defects transplanted with DBM-ASCs composites. Conclusion: ASCs have the potential to differentiate into osteogenic lineage and DBM-ASCs constructs are a promising method for regeneration in bone defects. Key words: Adipose tissue; Bone regeneration; Osteogenesis

Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis

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Maria Elena Falomo

2015-01-01

Full Text Available Endometriosis is a degenerative process due to a chronic inflammatory damage leading to extracellular matrix components deposition and glandular fibrosis. It is known that mesenchymal stem cells secrete a wide range of bioactive molecules, some of them modulating the immune inflammatory response, and others providing regeneration and remodeling of injured tissue. We have performed in vitro experiments in order to analyze the capability of allogenic equine adipose-derived stem cells (ADSCs to infiltrate mares’ endometrial tissues and to stimulate the expression of cytokines and metallopeptidases. Differences in the biologic response to the exposure to ADSCs between pathological and healthy endometrial tissue have been identified. These results could challenge researchers to progress forward with future studies for the development of a biological therapy with a possible application in translational medicine.

Functional polyaniline nanofibre mats for human adipose-derived stem cell proliferation and adhesion

International Nuclear Information System (INIS)

Abdul Rahman, Norizah; Feisst, Vaughan; Dickinson, Michelle E.; Malmström, Jenny; Dunbar, P. Rod; Travas-Sejdic, Jadranka

2013-01-01

Conductive polymer poly(aniline-co-m-aminobenzoic acid) (P(ANI-co-m-ABA)) and polyaniline (PANI) were blended with a biodegradable, biocompatible polymer, poly(L-lactic acid) and were electrospun into nanofibres to investigate their potential application as a scaffold for human adipose-derived stem cells (hASCs). These polymers, in both conductive and non-conductive form, were electrospun with average fibre diameters of less than 400 nm. Novel nanoindentation results obtained on the individual nanofibres revealed that the elastic moduli of the nanofibres are much higher at the surface (4–10 GPa, h max max >75 nm). The composite nanofibres showed great promise as a scaffold for hASCs as they supported the cell adhesion and proliferation. After 1 week of cell culture hASCs were well spread on the substrates with abundant focal adhesions. The electrospun mats provide the cells with comparably stiff, sub-micron sized fibres as anchoring points on a substrate of high porosity. The conductive nature of these composite nanofibres offers exciting opportunities for electrical stimulation of the cells. - Highlights: ► Polyaniline and its copolymer's nanofibres were prepared by electrospinning. ► The elastic modulus of a single polyaniline composite nanofibres were determined. ► Elastic moduli of the nanofibres are much higher at the surface than the inner core. ► The electrospun mats supported the cell adhesion and proliferation. ► The nanofibres show great promise as a scaffold for adipose derived stem cells

Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells : a controlled experimental trial

NARCIS (Netherlands)

Geburek, Florian; Roggel, Florian; van Schie, Hans T M; Beineke, Andreas; Estrada, Roberto; Weber, Kathrin; Hellige, Maren; Rohn, Karl; Jagodzinski, Michael; Welke, Bastian; Hurschler, Christof; Conrad, Sabine; Skutella, Thomas; van de Lest, Chris; van Weeren, René; Stadler, Peter M

2017-01-01

BACKGROUND: Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in

Uniaxial cyclic strain enhances adipose-derived stem cell fusion with skeletal myocytes

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Andersen, Jens Isak; Juhl, Morten; Nielsen, Thøger; Emmersen, Jeppe; Fink, Trine; Zachar, Vladimir; Pennisi, Cristian Pablo, E-mail: cpennisi@hst.aau.dk

2014-07-25

Highlights: • Uniaxial cyclic tensile strain (CTS) applied to ASCs alone or in coculture with myogenic precursors. • CTS promoted the formation of a highly ordered array of parallel ASCs. • Without biochemical supplements, CTS did not support advanced myogenic differentiation of ASCs. • Mechanical stimulation of cocultures boosted fusion of ASCs with skeletal myoblasts. - Abstract: Although adult muscle tissue possesses an exceptional capacity for regeneration, in the case of large defects, the restoration to original state is not possible. A well-known source for the de novo regeneration is the adipose-derived stem cells (ASCs), which can be readily isolated and have been shown to have a broad differentiation and regenerative potential. In this work, we employed uniaxial cyclic tensile strain (CTS), to mechanically stimulate human ASCs to participate in the formation skeletal myotubes in an in vitro model of myogenesis. The application of CTS for 48 h resulted in the formation of a highly ordered array of parallel ASCs, but failed to support skeletal muscle terminal differentiation. When the same stimulation paradigm was applied to cocultures with mouse skeletal muscle myoblasts, the percentage of ASCs contributing to the formation of myotubes significantly exceeded the levels reported in the literature hitherto. In perspective, the mechanical strain may be used to increase the efficiency of incorporation of ASCs in the skeletal muscles, which could be found useful in diverse traumatic or pathologic scenarios.

A Weight-Loss Diet Including Coffee-Derived Mannooligosaccharides Enhances Adipose Tissue Loss in Overweight Men but Not Women

Science.gov (United States)

St-Onge, Marie-Pierre; Salinardi, Taylor; Herron-Rubin, Kristin; Black, Richard M.

2013-01-01

Mannooligosaccharides (MOS), extracted from coffee, have been shown to promote a decrease in body fat when consumed as part of free-living, weight-maintaining diets. Our objective was to determine if MOS consumption (4 g/day), in conjunction with a weight-loss diet, would lead to greater reductions in adipose tissue compartments than placebo. We conducted a double-blind, placebo-controlled weight-loss study in which 60 overweight men and women consumed study beverages and received weekly group counseling for 12 weeks. Weight and blood pressure were measured weekly, and adipose tissue distribution was assessed at baseline and at end point using magnetic resonance imaging. A total of 54 subjects completed the study. Men consuming the MOS beverage had greater loss of body weight than men consuming the Placebo beverage (−6.0 ± 0.6% vs. −2.3 ± 0.5%, respectively, P coffee-derived MOS to a weight-loss diet enhanced both weight and adipose tissue losses in men, suggesting a potential functional use of MOS for weight management and improvement in adipose tissue distribution. More studies are needed to investigate the apparent gender difference in response to MOS consumption. PMID:21938072

Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells: an in Vitro Study

NARCIS (Netherlands)

Sukho, P. (Panithi); J. Kirpensteijn (Jolle); Hesselink, J.W. (Jan Willem); G.J.V.M. van Osch (Gerjo); F. Verseijden (Femke); Y.M. Bastiaansen-Jenniskens (Yvonne)

2017-01-01

textabstractAdipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were

Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

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Angelou Valerie

2016-01-01

Full Text Available Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group. We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments.

Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

Science.gov (United States)

Vassiliki, Kalodimou; Irini, Messini; Nikolaos, Psychalakis; Karampela, Eleftheria; Apostolos, Papalois

2016-01-01

Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments. PMID:26933440

Amniotic membrane seeded with mesenchymal adipose-derived stem cell for coverage of wound in third degree burn: An experimental study

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Mohammad Javad Fatemi

2014-09-01

Conclusion: Acellular amnion seeded with adipose-derived stem cell can result in faster wound healing and better histopathology characteristic. The amnion as a scaffold and the fat derived stem cells as healing accelerator are recommended for coverage of the 3rd degree burn wounds after excision and it may reduce the need for skin graft.

Extract of mouse embryonic stem cells induces the expression of pluripotency genes in human adipose tissue-derived stem cells.

Science.gov (United States)

Salehi, Paria Motamen; Foroutan, Tahereh; Javeri, Arash; Taha, Masoumeh Fakhr

2017-11-01

In some previous studies, the extract of embryonic carcinoma cells (ECCs) and embryonic stem cells (ESCs) have been used to reprogram somatic cells to more dedifferentiated state. The aim of this study was to investigate the effect of mouse ESCs extract on the expression of some pluripotency markers in human adipose tissue-derived stem cells (ADSCs). Human ADSCs were isolated from subcutaneous abdominal adipose tissue and characterized by flow cytometric analysis for the expression of some mesenchymal stem cell markers and adipogenic and osteogenic differentiation. Frequent freeze-thaw technique was used to prepare cytoplasmic extract of ESCs. Plasma membranes of the ADSCs were reversibly permeabilized by streptolysin-O (SLO). Then the permeabilized ADSCs were incubated with the ESC extract and cultured in resealing medium. After reprogramming, the expression of some pluripotency genes was evaluated by RT-PCR and quantitative real-time PCR (qPCR) analyses. Third-passaged ADSCs showed a fibroblast-like morphology and expressed mesenchymal stem cell markers. They also showed adipogenic and osteogenic differentiation potential. QPCR analysis revealed a significant upregulation in the expression of some pluripotency genes including OCT4 , SOX2 , NANOG , REX1 and ESG1 in the reprogrammed ADSCs compared to the control group. These findings showed that mouse ESC extract can be used to induce reprogramming of human ADSCs. In fact, this method is applicable for reprogramming of human adult stem cells to a more pluripotent sate and may have a potential in regenerative medicine.

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

Science.gov (United States)

Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

2016-05-01

Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.

Adipose-Derived Stem Cells in Novel Approaches to Breast Reconstruction: Their Suitability for Tissue Engineering and Oncological Safety.

Science.gov (United States)

O'Halloran, Niamh; Courtney, Donald; Kerin, Michael J; Lowery, Aoife J

2017-01-01

Adipose-derived stem cells (ADSCs) are rapidly becoming the gold standard cell source for tissue engineering strategies and hold great potential for novel breast reconstruction strategies. However, their use in patients with breast cancer is controversial and their oncological safety, particularly in relation to local disease recurrence, has been questioned. In vitro, in vivo, and clinical studies using ADSCs report conflicting data on their suitability for adipose tissue regeneration in patients with cancer. This review aims to provide an overview of the potential role for ADSCs in breast reconstruction and to examine the evidence relating to the oncologic safety of their use in patients with breast cancer.

Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells.

Science.gov (United States)

Yoshimura, Kotaro; Sato, Katsujiro; Aoi, Noriyuki; Kurita, Masakazu; Inoue, Keita; Suga, Hirotaka; Eto, Hitomi; Kato, Harunosuke; Hirohi, Toshitsugu; Harii, Kiyonori

2008-09-01

Lipoinjection is a promising treatment, but its efficacy in recontouring facial lipoatrophy remains to be established. The objective was to evaluate the efficacy and adverse effects of lipoinjection and supplementation of adipose-derived stem/stromal cells (ASCs) to adipose grafts. To overcome drawbacks of autologous lipoinjection, we have developed a novel strategy called cell-assisted lipotransfer (CAL). In CAL, stromal vascular fraction containing ASCs was freshly isolated from half of an aspirated fat sample and attached to the other half of aspirated fat sample with the fat acting as a scaffold. This process converts relatively ASC-poor aspirated fat into ASC-rich fat. We performed conventional lipoinjection (non-CAL; n=3) or CAL (n=3) on six patients with facial lipoatrophy due to lupus profundus or Parry-Romberg syndrome. All patients obtained improvement in facial contour, but the CAL group had a better clinical improvement score than did the non-CAL patients, although the difference did not reach statistical significance (p=.11). Adipose necrosis was found in one non-CAL case who took perioperative oral corticosteroids. Our results suggest that CAL is both effective and safe and potentially superior to conventional lipoinjection for facial recontouring. The authors have indicated no significant interest with commercial supporters.

Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells : an in Vitro Study

NARCIS (Netherlands)

Sukho, Panithi; Kirpensteijn, Jolle; Hesselink, Jan Willem; van Osch, Gerjo J V M; Verseijden, Femke; Bastiaansen-Jenniskens, Yvonne M

Adipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were cultured in 8000

Molecular Validation of Chondrogenic Differentiation and Hypoxia Responsiveness of Platelet-Lysate Expanded Adipose Tissue–Derived Human Mesenchymal Stromal Cells

NARCIS (Netherlands)

Galeano-Garces, Catalina; Camilleri, Emily T.; Riester, Scott M.; Dudakovic, Amel; Larson, Dirk R.; Qu, Wenchun; Smith, Jay; Dietz, Allan B.; Im, Hee-Jeong; Krych, Aaron J.; Larson, A. Noelle; Karperien, Marcel; van Wijnen, Andre J.

2017-01-01

Objective: To determine the optimal environmental conditions for chondrogenic differentiation of human adipose tissue–derived mesenchymal stromal/stem cells (AMSCs). In this investigation we specifically investigate the role of oxygen tension and 3-dimensional (3D) culture systems. Design: Both

Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

Science.gov (United States)

Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

2013-05-01

Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. Copyright © 2012 Wiley Periodicals, Inc.

Case Reports of Adipose-derived Stem Cell Therapy for Nasal Skin Necrosis after Filler Injection

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Ha Min Sung

2012-01-01

Full Text Available With the gradual increase of cases using fillers, cases of patients treated by non-medical professionals or inexperienced physicians resulting in complications are also increasing. We herein report 2 patients who experienced acute complications after receiving filler injections and were successfully treated with adipose-derived stem cell (ADSCs therapy. Case 1 was a 23-year-old female patient who received a filler (Restylane injection in her forehead, glabella, and nose by a non-medical professional. The day after her injection, inflammation was observed with a 3×3 cm skin necrosis. Case 2 was a 30-year-old woman who received a filler injection of hyaluronic acid gel (Juvederm on her nasal dorsum and tip at a private clinic. She developed erythema and swelling in the filler-injected area A solution containing ADSCs harvested from each patient's abdominal subcutaneous tissue was injected into the lesion at the subcutaneous and dermis levels. The wounds healed without additional treatment. With continuous follow-up, both patients experienced only fine linear scars 6 months postoperatively. By using adipose-derived stem cells, we successfully treated the acute complications of skin necrosis after the filler injection, resulting in much less scarring, and more satisfactory results were achieved not only in wound healing, but also in esthetics.

Cytotoxicity assessment of adipose-derived mesenchymal stem cells on synthesized biodegradable Mg-Zn-Ca alloys

Energy Technology Data Exchange (ETDEWEB)

Fazel Anvari-Yazdi, Abbas [Department of Biomedical Engineering, Materials and Biomaterials Research Center (MBMRC), Tehran, IR (Iran, Islamic Republic of); Tahermanesh, Kobra, E-mail: tahermanesh.k@iums.ac.ir [Endometriosis and Gynecologic Disorders Research Center, Department of Ob. & Gyn., Rasoul-e Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, IR (Iran, Islamic Republic of); Hadavi, Seyed Mohammad Mehdi [Materials and Energy Research Center (MERC), Karaj, IR (Iran, Islamic Republic of); Talaei-Khozani, Tahereh [Tissue Engineering Lab, Anatomy Department, School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, IR (Iran, Islamic Republic of); Razmkhah, Mahboobeh [Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, IR (Iran, Islamic Republic of); Abed, Seyedeh Mehr [School of Medicine, Yasuj University of Medical Sciences (YUMS), Yasuj, IR (Iran, Islamic Republic of); Mohtasebi, Maryam Sadat [Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, IR (Iran, Islamic Republic of)

2016-12-01

Magnesium (Mg)-based alloys have been extensively considered as biodegradable implant materials for orthopedic surgery. Mg and its alloys are metallic biomaterials that can degrade in the body and promote new bone formation. In this study, the corrosion behavior and cytotoxicity of Mg-Zn-Ca alloys are evaluated with adipose-derived mesenchymal stem cells (ASCs). Mg-2Zn and Mg-2Zn-xCa (x = 1, 2 and 3 wt.%) alloys were designated. Mg alloys were analyzed with scanning electron microscopy and potentiodynamic polarization. To understand the in-vitro biocompatibility and cytotoxicity of Mg-2Zn and Mg-2Zn-xCa alloys, ASCs were cultured for 24 and 72 h in contact with 10%, 50% and 100% extraction of all alloys prepared in DMEM. Cell cytotoxicity and viability of ASCs were examined by MTT assay. Alloying elements including Zn and Ca improved the corrosion resistance of alloys were compared with pure Mg. The cytotoxicity results showed that all alloys had no significant adverse effects on cell viability in 24 h. After 72 h, cell viability and proliferation increased in the cells exposed to pure Mg and Mg-2Zn-1Ca extracts. The release of Mg, Zn and Ca ions in culture media had no toxic impacts on ASCs viability and proliferation. Mg-2Zn-1Ca alloy can be suggested as a good candidate to be used in biomedical applications. - Highlights: • Short and long term corrosion behavior of Mg-Zn-Ca alloys studied • Viability and toxicity of Adipose-derived Stem cells studied with Mg-Zn-Ca alloys • Understanding the morphology of cultured adipose stem cells on Mg alloys • Stem cells on Mg-Zn-Ca alloys could proliferate and expand.

Cell kinetics, DNA integrity, differentiation, and lipid fingerprinting analysis of rabbit adipose-derived stem cells.

Science.gov (United States)

Barretto, Letícia Siqueira de Sá; Lessio, Camila; Sawaki e Nakamura, Ahy Natally; Lo Turco, Edson Guimarães; da Silva, Camila Gonzaga; Zambon, João Paulo; Gozzo, Fábio César; Pilau, Eduardo Jorge; de Almeida, Fernando Gonçalves

2014-10-01

Human adipose tissue has been described as a potential alternative reservoir for stem cells. Although studies have been performed in rabbits using autologous adipose-derived stem cells (ADSC), these cells have not been well characterized. The primary objectives of this study were to demonstrate the presence of adipose-derived stem cells isolated from rabbit inguinal fat pads and to characterize them through osteogenic and adipogenic in vitro differentiation and lipid fingerprinting analysis. The secondary objective was to evaluate cell behavior through growth kinetics, cell viability, and DNA integrity. Rabbit ADSCs were isolated to determine the in vitro growth kinetics and cell viability. DNA integrity was assessed by an alkaline Comet assay in passages 0 and 5. The osteogenic differentiation was evaluated by Von Kossa, and Alizarin Red S staining and adipogenic differentiation were assessed by Oil Red O staining. Lipid fingerprinting analyses of control, adipogenic, and osteogenic differentiated cells were performed by MALDI-TOF/MS. We demonstrate that rabbit ADSC have a constant growth rate at the early passages, with increased DNA fragmentation at or after passage 5. Rabbit ADSC viability was similar in passages 2 and 5 (90.7% and 86.6%, respectively), but there was a tendency to decreased cellular growth rate after passage 3. The ADSC were characterized by the expression of surface markers such as CD29 (67.4%) and CD44 (89.4%), using CD 45 (0.77%) as a negative control. ADSC from rabbits were successfully isolated form the inguinal region. These cells were capable to differentiate into osteogenic and adipogenic tissue when they were placed in inductive media. After each passage, there was a trend towards decreased cell growth. On the other hand, DNA fragmentation increased at each passage. ADSC had a different lipid profile when placed in control, adipogenic, or osteogenic media.

Cytotoxicity assessment of adipose-derived mesenchymal stem cells on synthesized biodegradable Mg-Zn-Ca alloys

International Nuclear Information System (INIS)

Fazel Anvari-Yazdi, Abbas; Tahermanesh, Kobra; Hadavi, Seyed Mohammad Mehdi; Talaei-Khozani, Tahereh; Razmkhah, Mahboobeh; Abed, Seyedeh Mehr; Mohtasebi, Maryam Sadat

2016-01-01

Magnesium (Mg)-based alloys have been extensively considered as biodegradable implant materials for orthopedic surgery. Mg and its alloys are metallic biomaterials that can degrade in the body and promote new bone formation. In this study, the corrosion behavior and cytotoxicity of Mg-Zn-Ca alloys are evaluated with adipose-derived mesenchymal stem cells (ASCs). Mg-2Zn and Mg-2Zn-xCa (x = 1, 2 and 3 wt.%) alloys were designated. Mg alloys were analyzed with scanning electron microscopy and potentiodynamic polarization. To understand the in-vitro biocompatibility and cytotoxicity of Mg-2Zn and Mg-2Zn-xCa alloys, ASCs were cultured for 24 and 72 h in contact with 10%, 50% and 100% extraction of all alloys prepared in DMEM. Cell cytotoxicity and viability of ASCs were examined by MTT assay. Alloying elements including Zn and Ca improved the corrosion resistance of alloys were compared with pure Mg. The cytotoxicity results showed that all alloys had no significant adverse effects on cell viability in 24 h. After 72 h, cell viability and proliferation increased in the cells exposed to pure Mg and Mg-2Zn-1Ca extracts. The release of Mg, Zn and Ca ions in culture media had no toxic impacts on ASCs viability and proliferation. Mg-2Zn-1Ca alloy can be suggested as a good candidate to be used in biomedical applications. - Highlights: • Short and long term corrosion behavior of Mg-Zn-Ca alloys studied • Viability and toxicity of Adipose-derived Stem cells studied with Mg-Zn-Ca alloys • Understanding the morphology of cultured adipose stem cells on Mg alloys • Stem cells on Mg-Zn-Ca alloys could proliferate and expand

Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

International Nuclear Information System (INIS)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

2011-01-01

Research highlights: → Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. → Irbesartan decreased white adipose tissue weight without affecting body weight. → DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. → Irbesartan increased adipocyte number in white adipose tissue. → Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPARγ agonistic action of an AT 1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: a novel mechanistic insight into progressive obesity.

Science.gov (United States)

Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin

2013-09-05

Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis*

OpenAIRE

Lai, Qing-guo; Sun, Shao-long; Zhou, Xiao-hong; Zhang, Chen-ping; Yuan, Kui-feng; Yang, Zhong-jun; Luo, Sheng-lei; Tang, Xiao-peng; Ci, Jiang-bo

2014-01-01

This study was designed to investigate the effects of local delivery of adipose-derived stem cells (ADSCs) transfected with transcription factor osterix (OSX) on bone formation during distraction osteogenesis. New Zealand white rabbits (n=54) were randomly divided into three groups (18 rabbits per group). A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the right mandib...

Functional polyaniline nanofibre mats for human adipose-derived stem cell proliferation and adhesion

Energy Technology Data Exchange (ETDEWEB)

Abdul Rahman, Norizah, E-mail: norizah@science.putra.edu.my [Polymer Electronics Research Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Department of Chemistry, University of Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan (Malaysia); Feisst, Vaughan [School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Dickinson, Michelle E. [Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Malmström, Jenny [Polymer Electronics Research Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Dunbar, P. Rod [School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Maurice Wilkins Centre, Private Bag 92019, Auckland (New Zealand); Travas-Sejdic, Jadranka, E-mail: j.travas-sejdic@auckland.ac.nz [Polymer Electronics Research Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); MacDiarmid Institute for Advanced Materials and Nanotechnology, P.O. Box 600, Wellington 6140 (New Zealand)

2013-02-15

Conductive polymer poly(aniline-co-m-aminobenzoic acid) (P(ANI-co-m-ABA)) and polyaniline (PANI) were blended with a biodegradable, biocompatible polymer, poly(L-lactic acid) and were electrospun into nanofibres to investigate their potential application as a scaffold for human adipose-derived stem cells (hASCs). These polymers, in both conductive and non-conductive form, were electrospun with average fibre diameters of less than 400 nm. Novel nanoindentation results obtained on the individual nanofibres revealed that the elastic moduli of the nanofibres are much higher at the surface (4–10 GPa, h{sub max} <75 nm) than in the inner fibre core (2–4 GPa, h{sub max} >75 nm). The composite nanofibres showed great promise as a scaffold for hASCs as they supported the cell adhesion and proliferation. After 1 week of cell culture hASCs were well spread on the substrates with abundant focal adhesions. The electrospun mats provide the cells with comparably stiff, sub-micron sized fibres as anchoring points on a substrate of high porosity. The conductive nature of these composite nanofibres offers exciting opportunities for electrical stimulation of the cells. - Highlights: ► Polyaniline and its copolymer's nanofibres were prepared by electrospinning. ► The elastic modulus of a single polyaniline composite nanofibres were determined. ► Elastic moduli of the nanofibres are much higher at the surface than the inner core. ► The electrospun mats supported the cell adhesion and proliferation. ► The nanofibres show great promise as a scaffold for adipose derived stem cells.

Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.

Directory of Open Access Journals (Sweden)

Thomas A Mendel

Full Text Available Retinal vasculopathies, including diabetic retinopathy (DR, threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy.We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR, ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area. ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction. Treatment of ASCs with transforming growth factor beta (TGF-β1 enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection.ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple murine models of retinal vasculopathy. The pericyte phenotype demonstrated

Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells

NARCIS (Netherlands)

Lu, Z.F.; Zandieh Doulabi, B.; Wuisman, P.I.; Bank, R.A.; Helder, M.N.

2008-01-01

Tissue microenvironment plays a critical role in guiding local stem cell differentiation. Within the intervertebral disc, collagen type II and nucleus pulposus (NP) cells are two major components. This study aimed to investigate how collagen type II and NP cells affect adipose tissue-derived stem

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

Science.gov (United States)

Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

2012-12-17

Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

Generation of Dopamine-Secreting Cells from Human Adipose Tissue-Derived Stem Cells In Vitro.

Science.gov (United States)

Soheilifar, Mohammad Hasan; Javeri, Arash; Amini, Hossein; Taha, Masoumeh Fakhr

2018-03-12

Several studies have demonstrated the differentiation of human adipose tissue-derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the fate of these cells toward dopaminergic neurons has not been frequently reported. The aim of this study was to investigate dopaminergic specification of hADSCs in vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog, fibroblast growth factor 8, basic fibroblast growth factor, and brain-derived neurotrophic factor were used under a low serum condition. As the control group, the ADSCs were cultured under the same low serum condition without the dopaminergic cocktail. At the end of differentiation period, the cells expressed neuron-specific markers, NES, NSE, and NEFL, and dopaminergic markers, EN1, NURR1, PITX3, VMAT2, TH, and GIRK2 genes. TH, NURR1, and EN1 mRNAs were upregulated in the dopaminergic group compared with the control group. NEFL and TH proteins were also expressed in the differentiated cells. A total of 27.9% of the cells differentiated in dopaminergic induction medium showed positive staining for TH protein. Based on reversed-phase high-performance liquid chromatography analysis, the differentiated cells released a significant amount of dopamine in response to KCl-induced depolarization. In conclusion, results of this study indicate that hADSCs can be induced by a growth factor cocktail to produce dopamine secreting cells with possible applications for future cell replacement therapy of Parkinson's disease.

Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study.

Science.gov (United States)

Han, T S; Hart, C L; Haig, C; Logue, J; Upton, M N; Watt, G C M; Lean, M E J

2015-11-02

Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. Cross-sectional general population survey. Scotland. 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45-64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30-59 years surveyed in 1996. Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. Regression coefficients for BMI associations between father-son (0.30) and mother-daughter (0.33) were greater than father-daughter (0.23) or mother-son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (pparental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. There are modest genetic/epigenetic influences on the environmental factors behind adverse adiposity. Maternal smoking appears a specific hazard on obesity and metabolic

Specific profiles of ion channels and ionotropic receptors define adipose- and bone marrow derived stromal cells.

Czech Academy of Sciences Publication Activity Database

Forostyak, Oksana; Butenko, Olena; Anděrová, Miroslava; Forostyak, Serhiy; Syková, Eva; Verkhratsky, A.; Dayanithi, Govindan

2016-01-01

Roč. 16, č. 3 (2016), s. 622-634 ISSN 1873-5061 R&D Projects: GA ČR(CZ) GA14-34077S; GA ČR(CZ) GAP304/11/2373; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : adipose derived stromal cells * bone marrow stromal cell * Ca(2+) signaling * Ion channels Subject RIV: FH - Neurology Impact factor: 3.494, year: 2016

Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival

DEFF Research Database (Denmark)

Kølle, Stig-Frederik Trojahn; Fischer-Nielsen, Anne; Mathiasen, Anders Bruun

2013-01-01

Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival ...... of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts....

Supplementation of fat grafts with adipose-derived regenerative cells in reconstructive surgery [Stammzellangereicherte Fetttransplantation in der rekonstruktiven Chirurgie

Directory of Open Access Journals (Sweden)

Herold, C.

2012-09-01

Full Text Available [english] Introduction: The fraction of regenerative cells in adipose tissue has been described to be even higher than in bone marrow. Adipose tissue itself is excessively available in most patients. Given that adipose tissue is abundant in majority of patients adipose derrived stem cells (ASCs have come under scrutiny for regenerative procedures in reconstructive surgery.Material and methods: ASCs were extracted by the Celution system for enrichment of fat grafts that were administered in patients with decreased wound healing, soft tissue or scar defects.Results: All patients were satisfied after reconstruction with ASCs augmented fat grafts and no side effects were observed. Discussion: The Celution system provides fast recovery of ASCs which can be immediately utilized for appropriate application. Since a high number of stem cells are harvested from fat tissue no expansion of cells is needed as described for bone marrow derived stem cells. Enrichment of fat graft with ASCs is of great interest due to their reported angiogenetic effect. The reported cases demonstrate the potential of ASCs in the field of regenerative medicine and encourage further application in reconstructive surgery.[german] Einleitung: Es konnte gezeigt werden, dass der Anteil regenerativer Zellen im Fettgewebe höher als im Knochenmark ist. Fettgewebe hingegen ist bei den meisten Patienten exzessiv vorhanden. Das legt den Einsatz von ASCs (adipose derived stem cells bei regenerativen Anwendungen in der rekonstruktiven Chirurgie nahe.Material und Methoden: Mit dem Celution System von Cytori Therapeutics Inc. prozessierte, ASC angereicherte Fetttransplantate werden an vier Patienten mit Weichteildefiziten und störenden Narben sowie Wundheilungsstörungen angewendet.Ergebnisse: Insbesondere bei Patienten mit Weichteildefiziten und Narben konnte eine suffiziente Volumenaugmentation und ansprechende Verbesserung der Narben erzielt werden. Es wurden keine Nebenwirkungen

Cell supermarket: Adipose tissue as a source of stem cells

Science.gov (United States)

Adipose tissue is derived from numerous sources, and in recent years has been shown to provide numerous cells from what seemingly was a population of homogeneous adipocytes. Considering the types of cells that adipose tissue-derived cells may form, these cells may be useful in a variety of clinical ...

The role of adipose tissue in cancer-associated cachexia.

Science.gov (United States)

Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

Socio-Demographic and Lifestyle Factors Predict 5-Year Changes in Adiposity among a Group of Black South African Adults

Directory of Open Access Journals (Sweden)

Cornelie Nienaber-Rousseau

2017-09-01

Full Text Available The rising prevalence of obesity and excessive adiposity are global public health concerns. Understanding determinants of changes in adiposity over time is critical for informing effective evidence-based prevention or treatment. However, limited information is available to achieve this objective. Cultural, demographic, environmental, and behavioral factors including socio-economic status (SES likely account for obesity development. To this end, we related these variables to anthropometric measures in 1058 black adult Tswana-speaking South Africans who were HIV negative in a prospective study over five years. Body mass index (BMI and waist circumference increased in both sexes, whereas triceps skinfold thickness remained the same. Over the five years, women moved to higher BMI categories and more were diagnosed with central obesity. Age correlated negatively, whereas SES, physical activity, energy, and fat intake correlated positively with adiposity markers in women. In men, SES, marital status, physical activity, and being urban predicted increases in adiposity. For women, SES and urbanicity increased, whereas menopause and smoking decreased adiposity. Among men, smokers had less change in BMI than those that never smoked over five years. Our findings suggest that interventions, focusing on the urban living, the married and those with the highest SES—the high-risk groups identified herein—are of primary importance to contain morbidity and premature mortality due to obesity in black South Africans.

Adipogenic differentiation of laser-printed 3D tissue grafts consisting of human adipose-derived stem cells

International Nuclear Information System (INIS)

Gruene, M; Deiwick, A; Koch, L; Schlie, S; Unger, C; Chichkov, B N; Pflaum, M; Wilhelmi, M; Haverich, A

2011-01-01

Laser-assisted bioprinting (LaBP) allows the realization of computer-generated 3D tissue grafts consisting of cells embedded in a hydrogel environment. In this study, human adipose-derived stem cells (hASCs) were printed in a free-scalable 3D grid pattern by means of LaBP. We demonstrate that neither the proliferation ability nor the differentiation behaviour of the stem cells was affected by the LaBP procedure. Furthermore, the 3D grafts were differentiated down the adipogenic lineage pathway for 10 days. We verify by quantitative assessments of adipogenic markers that the 3D grafts resemble cell lineages present in natural adipose tissue. Additionally, we provide the proof that even pre-differentiated hASCs could be utilized for the generation of 3D tissue grafts. These results indicate that the biofabrication of living grafts resembling their complex native origin is within reach.

Adipogenic differentiation of laser-printed 3D tissue grafts consisting of human adipose-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Gruene, M; Deiwick, A; Koch, L; Schlie, S; Unger, C; Chichkov, B N [Nanotechnology Department, Laser Zentrum Hannover e.V., Hollerithallee 8, 30419 Hannover (Germany); Pflaum, M; Wilhelmi, M; Haverich, A, E-mail: m.gruene@lzh.de [Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover (Germany)

2011-03-15

Laser-assisted bioprinting (LaBP) allows the realization of computer-generated 3D tissue grafts consisting of cells embedded in a hydrogel environment. In this study, human adipose-derived stem cells (hASCs) were printed in a free-scalable 3D grid pattern by means of LaBP. We demonstrate that neither the proliferation ability nor the differentiation behaviour of the stem cells was affected by the LaBP procedure. Furthermore, the 3D grafts were differentiated down the adipogenic lineage pathway for 10 days. We verify by quantitative assessments of adipogenic markers that the 3D grafts resemble cell lineages present in natural adipose tissue. Additionally, we provide the proof that even pre-differentiated hASCs could be utilized for the generation of 3D tissue grafts. These results indicate that the biofabrication of living grafts resembling their complex native origin is within reach.

The role of undifferentiated adipose-derived stem cells in peripheral nerve repair.

Science.gov (United States)

Zhang, Rui; Rosen, Joseph M

2018-05-01

Peripheral nerve injuries impose significant health and economic consequences, yet no surgical repair can deliver a complete recovery of sensory or motor function. Traditional methods of repair are less than ideal: direct coaptation can only be performed when tension-free repair is possible, and transplantation of nerve autograft can cause donor-site morbidity and neuroma formation. Cell-based therapy delivered via nerve conduits has thus been explored as an alternative method of nerve repair in recent years. Stem cells are promising sources of the regenerative core material in a nerve conduit because stem cells are multipotent in function, abundant in supply, and more accessible than the myelinating Schwann cells. Among different types of stem cells, undifferentiated adipose-derived stem cell (uASC), which can be processed from adipose tissue in less than two hours, is a promising yet underexplored cell type. Studies of uASC have emerged in the past decade and have shown that autologous uASCs are non-immunogenic, easy to access, abundant in supply, and efficacious at promoting nerve regeneration. Two theories have been proposed as the primary regenerative mechanisms of uASC: in situ trans-differentiation towards Schwann cells, and secretion of trophic and anti-inflammatory factors. Future studies need to fully elucidate the mechanisms, side effects, and efficacy of uASC-based nerve regeneration so that uASCs can be utilized in clinical settings.

Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Fiedler, Tomas; Salamon, Achim; Adam, Stefanie; Herzmann, Nicole; Taubenheim, Jan; Peters, Kirsten

2013-01-01

Adult mesenchymal stem cells (MSC) are present in several tissues, e.g. bone marrow, heart muscle, brain and subcutaneous adipose tissue. In invasive infections MSC get in contact with bacteria and bacterial components. Not much is known about how bacterial pathogens interact with MSC and how contact to bacteria influences MSC viability and differentiation potential. In this study we investigated the impact of three different wound infection relevant bacteria, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes, and the cell wall components lipopolysaccharide (LPS; Gram-negative bacteria) and lipoteichoic acid (LTA; Gram-positive bacteria) on viability, proliferation, and osteogenic as well as adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (adMSC). We show that all three tested species were able to attach to and internalize into adMSC. The heat-inactivated Gram-negative E. coli as well as LPS were able to induce proliferation and osteogenic differentiation but reduce adipogenic differentiation of adMSC. Conspicuously, the heat-inactivated Gram-positive species showed the same effects on proliferation and adipogenic differentiation, while its cell wall component LTA exhibited no significant impact on adMSC. Therefore, our data demonstrate that osteogenic and adipogenic differentiation of adMSC is influenced in an oppositional fashion by bacterial antigens and that MSC-governed regeneration is not necessarily reduced under infectious conditions. - Highlights: • Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli bind to and internalize into adMSC. • Heat-inactivated cells of these bacterial species trigger proliferation of adMSC. • Heat-inactivated E. coli and LPS induce osteogenic differentiation of adMSC. • Heat-inactivated E. coli and LPS reduce adipogenic differentiation of adMSC. • LTA does not influence adipogenic or osteogenic differentiation of adMSC

Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Fiedler, Tomas, E-mail: tomas.fiedler@med.uni-rostock.de [Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock (Germany); Salamon, Achim; Adam, Stefanie; Herzmann, Nicole [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Taubenheim, Jan [Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock (Germany); Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Peters, Kirsten [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

2013-11-01

Adult mesenchymal stem cells (MSC) are present in several tissues, e.g. bone marrow, heart muscle, brain and subcutaneous adipose tissue. In invasive infections MSC get in contact with bacteria and bacterial components. Not much is known about how bacterial pathogens interact with MSC and how contact to bacteria influences MSC viability and differentiation potential. In this study we investigated the impact of three different wound infection relevant bacteria, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes, and the cell wall components lipopolysaccharide (LPS; Gram-negative bacteria) and lipoteichoic acid (LTA; Gram-positive bacteria) on viability, proliferation, and osteogenic as well as adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (adMSC). We show that all three tested species were able to attach to and internalize into adMSC. The heat-inactivated Gram-negative E. coli as well as LPS were able to induce proliferation and osteogenic differentiation but reduce adipogenic differentiation of adMSC. Conspicuously, the heat-inactivated Gram-positive species showed the same effects on proliferation and adipogenic differentiation, while its cell wall component LTA exhibited no significant impact on adMSC. Therefore, our data demonstrate that osteogenic and adipogenic differentiation of adMSC is influenced in an oppositional fashion by bacterial antigens and that MSC-governed regeneration is not necessarily reduced under infectious conditions. - Highlights: • Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli bind to and internalize into adMSC. • Heat-inactivated cells of these bacterial species trigger proliferation of adMSC. • Heat-inactivated E. coli and LPS induce osteogenic differentiation of adMSC. • Heat-inactivated E. coli and LPS reduce adipogenic differentiation of adMSC. • LTA does not influence adipogenic or osteogenic differentiation of adMSC.

Effects of hypergravity on adipose-derived stem cell morphology, mechanical property and proliferation

Energy Technology Data Exchange (ETDEWEB)

Tavakolinejad, Alireza [Medical Nanotechnology and Tissue Engineering Research Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Rabbani, Mohsen, E-mail: m.rabbani@eng.ui.ac.ir [Department of Biomedical Engineering, University of Isfahan, Isfahan (Iran, Islamic Republic of); Janmaleki, Mohsen [Medical Nanotechnology and Tissue Engineering Research Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2015-08-21

Alteration in specific inertial conditions can lead to changes in morphology, proliferation, mechanical properties and cytoskeleton of cells. In this report, the effects of hypergravity on morphology of Adipose-Derived Stem Cells (ADSCs) are indicated. ADSCs were repeatedly exposed to discontinuous hypergravity conditions of 10 g, 20 g, 40 g and 60 g by utilizing centrifuge (three times of 20 min exposure, with an interval of 40 min at 1 g). Cell morphology in terms of length, width and cell elongation index and cytoskeleton of actin filaments and microtubules were analyzed by image processing. Consistent changes observed in cell elongation index as morphological change. Moreover, cell proliferation was assessed and mechanical properties of cells in case of elastic modulus of cells were evaluated by Atomic Force Microscopy. Increase in proliferation and decrease in elastic modulus of cells are further results of this study. Staining ADSC was done to show changes in cytoskeleton of the cells associated to hypergravity condition specifically in microfilament and microtubule components. After exposing to hypergravity, significant changes were observed in microfilaments and microtubule density as components of cytoskeleton. It was concluded that there could be a relationship between changes in morphology and MFs as the main component of the cells. - Highlights: • Hypergravity (10 g, 20 g, 40 g and 60 g) affects on adipose derived stem cells (ADSCs). • ADSCs after exposure to the hypergravity are more slender. • The height of ADSCs increases in all test groups comparing their control group. • Hypergravity decreases ADSCs modulus of elasticity and cell actin fiber content. • Hypergravity enhances proliferation rate of ADSCs.

Effects of hypergravity on adipose-derived stem cell morphology, mechanical property and proliferation

International Nuclear Information System (INIS)

Tavakolinejad, Alireza; Rabbani, Mohsen; Janmaleki, Mohsen

2015-01-01

Alteration in specific inertial conditions can lead to changes in morphology, proliferation, mechanical properties and cytoskeleton of cells. In this report, the effects of hypergravity on morphology of Adipose-Derived Stem Cells (ADSCs) are indicated. ADSCs were repeatedly exposed to discontinuous hypergravity conditions of 10 g, 20 g, 40 g and 60 g by utilizing centrifuge (three times of 20 min exposure, with an interval of 40 min at 1 g). Cell morphology in terms of length, width and cell elongation index and cytoskeleton of actin filaments and microtubules were analyzed by image processing. Consistent changes observed in cell elongation index as morphological change. Moreover, cell proliferation was assessed and mechanical properties of cells in case of elastic modulus of cells were evaluated by Atomic Force Microscopy. Increase in proliferation and decrease in elastic modulus of cells are further results of this study. Staining ADSC was done to show changes in cytoskeleton of the cells associated to hypergravity condition specifically in microfilament and microtubule components. After exposing to hypergravity, significant changes were observed in microfilaments and microtubule density as components of cytoskeleton. It was concluded that there could be a relationship between changes in morphology and MFs as the main component of the cells. - Highlights: • Hypergravity (10 g, 20 g, 40 g and 60 g) affects on adipose derived stem cells (ADSCs). • ADSCs after exposure to the hypergravity are more slender. • The height of ADSCs increases in all test groups comparing their control group. • Hypergravity decreases ADSCs modulus of elasticity and cell actin fiber content. • Hypergravity enhances proliferation rate of ADSCs

Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

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Ingrid R. Cordeiro

2015-09-01

Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

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Jaewoo Pak

2016-08-01

Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

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Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

Polymeric film of 6-arm-poly(ethylene glycol) amine graphene oxide with poly (ε-caprolactone): Adherence and growth of adipose derived mesenchymal stromal cells culture on rat bladder

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Durán, Marcela; Durán, Nelson; Luzo, Angela C. M.; Duarte, Adriana S. S.; Volpe, Bruno B.; Ceragioli, Helder J.; Andrade, Patricia F.; De Souza, Joel G.; Fávaro, Wagner J.

2017-06-01

Nanotechnology has been more present in different fields related to health. The need to find a durable material, of easy use, and which does not interfere significantly in the growth and differentiation of stem cells for the construction of a scaffold for use in urologic surgery, with the purpose of reducing infections, regeneration times and even graft rejection during reconstitution in patients with urethral stricture was conducted a broad survey of information about this and came to the consensus of this project: using graphene oxide, a widely studied nanomaterials which has been presenting numerous beneficial results when in contact with the adipose-derived stem cells. Advanced techniques for the growth, differentiation and proliferation of adipose-derived stem cells were used, as well as the characterization of graphene oxide sheets. For this study, it was prepared the graphene oxide/6 ARM-Poly (ethylene glycol) amine films with poly (ε-caprolactone). The graphene suspension in organic solvent was prepared by using an ultrasonicator bath and subsequently, the film was formed by solvent evaporation. Total characterization of graphene oxide/6 ARM-PEG-amine/ poly (ε-caprolactone) film was carried out. It was tested growth and adhesion of adipose-derived stem cells on the film, as well as, were verified the histopathological effects of this scaffold when implanted in the urinary bladder to repair the lesion. Our results demonstrated that this scaffold with adipose-derived stem cells enhanced the repair in rat urinary bladder defect model, resulting in a regular bladder. Improved organized muscle bundles and urothelial layer were observed in animals treated with this scaffold with adipose-derived stem cells compared with those treated only suture thread or scaffold. Thus, our biomaterial could be suitable for tissue engineered urinary tract reconstruction.

Polymeric film of 6-arm-poly(ethylene glycol) amine graphene oxide with poly (ε-caprolactone): Adherence and growth of adipose derived mesenchymal stromal cells culture on rat bladder

International Nuclear Information System (INIS)

Durán, Marcela; Durán, Nelson; Fávaro, Wagner J.; Luzo, Angela C.M.; Duarte, Adriana S. S.; Volpe, Bruno B.; Ceragioli, Helder J.; Andrade, Patricia F.; De Souza, Joel G.

2017-01-01

Nanotechnology has been more present in different fields related to health. The need to find a durable material, of easy use, and which does not interfere significantly in the growth and differentiation of stem cells for the construction of a scaffold for use in urologic surgery, with the purpose of reducing infections, regeneration times and even graft rejection during reconstitution in patients with urethral stricture was conducted a broad survey of information about this and came to the consensus of this project: using graphene oxide, a widely studied nanomaterials which has been presenting numerous beneficial results when in contact with the adipose-derived stem cells. Advanced techniques for the growth, differentiation and proliferation of adipose-derived stem cells were used, as well as the characterization of graphene oxide sheets. For this study, it was prepared the graphene oxide/6 ARM-Poly (ethylene glycol) amine films with poly (ε-caprolactone). The graphene suspension in organic solvent was prepared by using an ultrasonicator bath and subsequently, the film was formed by solvent evaporation. Total characterization of graphene oxide/6 ARM-PEG-amine/ poly (ε-caprolactone) film was carried out. It was tested growth and adhesion of adipose-derived stem cells on the film, as well as, were verified the histopathological effects of this scaffold when implanted in the urinary bladder to repair the lesion. Our results demonstrated that this scaffold with adipose-derived stem cells enhanced the repair in rat urinary bladder defect model, resulting in a regular bladder. Improved organized muscle bundles and urothelial layer were observed in animals treated with this scaffold with adipose-derived stem cells compared with those treated only suture thread or scaffold. Thus, our biomaterial could be suitable for tissue engineered urinary tract reconstruction. (paper)

The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy.

Science.gov (United States)

Kilinc, Mehmet Okyay; Santidrian, Antonio; Minev, Ivelina; Toth, Robert; Draganov, Dobrin; Nguyen, Duong; Lander, Elliot; Berman, Mark; Minev, Boris; Szalay, Aladar A

2018-02-07

Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer. Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34 high CD45 - CD31 - CD146 - adipose-derived stromal/stem cells (ADSCs), CD34 low CD45 + CD206 + CD31 - CD146 - hematopoietic stem cell-progenitors (HSC-progenitors), CD34 high CD45 - CD31 + CD146 + adipose tissue-endothelial cells and CD45 - CD34 - CD31 - CD146 + pericytes. Culturing and expanding of SVF revealed a homogenous population lacking hematopoietic lineage markers CD45 and CD34, but were positive for CD90, CD73, CD105, and CD44. Flow cytometry sorting of viable individual subpopulations revealed that ADSCs had the capacity to grow in adherent culture. The identity of the expanded cells as mesenchymal stem cells (MSCs) was further confirmed based on their differentiation into adipogenic and osteogenic lineages. To identify the potential factors, which may determine the beneficial outcome of treatment, we followed 44 patients post-SVF treatment. The gender, age, clinical condition, certain SVF-dose and route of injection, did not play a role on the clinical outcome. Interestingly, SVF yield seemed to be affected by patient's characteristic to various extents. Furthermore, the therapy with adipose-derived and expanded-mesenchymal stem cells (ADE-MSCs) on a limited number of patients, did not suggest increased efficacies compared to SVF treatment. Therefore, we tested the hypothesis that a certain combination

Proliferation of Keratinocytes Induced by Adipose-Derived Stem Cells on a Chitosan Scaffold and Its Role in Wound Healing, a Review

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Sankaralakshmi Gomathysankar

2014-09-01

Full Text Available In the field of tissue engineering and reconstruction, the development of efficient biomaterial is in high demand to achieve uncomplicated wound healing. Chronic wounds and excessive scarring are the major complications of tissue repair and, as this inadequate healing continues to increase, novel therapies and treatments for dysfunctional skin repair and reconstruction are important. This paper reviews the various aspects of the complications related to wound healing and focuses on chitosan because of its unique function in accelerating wound healing. The proliferation of keratinocytes is essential for wound closure, and adipose-derived stem cells play a significant role in wound healing. Thus, chitosan in combination with keratinocytes and adipose-derived stem cells may act as a vehicle for delivering cells, which would increase the proliferation of keratinocytes and help complete recovery from injuries.

Early adiposity rebound: causes and consequences for obesity in children and adults.

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Rolland-Cachera, M F; Deheeger, M; Maillot, M; Bellisle, F

2006-12-01

Childhood obesity is an important public health problem, with a rapidly increasing frequency worldwide. Identification of critical periods for the development of childhood and adolescent obesity could be very useful for targeting prevention measures. Weight status in early childhood is a poor predictor of adult adiposity status, and most obese adults were not obese as children. We first proposed to use the body mass index (BMI) charts to monitor individual BMI development. The adiposity rebound (AR) corresponds to the second rise in BMI curve that occurs between ages 5 and 7 years. It is not as direct a measure as BMI at any age, but because it involves the examination of several points during growth, and because it is identified at a time when adiposity level clearly change directions, this method provides information that can help us understand individual changes and the development of health risks. An early AR is associated with an increased risk of overweight. It is inversely associated with bone age, and reflects accelerated growth. The early AR recorded in most obese subjects and the striking difference in the mean age at AR between obese subjects (3 years) and non-obese subjects (6 years) suggest that factors have operated very early in life. The typical pattern associated with an early AR is a low BMI followed by increased BMI level after the rebound. This pattern is recorded in children of recent generations as compared to those of previous generations. This is owing to the trend of a steeper increase of height as compared to weight in the first years of life. This typical BMI pattern (low, followed by high body fatness level) is associated with metabolic diseases such as diabetes and coronary heart diseases. Low body fatness before the AR suggests that an energy deficit had occurred at an early stage of growth. It can be attributable to the high-protein, low-fat diet fed to infants at a time of high energy needs, the former triggering height velocity and

Adipose-Derived Stem Cells Respond to Increased Osmolarities.

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Urška Potočar

Full Text Available Cell therapies present a feasible option for the treatment of degenerated cartilaginous and intervertebral disc (IVD tissues. Microenvironments of these tissues are specific and often differ from the microenvironment of cells that, could be potentially used for therapy, e.g. human adipose-derived stem cells (hASC. To ensure safe and efficient implantation of hASC, it is important to evaluate how microenvironmental conditions at the site of implantation affect the implanted cells. This study has demonstrated that cartilaginous tissue-specific osmolarities ranging from 400-600 mOsm/L affected hASC in a dose- and time-dependent fashion in comparison to 300 mOsm/L. Increased osmolarities resulted in transient (nuclear DNA and actin reorganisation and non-transient, long-term morphological changes (vesicle formation, increase in cell area, and culture morphology, as well as reduced proliferation in monolayer cultures. Increased osmolarities diminished acid proteoglycan production and compactness of chondrogenically induced pellet cultures, indicating decreased chondrogenic potential. Viability of hASC was strongly dependent on the type of culture, with hASC in monolayer culture being more tolerant to increased osmolarity compared to hASC in suspension, alginate-agarose hydrogel, and pellet cultures, thus emphasizing the importance of choosing relevant in vitro conditions according to the specifics of clinical application.

Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

NARCIS (Netherlands)

Naaijkens, B.A.; Niessen, H.W.M.; Prins, H.J.; Krijnen, P.A.J.; Kokhuis, T.J.A.; de Jong, N.; van Hinsbergh, V.W.M.; Kamp, O.; Helder, M.N.; Musters, R.J.P.; van Dijk, A.; Juffermans, L.J.M.

2012-01-01

Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically,

Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

DEFF Research Database (Denmark)

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

2011-01-01

Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

NARCIS (Netherlands)

B. Naaijkens (Benno); H.W.M. Niessen (Hans ); H.-J. Prins (H.); P.A.J. Krijnen (Paul); T.J.A. Kokhuis (Tom); N. de Jong (Nico); V.W.M. van Hinsbergh (Victor); O. Kamp (Otto); K. Helder MScN (Onno); R.J.P. Musters (René); A. van Dijk (Annemieke); L.J.M. Juffermans (Lynda)

2012-01-01

textabstractAdipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically,

Side-by-Side Comparison of the Biological Characteristics of Human Umbilical Cord and Adipose Tissue-Derived Mesenchymal Stem Cells

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Li Hu

2013-01-01

Full Text Available Both human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs have been explored as attractive mesenchymal stem cells (MSCs sources, but very few parallel comparative studies of these two cell types have been made. We designed a side-by-side comparative study by isolating MSCs from the adipose tissue and umbilical cords from mothers delivering full-term babies and thus compared the various biological aspects of ASCs and UC-MSCs derived from the same individual, in one study. Both types of cells expressed cell surface markers characteristic of MSCs. ASCs and UC-MSCs both could be efficiently induced into adipocytes, osteoblasts, and neuronal phenotypes. While there were no significant differences in their osteogenic differentiation, the adipogenesis of ASCs was more prominent and efficient than UC-MSCs. In the meanwhile, ASCs responded better to neuronal induction methods, exhibiting the higher differentiation rate in a relatively shorter time. In addition, UC-MSCs exhibited a more prominent secretion profile of cytokines than ASCs. These results indicate that although ASCs and UC-MSCs share considerable similarities in their immunological phenotype and pluripotentiality, certain biological differences do exist, which might have different implications for future cell-based therapy.

Bone marrow-derived stromal cells are more beneficial cell sources for tooth regeneration compared with adipose-derived stromal cells.

Science.gov (United States)

Ye, Lanfeng; Chen, Lin; Feng, Fan; Cui, Junhui; Li, Kaide; Li, Zhiyong; Liu, Lei

2015-10-01

Tooth loss is presently a global epidemic and tooth regeneration is thought to be a feasible and ideal treatment approach. Choice of cell source is a primary concern in tooth regeneration. In this study, the odontogenic differentiation potential of two non-dental-derived stem cells, adipose-derived stromal cells (ADSCs) and bone marrow-derived stromal cells (BMSCs), were evaluated both in vitro and in vivo. ADSCs and BMSCs were induced in vitro in the presence of tooth germ cell-conditioned medium (TGC-CM) prior to implantation into the omentum majus of rats, in combination with inactivated dentin matrix (IDM). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of odontogenic-related genes. Immunofluorescence and immunohistochemical assays were used to detect the protein levels of odontogenic-specific genes, such as DSP and DMP-1 both in vitro and in vivo. The results suggest that both ADSCs and BMSCs have odontogenic differentiation potential. However, the odontogenic potential of BMSCs was greater compared with ADSCs, showing that BMSCs are a more appropriate cell source for tooth regeneration. © 2015 International Federation for Cell Biology.

Does youth adiposity, or change in adiposity from youth to adulthood, predict metabolically healthy obesity in adulthood?

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Smith, K J; Bessell, E; Magnussen, C G; Dwyer, T; Venn, A J

2016-10-01

Individuals with metabolically healthy obesity (MHO) do not have the metabolic complications usually associated with obesity. To examine whether youth adiposity, or change in adiposity from youth to adulthood, predicts MHO 20 years later. A national sample of 2410 Australian participants had height, weight and waist circumference (WC) measured in 1985 (7-15 years old) and 2004-2006 (26-36 years old). A fasting blood sample was taken in 2004-2006. MHO was defined as body mass index (BMI) ≥30 kg m(-2) , normal fasting glucose (1.036 mmol L(-1) men, > 1.295 mmol L(-1) women), blood pressure (youth BMI (or WC) z-score or change in BMI (or WC) z-score from youth to adulthood, adjusted for sex and youth age. In total 323 individuals were obese at follow-up, 79 (24.5%) were MHO. Adult MHO was not associated with youth BMI (RR: 1.00, 95%CI: 0.85-1.19) or WC (RR: 0.93, 95%CI: 0.79-1.11). Individuals were less likely to be MHO if they had larger increases in BMI (BMI RR: 0.74, 95%CI: 0.57-0.97) or WC (RR: 0.70, 95%CI: 0.55-0.90) from youth to adulthood. Change in adiposity from youth to adulthood predicted adult MHO better than youth adiposity alone. © 2015 World Obesity.

Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome.

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Wilfredo Oliva-Olivera

Full Text Available Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs from normal-weight subjects (Nw and obese patients with metabolic syndrome (MS and without metabolic syndrome (NonMS.This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated.Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox-visASC-conditioned culture medium

Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome

Science.gov (United States)

Moreno-Indias, Isabel; Coín-Aragüez, Leticia; Lhamyani, Said; Alcaide Torres, Juan; Fernández-Veledo, Sonia; Vendrell, Joan; Camargo, Antonio; El Bekay, Rajaa; Tinahones, Francisco José

2017-01-01

Background/Objectives Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS). Methods This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated. Results Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox

Potential of Osteoblastic Cells Derived from Bone Marrow and Adipose Tissue Associated with a Polymer/Ceramic Composite to Repair Bone Tissue.

Science.gov (United States)

Freitas, Gileade P; Lopes, Helena B; Almeida, Adriana L G; Abuna, Rodrigo P F; Gimenes, Rossano; Souza, Lucas E B; Covas, Dimas T; Beloti, Marcio M; Rosa, Adalberto L

2017-09-01

One of the tissue engineering strategies to promote bone regeneration is the association of cells and biomaterials. In this context, the aim of this study was to evaluate if cell source, either from bone marrow or adipose tissue, affects bone repair induced by osteoblastic cells associated with a membrane of poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT). Mesenchymal stem cells (MSC) were isolated from rat bone marrow and adipose tissue and characterized by detection of several surface markers. Also, both cell populations were cultured under osteogenic conditions and it was observed that MSC from bone marrow were more osteogenic than MSC from adipose tissue. The bone repair was evaluated in rat calvarial defects implanted with PVDF-TrFE/BT membrane and locally injected with (1) osteoblastic cells differentiated from MSC from bone marrow, (2) osteoblastic cells differentiated from MSC from adipose tissue or (3) phosphate-buffered saline. Luciferase-expressing osteoblastic cells derived from bone marrow and adipose tissue were detected in bone defects after cell injection during 25 days without difference in luciferin signal between cells from both sources. Corroborating the in vitro findings, osteoblastic cells from bone marrow combined with the PVDF-TrFE/BT membrane increased the bone formation, whereas osteoblastic cells from adipose tissue did not enhance the bone repair induced by the membrane itself. Based on these findings, it is possible to conclude that, by combining a membrane with cells in this rat model, cell source matters and that bone marrow could be a more suitable source of cells for therapies to engineer bone.

Neutron organ dose and the influence of adipose tissue

Science.gov (United States)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

From bench to bedside: use of human adipose-derived stem cells

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Feisst V

2015-11-01

Full Text Available Vaughan Feisst,1 Sarah Meidinger,1 Michelle B Locke2 1Dunbar Laboratory, School of Biological Sciences, 2Department of Surgery, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand Abstract: Since the discovery of adipose-derived stem cells (ASC in human adipose tissue nearly 15 years ago, significant advances have been made in progressing this promising cell therapy tool from the laboratory bench to bedside usage. Standardization of nomenclature around the different cell types used is finally being adopted, which facilitates comparison of results between research groups. In vitro studies have assessed the ability of ASC to undergo mesenchymal differentiation as well as differentiation along alternate lineages (transdifferentiation. Recently, focus has shifted to the immune modulatory and paracrine effects of transplanted ASC, with growing interest in the ASC secretome as a source of clinical effect. Bedside use of ASC is advancing alongside basic research. An increasing number of safety-focused Phase I and Phase IIb trials have been published without identifying any significant risks or adverse events in the short term. Phase III trials to assess efficacy are currently underway. In many countries, regulatory frameworks are being developed to monitor their use and assure their safety. As many trials rely on ASC injected at a distant site from the area of clinical need, strategies to improve the homing and efficacy of transplanted cells are also being explored. This review highlights each of these aspects of the bench-to-bedside use of ASC and summarizes their clinical utility across a variety of medical specialties. Keywords: standardization, bystander effect, stromal cells, mesenchymal stem cells, stromal vascular fraction

Aerobic Exercise Attenuates the Loss of Skeletal Muscle during Energy Restriction in Adults with Visceral Adiposity

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Eiichi Yoshimura

2014-01-01

Full Text Available Objective: To evaluate the effects of energy restriction with or without aerobic exercise on thigh muscle mass and quality in adults with visceral adiposity. Methods: 75 males and females were randomly assigned to the groups ‘diet only' (DO; n = 42 or ‘diet plus aerobic exercise' (D/Ex; n = 33 for 12 weeks. The target energy intake in both groups was 25 kcal/kg of ideal body weight. Subjects in the D/Ex group were instructed to exercise for ≥300 min/week at lactate threshold. Computed tomography was used to measure thigh muscle cross-sectional area (CSA, normal-density muscle area (NDMA, and visceral fat area. Results: Total body weight (DO: -6.6 ± 3.6%; D/Ex: -7.3 ± 4.6% and visceral fat (DO: -16.0 ± 13.8%; D/Ex: -23.1 ± 14.7% decreased significantly in both groups; however, the changes were not significantly different between the two groups. The decrease in muscle CSA was significantly greater in the DO group (-5.1 ± 4.5% compared with the D/Ex group (-2.5 ± 5.0%. NDMA decreased significantly in the DO (-4.9 ± 4.9% but not in the D/Ex group (-1.4 ± 5.0%. Conclusion: Aerobic exercise attenuated the loss of skeletal muscle during energy restriction in adults with visceral adiposity.

Aerobic Exercise Attenuates the Loss of Skeletal Muscle during Energy Restriction in Adults with Visceral Adiposity

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Yoshimura, Eiichi; Kumahara, Hideaki; Tobina, Takuro; Matsuda, Takuro; Watabe, Kiwa; Matono, Sakiko; Ayabe, Makoto; Kiyonaga, Akira; Anzai, Keizo; Higaki, Yasuki; Tanaka, Hiroaki

2014-01-01

Objective To evaluate the effects of energy restriction with or without aerobic exercise on thigh muscle mass and quality in adults with visceral adiposity. Methods 75 males and females were randomly assigned to the groups ‘diet only’ (DO; n = 42) or ‘diet plus aerobic exercise’ (D/Ex; n = 33) for 12 weeks. The target energy intake in both groups was 25 kcal/kg of ideal body weight. Subjects in the D/Ex group were instructed to exercise for ≥300 min/week at lactate threshold. Computed tomography was used to measure thigh muscle cross-sectional area (CSA), normal-density muscle area (NDMA), and visceral fat area. Results Total body weight (DO: −6.6 ± 3.6%; D/Ex: −7.3 ± 4.6%) and visceral fat (DO: −16.0 ± 13.8%; D/Ex: −23.1 ± 14.7%) decreased significantly in both groups; however, the changes were not significantly different between the two groups. The decrease in muscle CSA was significantly greater in the DO group (-5.1 ± 4.5%) compared with the D/Ex group (-2.5 ± 5.0%). NDMA decreased significantly in the DO (-4.9 ± 4.9%) but not in the D/Ex group (-1.4 ± 5.0%). Conclusion Aerobic exercise attenuated the loss of skeletal muscle during energy restriction in adults with visceral adiposity. PMID:24457527

Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

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Siviero-Miachon, Adriana Aparecida; Spinola-Castro, Angela Maria; Lee, Maria Lúcia de Martino; Andreoni, Solange; Geloneze, Bruno; Lederman, Henrique; Guerra-Junior, Gil

2013-01-01

Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process

Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study

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Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten

2017-01-01

The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease...... and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry...... developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials. Stem Cells Translational Medicine 2017;6:1963-1971....

Long Distance Metabolic Regulation through Adipose-Derived Circulating Exosomal miRNAs: A Trail for RNA-Based Therapies?

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Farah Fatima

2017-08-01

Full Text Available The contribution of non-coding RNAs, such as microRNAs (miRNAs in regulating physiological and pathological states has been intensively elucidated during last 15 years. The discovery of circulating miRNAs (cir-miRNAs in variety of body fluids, is, however a recent focus of interest in understanding pathophysiological states of their originating cells/organs. Yet another stimulating debate that takes miRNAs to the next level is their presence in exosomes, and this is truly interesting area of research. Exosomes are cell-derived extracellular vesicles, and are naturally equipped biological vehicles that not only enable functional transfer of miRNAs between cells (horizontal transfer but also foster inter-organ communication, presumably guided by organ specific receptors—decorated on their surface. However, understandings on inter-organ communication elicited by tissue specific exosomal-miRNA fingerprints remain elusive. Recently, Thomou et al., has discovered that adipose tissue contributes a large fraction of adipose specific exosomal-miRNA fingerprints in blood circulation. Experimental evidence emphasize adipose tissue as major depot of cir-miRNAs that sail through blood flow and reach to distal organs—primarily in the liver, where they regulate gene expression of host tissue and elicit metabolic control. This appears to be a genetic form of adipokines (endocrine factors secreted from adipose tissue. We review such offshore metabolic insults, and make an effort to address few important missing links between miRNAs processing and their incorporation into exosomes. We provide potential perspectives on how this knowledge could be steered towards RNA-based therapeutics for monitoring complex metabolic diseases and beyond.

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

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Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

2018-03-01

Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Association between Blood Mercury Level and Visceral Adiposity in Adults

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Jong Suk Park

2017-01-01

Full Text Available BackgroundFew studies have examined the association between mercury exposure and obesity. The aim of this study is to investigate the association between blood mercury concentrations and indices of obesity in adults.MethodsA total of 200 healthy subjects, aged 30 to 64 years, who had no history of cardiovascular or malignant disease, were examined. Anthropometric and various biochemical profiles were measured. Visceral adipose tissue (VAT was measured using dual-energy X-ray absorptiometry (DXA.ResultsAll subjects were divided into three groups according to blood mercury concentrations. Compared with the subjects in the lowest tertile of mercury, those in the highest tertile were more likely to be male; were current alcohol drinkers and smokers; had a higher body mass index (BMI, waist circumference (WC, and VAT; had higher levels of blood pressure, fasting glucose, and insulin resistance; and consumed more fish. The blood mercury concentration was significantly associated with anthropometric parameters, showing relationships with BMI, WC, and VAT. After adjusting for multiple risk factors, the odds ratios (ORs for high mercury concentration was significantly higher in the highest VAT tertile than in the lowest VAT tertile (OR, 2.66; 95% confidence interval, 1.05 to 6.62; P<0.05.ConclusionThe blood mercury concentration was significantly associated with VAT in healthy adults. Further studies are warranted to confirm our findings.

Gold nanoparticles cellular toxicity and recovery: adipose Derived Stromal cells.

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Mironava, Tatsiana; Hadjiargyrou, Michael; Simon, Marcia; Rafailovich, Miriam H

2014-03-01

Gold nanoparticles (AuNPs) are currently used in numerous medical applications. Herein, we describe their in vitro impact on human adipose-derived stromal cells (ADSCs) using 13 nm and 45 nm citrate-coated AuNPs. In their non-differentiated state, ADSCs were penetrated by the AuNPs and stored in vacuoles. The presence of the AuNPs in ADSCs resulted in increased population doubling times, decreased cell motility and cell-mediated collagen contraction. The degree to which the cells were impacted was a function of particle concentration, where the smaller particles required a sevenfold higher concentration to have the same effect as the larger ones. Furthermore, AuNPs reduced adipogenesis as measured by lipid droplet accumulation and adiponectin secretion. These effects correlated with transient increases in DLK1 and with relative reductions in fibronectin. Upon removal of exogenous AuNPs, cellular NP levels decreased and normal ADSC functions were restored. As adiponectin helps regulate energy metabolism, local fluctuations triggered by AuNPs can lead to systemic changes. Hence, careful choice of size, concentration and clinical application duration of AuNPs is warranted.

Adipose derived stem cells in radiotherapy injury: a new frontier

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Lipi eShukla

2015-01-01

Full Text Available Radiotherapy is increasingly used to treat numerous human malignancies. In addition to the beneficial anti-cancer effects, there are a series of undesirable effects on normal host tissues surrounding the target tumour. Whilst the early effects of radiotherapy (desquamation, erythema and hair loss typically resolve, the chronic effects persist as unpredictable and often troublesome sequelae of cancer treatment, long after oncological treatment has been completed. Plastic surgeons are often called upon to treat the problems subsequently arising in irradiated tissues, such as recurrent infection, impaired healing, fibrosis, contracture and/or lymphoedema. Recently, it was anecdotally noted - then validated in more robust animal and human studies - that fat grafting can ameliorate some of these chronic tissue effects. Despite the widespread usage of fat grafting, the mechanism of its action remains poorly understood. This review provides an overview of the current understanding of (i mechanisms of chronic radiation injury and its clinical manifestations; (ii biological properties of fat grafts and their key constituent, Adipose-Derived Stem Cells (ADSCs; (iii the role of ADSCs in radiotherapy-induced soft-tissue injury.

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells.

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Basoli, Valentina; Santaniello, Sara; Cruciani, Sara; Ginesu, Giorgio Carlo; Cossu, Maria Laura; Delitala, Alessandro Palmerio; Serra, Pier Andrea; Ventura, Carlo; Maioli, Margherita

2017-05-05

Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2 , peroxisome proliferator-activated receptor γ ( PPAR-γ ), and that of adipocyte-specific genes, including lipoprotein lipase ( LPL ) and acyl-CoA thioesterase 2 ( ACOT2 ), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.

Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

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Yan Liang

2017-01-01

Full Text Available Adipose tissue-derived stromal cells (ADSCs are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9. Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies.

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Veronesi, Francesca; Maglio, Melania; Tschon, Matilde; Aldini, Nicolò Nicoli; Fini, Milena

2014-07-01

Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose-derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 10(7) cells for heterotopic cartilage formation and 1 × 10(6) cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies. © 2013 Wiley Periodicals, Inc.

Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

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Gayathri Subramanian

2017-01-01

Full Text Available Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds.

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Subramanian, Gayathri; Stasuk, Alexander; Elsaadany, Mostafa; Yildirim-Ayan, Eda

2017-01-01

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

Human Adipose-Derived Mesenchymal Stem/Stromal Cells Handling Protocols. Lipid Droplets and Proteins Double-Staining

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Aldana D. Gojanovich

2018-04-01

Full Text Available Human Adipose-derived mesenchymal stem/stromal cells (hASCs are of great interest because of their potential for therapeutic approaches. The method described here covers every single step necessary for hASCs isolation from subcutaneous abdominal adipose tissue, multicolor phenotyping by flow cytometry, and quantitative determination of adipogenic differentiation status by means of lipid droplets (LDs accumulation, and Western blot analysis. Moreover, to simultaneously analyze both LDs accumulation and cellular proteins localization by fluorescence microscopy, we combined Oil Red O (ORO staining with immunofluorescence detection. For LDs quantification we wrote a program for automatic ORO-stained digital image processing implemented in Octave, a freely available software package. Our method is based on the use of the traditional low cost neutral lipids dye ORO, which can be imaged both by bright-field and fluorescence microscopy. The utilization of ORO instead of other more expensive lipid-specific dyes, together with the fact that the whole method has been designed employing cost-effective culture reagents (standard culture medium and serum, makes it affordable for tight-budget research laboratories. These may be replaced, if necessary or desired, by defined xeno-free reagents for clinical research and applications.

Differential expression pattern of extracellular matrix molecules during chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue

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Mehlhorn, A T; Niemeyer, P; Kaiser, S

2006-01-01

Adipose-derived adult stem cells (ADASCs) or bone marrow-derived mesenchymal stem cells (BMSCs) are considered as alternative cell sources for cell-based cartilage repair due to their ability to produce cartilage-specific matrix. This article addresses the differential expression pattern...... chondroinduction. TGF-beta1 induces alternative splicing of the alpha(1)-procollagen type II transcript in BMSCs, but not in ADASCs. These findings may direct the development of a cell-specific culture environment either to prevent hypertrophy in BMSCs or to promote chondrogenic maturation in ADASCs....

Fibroblast-Derived Extracellular Matrix Induces Chondrogenic Differentiation in Human Adipose-Derived Mesenchymal Stromal/Stem Cells in Vitro

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Kevin Dzobo

2016-08-01

Full Text Available Mesenchymal stromal/stem cells (MSCs represent an area being intensively researched for tissue engineering and regenerative medicine applications. MSCs may provide the opportunity to treat diseases and injuries that currently have limited therapeutic options, as well as enhance present strategies for tissue repair. The cellular environment has a significant role in cellular development and differentiation through cell–matrix interactions. The aim of this study was to investigate the behavior of adipose-derived MSCs (ad-MSCs in the context of a cell-derived matrix so as to model the in vivo physiological microenvironment. The fibroblast-derived extracellular matrix (fd-ECM did not affect ad-MSC morphology, but reduced ad-MSC proliferation. Ad-MSCs cultured on fd-ECM displayed decreased expression of integrins α2 and β1 and subsequently lost their multipotency over time, as shown by the decrease in CD44, Octamer-binding transcription factor 4 (OCT4, SOX2, and NANOG gene expression. The fd-ECM induced chondrogenic differentiation in ad-MSCs compared to control ad-MSCs. Loss of function studies, through the use of siRNA and a mutant Notch1 construct, revealed that ECM-mediated ad-MSCs chondrogenesis requires Notch1 and β-catenin signaling. The fd-ECM also showed anti-senescence effects on ad-MSCs. The fd-ECM is a promising approach for inducing chondrogenesis in ad-MSCs and chondrogenic differentiated ad-MSCs could be used in stem cell therapy procedures.

Adipose stem cells for bone tissue repair

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Ciuffi, Simone; Zonefrati, Roberto; Brandi, Maria Luisa

2017-01-01

Adipose-derived stem/stromal cells (ASCs), together with adipocytes, vascular endothelial cells, and vascular smooth muscle cells, are contained in fat tissue. ASCs, like the human bone marrow stromal/stem cells (BMSCs), can differentiate into several lineages (adipose cells, fibroblast, chondrocytes, osteoblasts, neuronal cells, endothelial cells, myocytes, and cardiomyocytes). They have also been shown to be immunoprivileged, and genetically stable in long-term cultures. Nevertheless, unlik...

The survival condition and immunoregulatory function of adipose stromal vascular fraction (SVF in the early stage of nonvascularized adipose transplantation.

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Ziqing Dong

Full Text Available INTRODUCTION: Adipose tissue transplantation is one of the standard procedures for soft-tissue augmentation, reconstruction, and rejuvenation. However, it is unknown as to how the graft survives after transplantation. We thus seek out to investigate the roles of different cellular components in the survival of graft. MATERIALS & METHODS: The ratios of stromal vascular fraction (SVF cellular components from human adipose tissue were evaluated using flow cytometry. Human liposuction aspirates that were either mixed with marked SVF cells or PBS were transplanted into nude mice. The graft was harvested and stained on days 1,4,7 and 14. The inflammation level of both SVF group and Fat-only group were also evaluated. RESULTS: Flow cytometric analysis showed SVF cells mainly contained blood-derived cells, adipose-derived stromal cells (ASCs, and endothelial cells. Our study revealed that most cells are susceptible to death after transplantation, although CD34+ ASCs can remain viable for 14 days. Notably, we found that ASCs migrated to the peripheral edge of the graft. Moreover, the RT-PCR and the immuno-fluorescence examination revealed that although the SVF did not reduce the number of infiltrating immune cells (macrophages in the transplant, it does have an immunoregulatory function of up-regulating the expression of CD163 and CD206 and down-regulating that of IL-1β, IL-6. CONCLUSIONS: Our study suggests that the survival of adipose tissue after nonvascularized adipose transplantation may be due to the ASCs in SVF cells. Additionally, the immunoregulatory function of SVF cells may be indirectly contributing to the remolding of adipose transplant, which may lead to SVF-enriched adipose transplantation.

Adiposity and psychosocial outcomes at ages 30 and 35.

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McLeod, Geraldine F H; Fergusson, David M; John Horwood, L; Carter, Frances A

2016-02-01

To examine associations between adiposity and adult psychosocial outcomes (depressive symptoms, life satisfaction, self-esteem, household income, personal income, savings/investments) in a New Zealand birth cohort, by gender. Adiposity was assessed using Body Mass Index scores classified on a 3-point scale of BMI: depressive symptoms, life satisfaction, equivalized household income and savings/investments) remaining statistically significant (p < 0.05). In contrast, for males there was a significant (p = 0.008) positive association between adiposity and higher personal net weekly income after covariate adjustment. The findings suggest evidence of gender differences in the associations between adiposity and psychosocial outcomes. For females, there were small but pervasive tendencies for increasing adiposity to be related to more adverse mental health, psychological well-being and economic outcomes; whereas for males adiposity was either unrelated to these outcomes, or in the case of personal income, associated with greater economic advantage. The implications of these findings are discussed.

Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study

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Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten

2017-01-01

and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry......The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease......-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen...

The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

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Abrahamse, Heidi

2009-09-01

Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of blastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and

Effect of labeling with iron oxide particles or nanodiamonds on the functionality of adipose-derived mesenchymal stem cells.

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Sinead P Blaber

Full Text Available Stem cells are increasingly the focus of translational research as well as having emerging roles in human cellular therapy. To support these uses there is a need for improved methods for in vivo cell localization and tracking. In this study, we examined the effects of cell labeling on the in vitro functionality of human adipose-derived mesenchymal stem cells. Our results provide a basis for future in vivo studies investigating implanted cell fate and longevity. In particular, we investigated the effects of two different particles: micron-sized (~0.9 µm fluorescently labeled (Dragon Green superparamagnetic iron oxide particles (M-SPIO particles; and, carboxylated nanodiamonds of ~0.25 µm in size. The effects of labeling on the functionality of adipose-derived MSCs were assessed by in vitro morphology, osteogenic and adipogenic differentiation potential, CD marker expression, cytokine secretion profiling and quantitative proteomics of the intra-cellular proteome. The differentiation and CD marker assays for stem-like functionality were not altered upon label incorporation and no secreted or intra-cellular protein changes indicative of stress or toxicity were detected. These in vitro results indicate that the M-SPIO particles and nanodiamonds investigated in this study are biocompatible with MSCs and therefore would be suitable labels for cell localization and tracking in vivo.

Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation

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Liu, Tao; Zhang, Yue; Shen, Zhongyang; Zou, Xunfeng; Chen, Xiaobo; Chen, Li; Wang, Yuliang

2016-01-01

Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immu...

Effects of fullerol on the osteogenic differentiation of adipose-derived mesenchymal stem cells

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Yan-ting TANG

2016-09-01

Full Text Available Objective 　To investigate the effect of fullerol on the osteogenic differentiation of rat adipose-derived mesenchymal stem cells (rADSCs based on hanging drop culture. Methods 　rADSC spheres were formed by hanging drop culture for 3 days, then the spheres were dissociated to single cell by trypsin (called rADSC sphere-derived cells. The rADSC sphere-derived cells were cultured in 2-D adherent cell cultures for 24 hours, then the ordinary culture medium was replaced by osteogenic induction medium (osteogenic medium, OM. OM without fullerol served as control group (CM; OM with 1.0μmol/L fullerol was used as the experimental group (OM+Ful1.0μmol/L. Two groups were induced to differentiation for 14d and 21d, using two methods of alizarin red staining and quantitative real-time PCR (qPCR to detecte the ability of rADSC sphere-derived cells differentiating into osteoblasts. Results 　rADSCs could form a uniform size microspheres structure through hanging drop culture for 3 days; rADSC sphere-derived cells were obtained by dissipation of trypsin. Compared with OM group, OM+Ful1.0μmol/L can make rADSC sphere-derived cells form more mineralized calcium nodules, and enhance the expression of the relevant osteogenic gene Runx2, OCN and ColI. Conclusion 　Fullerol can significantly enhance the osteogenic differentiation of rADSCs based on hanging drop culture, and it is helpful to improve the efficiency of osteogenic induction of rADSCs. DOI: 10.11855/j.issn.0577-7402.2016.08.03

Neural differentiation of adipose-derived stem cells by indirect co-culture with Schwann cells

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Li Xiaojie

2009-01-01

Full Text Available To investigate whether adipose-derived stem cells (ADSCs could be subject to neural differentiation induced only by Schwann cell (SC factors, we co-cultured ADSCs and SCs in transwell culture dishes. Immunoassaying, Western blot analysis, and RT-PCR were performed (1, 3, 7, 14 d and the co-cultured ADSCs showed gene and protein expression of S-100, Nestin, and GFAP. Further, qRT-PCR disclosed relative quantitative differences in the above three gene expressions. We think ADSCs can undergo induced neural differentiation by being co-cultured with SCs, and such differentia­tions begin 1 day after co-culture, become apparent after 7 days, and thereafter remain stable till the 14th day.

Functional characteristics of mesenchymal stem cells derived from the adipose tissue of a patient with achondroplasia.

Science.gov (United States)

Park, Jeong-Ran; Lee, Hanbyeol; Kim, Chung-Hyo; Hong, Seok-Ho; Ha, Kwon-Soo; Yang, Se-Ran

2016-05-01

Mesenchymal stem cells (MSCs) can be isolated from various tissues including bone marrow, adipose tissue, skin dermis, and umbilical Wharton's jelly as well as injured tissues. MSCs possess the capacity for self-renewal and the potential for differentiation into adipogenic, osteogenic, and chondrogenic lineages. However, the characteristics of MSCs in injured tissues, such as achondroplasia (ACH), are not well known. In this study, we isolated MSCs from human subcutaneous adipose (ACH-SAMSCs) tissue and circumjacent human adipose tissue of the cartilage (ACH-CAMSCs) from a patient with ACH. We then analyzed the characterization of ACH-SAMSCs and ACH-CAMSCs, compared with normal human dermis-derived MSCs (hDMSCs). In flow cytometry analysis, the isolated ACH-MSCs expressed low levels of CD73, CD90, and CD105, compared with hDMSCs. Moreover, both ACH- SAMSCs and ACH-CAMSCs had constitutionally overactive fibroblast growth factor receptor 3 (FGFR3) and exhibited significantly reduced osteogenic differentiation, compared to enhanced adipogenic differentiation. The activity of extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) was increased in ACH-MSCs. In addition, the efficacy of osteogenic differentiation was slightly restored in osteogenic differentiation medium with MAPKs inhibitors. These results suggest that they play essential roles in MSC differentiation toward adipogenesis in ACH pathology. In conclusion, the identification of the characteristics of ACH-MSCs and the favoring of adipogenic differentiation via the FGFR3/MAPK axis might help to elucidate the pathogenic mechanisms relevant to other skeletal diseases and could provide targets for therapeutic interventions.

Efficient myogenic differentiation of human adipose-derived stem cells by the transduction of engineered MyoD protein

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Sung, Min Sun [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of); Mun, Ji-Young [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kwon, Ohsuk [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of); Kwon, Ki-Sun [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Oh, Doo-Byoung, E-mail: dboh@kribb.re.kr [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of)

2013-07-19

Highlights: •MyoD was engineered to contain protein transduction domain and endosome-disruptive INF7 peptide. •The engineered MyoD-IT showed efficient nuclear targeting through an endosomal escape by INF7 peptide. •By applying MyoD-IT, human adipose-derived stem cells (hASCs) were differentiated into myogenic cells. •hASCs differentiated by applying MyoD-IT fused to myotubes through co-culturing with mouse myoblasts. •Myogenic differentiation using MyoD-IT is a safe method without the concern of altering the genome. -- Abstract: Human adipose-derived stem cells (hASCs) have great potential as cell sources for the treatment of muscle disorders. To provide a safe method for the myogenic differentiation of hASCs, we engineered the MyoD protein, a key transcription factor for myogenesis. The engineered MyoD (MyoD-IT) was designed to contain the TAT protein transduction domain for cell penetration and the membrane-disrupting INF7 peptide, which is an improved version of the HA2 peptide derived from influenza. MyoD-IT showed greatly improved nuclear targeting ability through an efficient endosomal escape induced by the pH-sensitive membrane disruption of the INF7 peptide. By applying MyoD-IT to a culture, hASCs were efficiently differentiated into long spindle-shaped myogenic cells expressing myosin heavy chains. Moreover, these cells differentiated by an application of MyoD-IT fused to myotubes with high efficiency through co-culturing with mouse C2C12 myoblasts. Because internalized proteins can be degraded in cells without altering the genome, the myogenic differentiation of hASCs using MyoD-IT would be a safe and clinically applicable method.

Efficient myogenic differentiation of human adipose-derived stem cells by the transduction of engineered MyoD protein

International Nuclear Information System (INIS)

Sung, Min Sun; Mun, Ji-Young; Kwon, Ohsuk; Kwon, Ki-Sun; Oh, Doo-Byoung

2013-01-01

Highlights: •MyoD was engineered to contain protein transduction domain and endosome-disruptive INF7 peptide. •The engineered MyoD-IT showed efficient nuclear targeting through an endosomal escape by INF7 peptide. •By applying MyoD-IT, human adipose-derived stem cells (hASCs) were differentiated into myogenic cells. •hASCs differentiated by applying MyoD-IT fused to myotubes through co-culturing with mouse myoblasts. •Myogenic differentiation using MyoD-IT is a safe method without the concern of altering the genome. -- Abstract: Human adipose-derived stem cells (hASCs) have great potential as cell sources for the treatment of muscle disorders. To provide a safe method for the myogenic differentiation of hASCs, we engineered the MyoD protein, a key transcription factor for myogenesis. The engineered MyoD (MyoD-IT) was designed to contain the TAT protein transduction domain for cell penetration and the membrane-disrupting INF7 peptide, which is an improved version of the HA2 peptide derived from influenza. MyoD-IT showed greatly improved nuclear targeting ability through an efficient endosomal escape induced by the pH-sensitive membrane disruption of the INF7 peptide. By applying MyoD-IT to a culture, hASCs were efficiently differentiated into long spindle-shaped myogenic cells expressing myosin heavy chains. Moreover, these cells differentiated by an application of MyoD-IT fused to myotubes with high efficiency through co-culturing with mouse C2C12 myoblasts. Because internalized proteins can be degraded in cells without altering the genome, the myogenic differentiation of hASCs using MyoD-IT would be a safe and clinically applicable method

One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect: a pilot study

NARCIS (Netherlands)

Jurgens, W.J.F.M.; Kroeze, R.J.; Zandieh-Doulabi, B.; van Dijk, A.; Renders, G.A.P.; Smit, T.H.; van Milligen, F.J.; Ritt, M.J.P.F.

2013-01-01

Regenerative therapies offer attractive alternatives for the treatment of osteochondral defects. Adipose-derived stromal vascular fraction (SVF) cells allow the development of one-step surgical procedures by their abundant availability and high frequency. In this pilot study we evaluated the in vivo

Adipose Tissue Biology: An Update Review

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Anna Meiliana

2009-12-01

Full Text Available BACKGROUND: Obesity is a major health problem in most countries in the world today. It increases the risk of diabetes, heart disease, fatty liver and some form of cancer. Adipose tissue biology is currently one of the “hot” areas of biomedical science, as fundamental for the development of novel therapeutics for obesity and its related disorders.CONTENT: Adipose tissue consist predominantly of adipocytes, adipose-derived stromal cells (ASCs, vascular endothelial cells, pericytes, fibroblast, macrophages, and extracellular matrix. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissue to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. Obesity causes adipose tissue dysfunction and results in obesity-related disorders. SUMMARY: It is now clear that adipose tissue is a complex and highly active metabolic and endocrine organ. Undestanding the molecular mechanisms underlying obesity and its associated disease cluster is also of great significance as the need for new and more effective therapeutic strategies is more urgent than ever.  KEYWORDS: obesity, adipocyte, adipose, tissue, adipogenesis, angiogenesis, lipid droplet, lipolysis, plasticity, dysfunction.

Correlation of adiposity indices with cardiovascular disease risk factors in healthy adults of Singapore: a cross-sectional study.

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Bi, Xinyan; Tey, Siew Ling; Leong, Claudia; Quek, Rina; Loo, Yi Ting; Henry, Christiani Jeyakumar

2016-01-01

healthy Asian adults. While measures of central adiposity (WC and WHR) tend to show stronger associations with CVD risk factors in males, measures of general adiposity (BAI) seems to be the best predictor in females. The gender differences in the association between adiposity indices and CVD risk factors may relate to different body fat distribution in males and females living in Singapore. These results may find further clinical utility to identify patients with CVD risk factors in a more efficient way.

Injectable biomaterials for adipose tissue engineering

International Nuclear Information System (INIS)

Young, D A; Christman, K L

2012-01-01

Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers but also promote in vivo adipogenesis is beginning to be realized. This paper will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. (paper)

Adenovirus 36 DNA in human adipose tissue.

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Ponterio, E; Cangemi, R; Mariani, S; Casella, G; De Cesare, A; Trovato, F M; Garozzo, A; Gnessi, L

2015-12-01

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro.

Science.gov (United States)

Iser, Isabele C; Ceschini, Stefanie M; Onzi, Giovana R; Bertoni, Ana Paula S; Lenz, Guido; Wink, Márcia R

2016-12-01

Mesenchymal stem cells (MSCs) have recently been described to home to brain tumors and to integrate into the tumor-associated stroma. Understanding the communication between cancer cells and MSCs has become fundamental to determine whether MSC-tumor interactions should be exploited as a vehicle for therapeutic agents or considered a target for intervention. Therefore, we investigated whether conditioned medium from adipose-derived stem cells (ADSCs-CM) modulate glioma tumor cells by analyzing several cell biology processes in vitro. C6 rat glioma cells were treated with ADSCs-CM, and cell proliferation, cell cycle, cell viability, cell morphology, adhesion, migration, and expression of epithelial-mesenchymal transition (EMT)-related surface markers were analyzed. ADSCs-CM did not alter cell viability, cell cycle, and growth rate of C6 glioma cells but increased their migratory capacity. Moreover, C6 cells treated with ADSC-CM showed reduced adhesion and underwent changes in cell morphology. Up-regulation of EMT-associated markers (vimentin, MMP2, and NRAS) was also observed following treatment with ADSC-CM. Our findings demonstrate that the paracrine factors released by ADSCs are able to modulate glioma cell biology. Therefore, ADSC-tumor cell interactions in a tumor microenvironment must be considered in the design of clinical application of stem cell therapy. Graphical Abstract Factors released by adipose-derived stem cells (ADSCs) may modulate the biology of C6 glioma cells. When C6 cells are exposed to a conditioned medium from adipose-derived stem cells (ADSCs-CM), some of these cells can undergo an EMT-like process and trans-differentiate into cells with a more mesenchymal phenotype, characterized by enhanced expression of EMT-related surface markers, reduced cell adhesion capacity, increased migratory capacity, as well as changes in cell and nuclei morphology.

Childhood socioeconomic position, adult socioeconomic position and social mobility in relation to markers of adiposity in early adulthood: evidence of differential effects by gender in the 1978/79 Ribeirao Preto cohort study.

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Aitsi-Selmi, A; Batty, G D; Barbieri, M A; Silva, A A M; Cardoso, V C; Goldani, M Z; Marmot, M G; Bettiol, H

2013-03-01

Longitudinal studies drawn from high-income countries demonstrate long-term associations of early childhood socioeconomic deprivation with increased adiposity in adulthood. However, there are very few data from resource-poor countries where there are reasons to anticipate different gradients. Accordingly, we sought to characterise the nature of the socioeconomic status (SES)-adiposity association in Brazil. We use data from the Ribeirao Preto Cohort Study in Brazil in which 9067 newborns were recruited via their mothers in 1978/79 and one-in-three followed up in 2002/04 (23-25years). SES, based on family income (salaries, interest on savings, pensions and so on), was assessed at birth and early adulthood, and three different adiposity measures (body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR)) ascertained at follow-up. The association between childhood SES, adult SES and social mobility (defined as four permutations of SES in childhood and adulthood: low-low, low-high, high-low, high-high), and the adiposity measures was examined using linear regression. There was evidence that the association between SES and the three markers of adiposity was modified by gender in both adulthood (P<0.02 for all outcomes) and childhood SES (P<0.02 for WC and WHR). Thus, in an unadjusted model, linear regression analyses showed that higher childhood SES was associated with lower adiposity in women (coefficient (95% confidence intervals) BMI: -1.49 (-2.29,-0.69); WC: -3.85 (-5.73,-1.97); WHR: -0.03 (-0.04,-0.02)). However, in men, higher childhood SES was related to higher adiposity (BMI: 1.03 (0.28,-1.78); WC: 3.15 (1.20, 5.09); WHR: 0.009 (-0.001, 0.019)) although statistical significance was not seen in all analyses. There was a suggestion that adult SES (but not adult health behaviours or birthweight) accounted for these relationships in women only. Upward mobility was associated with protection against greater adiposity in women but not men. In the

Label-free assessment of adipose-derived stem cell differentiation using coherent anti-Stokes Raman scattering and multiphoton microscopy

Science.gov (United States)

Mouras, Rabah; Bagnaninchi, Pierre O.; Downes, Andrew R.; Elfick, Alistair P. D.

2012-11-01

Adult stem cells (SCs) hold great potential as likely candidates for disease therapy but also as sources of differentiated human cells in vitro models of disease. In both cases, the label-free assessment of SC differentiation state is highly desirable, either as a quality-control technology ensuring cells to be used clinically are of the desired lineage or to facilitate in vitro time-course studies of cell differentiation. We investigate the potential of nonlinear optical microscopy as a minimally invasive technology to monitor the differentiation of adipose-derived stem cells (ADSCs) into adipocytes and osteoblasts. The induction of ADSCs toward these two different cell lineages was monitored simultaneously using coherent anti-Stokes Raman scattering, two photon excitation fluorescence (TPEF), and second harmonic generation at different time points. Changes in the cell's morphology, together with the appearance of biochemical markers of cell maturity were observed, such as lipid droplet accumulation for adipo-induced cells and the formation of extra-cellular matrix for osteo-induced cells. In addition, TPEF of flavoproteins was identified as a proxy for changes in cell metabolism that occurred throughout ADSC differentiation toward both osteoblasts and adipocytes. These results indicate that multimodal microscopy has significant potential as an enabling technology for the label-free investigation of SC differentiation.

Effect of adipose-derived mesenchymal stem cell transplantation on vascular calcification in rats with adenine-induced kidney disease

OpenAIRE

Yokote, Shinya; Katsuoka, Yuichi; Yamada, Akifumi; Ohkido, Ichiro; Yokoo, Takashi

2017-01-01

Previous studies have investigated the use of mesenchymal stem cells (MSCs) to treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on vascular calcification in chronic kidney disease (CKD) is still poorly understood. In the present study, we explored the potential of ASCs for the treatment of CKD and vascular calcification. CKD was induced in male Sprague-Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs transplantation significantly reduced s...

Browning of Subcutaneous White Adipose Tissue in Humans

OpenAIRE

Sidossis, Labros S.; Porter, Craig; Saraf, Manish K.; Børsheim, Elisabet; Radhakrishnan, Ravi S.; Chao, Tony; Ali, Arham; Chondronikola, Maria; Mlcak, Ronald; Finnerty, Celeste C.; Hawkins, Hal K.; Toliver-Kinsky, Tracy; Herndon, David N.

2015-01-01

Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT w...

Consumption of Sugars, Sugary Foods and Sugary Beverages in Relation to Adiposity-Related Cancer Risk in the Framingham Offspring Cohort (1991-2013).

Science.gov (United States)

Makarem, Nour; Bandera, Elisa V; Lin, Yong; Jacques, Paul; Hayes, Richard B; Parekh, Niyati

2018-04-19

Higher sugar consumption may increase cancer risk by promoting insulin-glucose dysregulation, oxidative stress, hormonal imbalances, and excess adiposity. This prospective study investigates the association between dietary sugars(fructose and sucrose) and sugary foods and beverages in relation to combined and site-specific (breast, prostate, colorectal) adiposity-associated cancers. The analytic sample consisted of 3,184 adults, aged 26-84y, from the Framingham Offspring cohort. Diet data was first collected between 1991-1995 using a food frequency questionnaire. Intakes of fructose, sucrose, sugary foods and sugary beverages (fruit juice and sugar-sweetened beverages) were derived. Participants were followed up until 2013 to ascertain cancer incidence; 565 doctor-diagnosed adiposity-related cancers, including 124 breast, 157 prostate and 68 colorectal cancers occurred. Multivariable-adjusted Cox proportional hazards models were used to evaluate associations. Tests for interaction with BMI and waist circumference were conducted. No associations were observed between fructose, sucrose, sugary food consumption and combined incidence of adiposity-related cancers or the examined site-specific cancers. While total consumption of sugary beverages was not associated with site-specific cancer risk, higher intakes of fruit juice were associated with 58% increased prostate cancer risk(HR:1.58;95%CI:1.04-2.41) in multivariable-adjusted models. In exploratory stratified analyses, higher sugary beverage intakes increased overall adiposity-related cancer risk by 59% in participants with excessive central adiposity(HR:1.59;95%CI:1.01-2.50)(p-trend=0.057). In this cohort of American adults, higher sugary beverage consumption was associated with increased cancer risk among participants with central adiposity. These analyses suggest that avoiding sugary beverages represents a simple dietary modification that may be used as an effective cancer control strategy. Copyright ©2018

Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

International Nuclear Information System (INIS)

Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

2013-01-01

To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

Energy Technology Data Exchange (ETDEWEB)

Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

2013-09-27

To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

Promoting effects of adipose-derived stem cells on breast cancer cells are reversed by radiation therapy.

Science.gov (United States)

Baaße, Annemarie; Juerß, Dajana; Reape, Elaine; Manda, Katrin; Hildebrandt, Guido

2018-04-01

Partial breast irradiation of early breast cancer patients after lumpectomy and the use of endogenous adipose tissue (AT) for breast reconstruction are promising applications to reduce the side effects of breast cancer therapy. This study tries to investigate the possible risks associated with these therapeutic approaches. It also examines the influence of adipose derived stem cells (ADSCs) as part of the breast cancer microenvironment, and endogenous AT on breast cancer cells following radiation therapy. ADSCs, isolated from human reduction mammoplasties of healthy female donors, exhibited multilineage capacity and specific surface markers. The promoting effects of ADSCs on the growth and survival fraction of breast cancer cells were reversed by treatment with high (8 Gy) or medium (2 Gy) radiation doses. In addition, a suppressing influence on breast cancer growth could be detected by co-culturing with irradiated ADSCs (8 Gy). Furthermore the clonogenic survival of unirradiated tumor cells was reduced by medium of irradiated ADSCs. In conclusion, radiation therapy changed the interactions of ADSCs and breast cancer cells. On the basis of our work, the importance of further studies to exclude potential risks of ADSCs in regenerative applications and radiotherapy has been emphasized.

Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Choi, Jane Ru; Pingguan-Murphy, Belinda; Wan Abas, Wan Abu Bakar [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Noor Azmi, Mat Adenan; Omar, Siti Zawiah [Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Chua, Kien Hui [Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia); Wan Safwani, Wan Kamarul Zaman, E-mail: wansafwani@um.edu.my [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia)

2014-05-30

Highlights: • Hypoxia maintains the stemness of adipose-derived stem cells (ASCs). • ASCs show an increased proliferation rate under low oxygen tension. • Oxygen level as low as 2% enhances the chondrogenic differentiation potential of ASCs. • HIF-1α may regulate the proliferation and differentiation activities of ASCs under hypoxia. - Abstract: Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O{sub 2} tension on their functional properties has not been well determined. In this study, we investigated the effects of O{sub 2} tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O{sub 2}) and hypoxia (2% O{sub 2}). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O{sub 2} tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.

The Role of Body Adiposity Index in Determining Body Fat Percentage in Colombian Adults with Overweight or Obesity

OpenAIRE

Robinson Ramírez-Vélez; Jorge Enrique Correa-Bautista; Katherine González-Ruíz; Alejandra Tordecilla-Sanders; Antonio García-Hermoso; Jacqueline Schmidt-RioValle; Emilio González-Jiménez

2017-01-01

The aim of this study is to investigate the accuracy of body adiposity index (BAI) as a convenient tool for assessing body fat percentage (BF%) in a sample of adults with overweight/obesity using bioelectrical impedance analysis (BIA). The study population was composed of 96 volunteers (60% female, mean age 40.6 ?? 7.5 years old). Anthropometric characteristics (body mass index, height, waist-to-height ratio, hip and waist circumference), socioeconomic status, and diet were assessed, and BF% ...

Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

Science.gov (United States)

Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

2012-03-01

Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion. Copyright © 2011 AlphaMed Press.

Generation and characterization of human iPSC line generated from mesenchymal stem cells derived from adipose tissue.

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Zapata-Linares, Natalia; Rodriguez, Saray; Mazo, Manuel; Abizanda, Gloria; Andreu, Enrique J; Barajas, Miguel; Prosper, Felipe; Rodriguez-Madoz, Juan R

2016-01-01

In this work, mesenchymal stem cells derived from adipose tissue (ADSCs) were used for the generation of the human-induced pluripotent stem cell line G15.AO. Cell reprogramming was performed using retroviral vectors containing the Yamanaka factors, and the generated G15.AO hiPSC line showed normal karyotype, silencing of the exogenous reprogramming factors, induction of the typical pluripotency-associated markers, alkaline phosphatase enzymatic activity, and in vivo and in vitro differentiation ability to the three germ layers. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration

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Marcela Fernandes

2018-01-01

Full Text Available Studies have confirmed that bone marrow-derived mesenchymal stem cells (MSCs can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs (BMSCs is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs (ADSCs have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups: sham (only sciatic nerve exposed, Matrigel (MG; sciatic nerve injury + intravenous transplantation of MG vehicle, ADSCs (sciatic nerve injury + intravenous MG containing ADSCs, and BMSCs (sciatic nerve injury + intravenous MG containing BMSCs groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury, increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios (axonal diameter/fiber diameter ratios in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for

Adipose tissue-derived stem cells in neural regenerative medicine.

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Yeh, Da-Chuan; Chan, Tzu-Min; Harn, Horng-Jyh; Chiou, Tzyy-Wen; Chen, Hsin-Shui; Lin, Zung-Sheng; Lin, Shinn-Zong

2015-01-01

Adipose tissue-derived stem cells (ADSCs) have two essential characteristics with regard to regenerative medicine: the convenient and efficient generation of large numbers of multipotent cells and in vitro proliferation without a loss of stemness. The implementation of clinical trials has prompted widespread concern regarding safety issues and has shifted research toward the therapeutic efficacy of stem cells in dealing with neural degeneration in cases such as stroke, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, cavernous nerve injury, and traumatic brain injury. Most existing studies have reported that cell therapies may be able to replenish lost cells and promote neuronal regeneration, protect neuronal survival, and play a role in overcoming permanent paralysis and loss of sensation and the recovery of neurological function. The mechanisms involved in determining therapeutic capacity remain largely unknown; however, this concept can still be classified in a methodical manner by citing current evidence. Possible mechanisms include the following: 1) the promotion of angiogenesis, 2) the induction of neuronal differentiation and neurogenesis, 3) reductions in reactive gliosis, 4) the inhibition of apoptosis, 5) the expression of neurotrophic factors, 6) immunomodulatory function, and 7) facilitating neuronal integration. In this study, several human clinical trials using ADSCs for neuronal disorders were investigated. It is suggested that ADSCs are one of the choices among various stem cells for translating into clinical application in the near future.

Immortalization of canine adipose-derived mesenchymal stem cells and their seminiferous tubule transplantation.

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Fang, Jia; Wei, Yudong; Teng, Xin; Zhao, Shanting; Hua, Jinlian

2018-04-01

Adipose-derived mesenchymal stem cells (ADSCs) are proven to provide good effects in numerous tissue engineering application and other cell-based therapies. However, the difficulty in the proliferation of ADSCs, known as the "Hayflick limit" in vitro, limits their clinical application. Here, we immortalized canine ADSCs (cADSCs) with SV40 gene and transplanted them into busulfan-induced seminiferous tubules of infertile mice. The proliferation of these immortalized cells was improved significantly. Then, cellular differentiation assays showed that the immortalized cADSCs could differentiate into three-germ-layer cells, osteogenesis, chondrogenesis, adipogenesis phenotypes, and primordial germ cell-like cells (PGCLCs). In addition, the immortalized cADSCs can proliferate in the busulfan-induced seminiferous tubules of infertile mice. These findings confirmed that the immortalized cADSCs maintain the criteria of cADSCs. © 2017 Wiley Periodicals, Inc.

Effects of melatonin on the proliferation and differentiation of rat adipose-derived stem cells

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Zaminy Arash

2008-01-01

Full Text Available Background: Osteogenesis driven by adipose-derived stem cells (ADSCs is regulated by physiological and pathological factors. Accumulating evidence from in vitro and in vivo experiments suggests that melatonin may have an influence on bone formation. However, little is known about the effects of melatonin on osteogenesis, which thus remains to be elucidated. This study was performed to determine whether melatonin at physiological concentrations (0.01-10 nM could affect the in vitro proliferation and osteogenic differentiation of rat ADSCs. Materials and Methods: ADSCs were isolated from the fat of adult rats. After cell expansion in culture media and through three passages, osteogenesis was induced in a monolayer culture using osteogenic medium with or without melatonin at physiological concentrations (0.01-10 nM. After four weeks, the cultures were examined for mineralization by Alizarin Red S and von Kossa staining and for alkaline phosphatase (ALP activity using an ALP kit. Cell viability and apoptosis were also assayed by 3-(4, 5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTT assay and flow cytometry, respectively. Results: The results indicated that at physiological concentrations, melatonin suppressed proliferation and differentiation of ADSCs. These data indicate that ADSCs exposed to melatonin, had a lower ALP activity in contrast to the cells exposed to osteogenic medium alone. Similarly, mineral deposition (calcium level also decreased in the presence of melatonin. Flow cytometry confirmed that cell growth had decreased and that the numbers of apoptotic cells had increased. Conclusion: These results suggest that the physiological concentration of melatonin has a negative effect on ADSC osteogenesis.

The adipose tissue of origin influences the biological potential of human adipose stromal cells isolated from mediastinal and subcutaneous fat depots

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Camilla Siciliano

2016-09-01

Full Text Available Indirect evidence suggests that adipose tissue-derived stromal cells (ASCs possess different physiological and biological variations related to the anatomical localization of the adipose depots. Accordingly, to investigate the influence of the tissue origin on the intrinsic properties of ASCs and to assess their response to specific stimuli, we compared the biological, functional and ultrastructural properties of two ASC pools derived from mediastinal and subcutaneous depots (thoracic compartment by means of supplements such as platelet lysate (PL and FBS. Subcutaneous ASCs exhibited higher proliferative and clonogenic abilities than mediastinal counterpart, as well as increased secreted levels of IL-6 combined with lower amount of VEGF-C. In contrast, mediastinal ASCs displayed enhanced pro-angiogenic and adipogenic differentiation properties, increased cell diameter and early autophagic processes, highlighted by electron microscopy. Our results further support the hypothesis that the origin of adipose tissue significantly defines the biological properties of ASCs, and that a homogeneric function for all ASCs cannot be assumed.

Aging and Adipose Tissue: Potential Interventions for Diabetes and Regenerative Medicine

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Palmer, Allyson K.; Kirkland, James L.

2016-01-01

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. PMID:26924669

Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

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Vikash Chandra

Full Text Available BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs to differentiate into functional islet like cell aggregates (ICAs. Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17 and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes.

Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

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Kamila Wojciechowicz

Full Text Available The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16 the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis, under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

Effects of RF-EMF Exposure from GSM Mobile Phones on Proliferation Rate of Human Adipose-derived Stem Cells: An In-vitro Study

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Shahbazi-Gahrouei D

2016-12-01

Full Text Available Background: As the use of mobile phones is increasing, public concern about the harmful effects of radiation emitted by these devices is also growing. In addition, protection questions and biological effects are among growing concerns which have remained largely unanswered. Stem cells are useful models to assess the effects of radiofrequency electromagnetic fields (RF-EMF on other cell lines. Stem cells are undifferentiated biological cells that can differentiate into specialized cells. Adipose tissue represents an abundant and accessible source of adult stem cells. The aim of this study is to investigate the effects of GSM 900 MHz on growth and proliferation of mesenchymal stem cells derived from adipose tissue within the specific distance and intensity. Materials and Methods: ADSCs were exposed to GSM mobile phones 900 MHz with intensity of 354.6 µW/cm2 square waves (217 Hz pulse frequency, 50% duty cycle, during different exposure times ranging from 6 to 21 min/day for 5 days at 20 cm distance from the antenna. MTT assay was used to determine the growth and metabolism of cells and trypan blue test was also done for cell viability. Statistical analyses were carried out using analysis of one way ANOVA. P<0.05 was considered to be statistically significant. Results: The proliferation rates of human ADSCs in all exposure groups were significantly lower than control groups (P<0.05 except in the group of 6 minutes/day which did not show any significant difference with control groups. Conclusion: The results show that 900 MHz RF signal radiation from antenna can reduce cell viability and proliferation rates of human ADSCs regarding the duration of exposure.

Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade.

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Sawada, Yoko; Sakamoto, Yuri; Toh, Mariko; Ohara, Nozomi; Hatanaka, Yuiko; Naka, Ayano; Kishimoto, Yoshimi; Kondo, Kazuo; Iida, Kaoruko

2015-12-01

This study aimed to examine the effects of Val-Pro-Pro (VPP), a food-derived peptide with an angiotensin-converting enzyme (ACE) inhibitory property, on obesity-linked insulin resistance, and adipose inflammation in vivo and in vitro. C57BL/6J mice were fed high-fat high-sucrose diet and VPP (0.1% in water) for 4 months. For in vitro analysis, coculture of 3T3-L1 adipocytes overexpressing either ACE (3T3-ACE) or green fluorescent protein (3T3-GFP) and RAW264 macrophages was conducted with VPP. In diet-induced obese mice, VPP improved insulin sensitivity, concomitant with a significant decrease in tumor necrosis factor α (TNF-α) and IL-1β expression in adipose tissue, with a tendency (p = 0.06) toward decreased CC chemokine ligand 5 expression. Additionally, VPP administration inhibited macrophage accumulation and activation in fat tissues. In vitro, VPP attenuated TNF-α mRNA induced by ACE overexpression in 3T3-L1 adipocytes. TNF-α and IL-1β expression decreased following VPP treatment of RAW264 macrophage and 3T3-ACE adipocyte cocultures, but not in RAW264-3T3-GFP adipocyte cocultures. Our data suggest that VPP inhibits adipose inflammation in the interaction between adipocytes and macrophages, acting as an ACE inhibitor, thereby improving obesity-related insulin resistance. Thus, ingestion of VPP may be a viable protective and therapeutic strategy for insulin resistance and obesity-associated adipose inflammation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues

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Liaw, Lucy; Prudovsky, Igor; Koza, Robert A.; Anunciado-Koza, Rea V.; Siviski, Matthew E.; Lindner, Volkhard; Friesel, Robert E.; Rosen, Clifford J.; Baker, Paul R.S.; Simons, Brigitte; Vary, Calvin P.H.

2016-01-01

Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MSALL. Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-...

Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.

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Alfadda, Assim A; Sallam, Reem M; Chishti, Muhammad Azhar; Moustafa, Amr S; Fatma, Sumbul; Alomaim, Waleed S; Al-Naami, Mohammed Y; Bassas, Abdulelah F; Chrousos, George P; Jo, Hyunsun

2012-06-01

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.

Effects of external radiation in a co-culture model of endothelial cells and adipose-derived stem cells

International Nuclear Information System (INIS)

Haubner, Frank; Leyh, Michaela; Ohmann, Elisabeth; Pohl, Fabian; Prantl, Lukas; Gassner, Holger G

2013-01-01

The inflammatory response clinically observed after radiation has been described to correlate with elevated expression of cytokines and adhesion molecules by endothelial cells. Therapeutic compensation for this microvascular compromise could be an important approach in the treatment of irradiated wounds. Clinical reports describe the potential of adipose-derived stem cells to enhance wound healing, but the underlying cellular mechanisms remain largely unclear. Human dermal microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with sequential doses of 2 to 12 Gy. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the supernatants using enzyme-linked immunosorbent assay (ELISA). Irradiated HDMEC and ASC as well as non-irradiated co-cultures, HDMEC or ASC respectively were used as controls. Cell count was significantly reduced in irradiated co-cultures of HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC. The increased expression of cytokines and adhesion molecules by HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds

The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

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Marijana Todorčević

2015-12-01

Full Text Available Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3 and docosahexaenoic acid (DHA; 22:6n-3. Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity.

Long-term MRI tracking of dual-labeled adipose-derived stem cells homing into mouse carotid artery injury

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Qin JB

2012-10-01

Full Text Available Jin-Bao Qin,1,5,* Kang-An Li,2,* Xiang-Xiang Li,1,5 Qing-Song Xie,3 Jia-Ying Lin,4 Kai-Chuang Ye,1,5 Mi-Er Jiang,1,5 Gui-Xiang Zhang,2 Xin-Wu Lu1,51Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 2Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Department of Neurosurgery, Cixi Municipal People's Hospital, Zhejiang Province, China; 4Clinic for Gynecology, Charite-Universitatsmedizin Berlin, Berlin, Germany; 5Vascular Center, Shanghai Jiao Tong University, Shanghai, China*These two authors contributed equally to this workBackground: Stem cell therapy has shown great promise for regenerative repair of injured or diseased tissues. Adipose-derived stem cells (ADSCs have become increasingly attractive candidates for cellular therapy. Magnetic resonance imaging has been proven to be effective in tracking magnetic-labeled cells and evaluating their clinical relevance after cell transplantation. This study investigated the feasibility of imaging green fluorescent protein-expressing ADSCs (GFP-ADSCs labeled with superparamagnetic iron oxide particles, and tracked them in vivo with noninvasive magnetic resonance imaging after cell transplantation in a model of mouse carotid artery injury.Methods: GFP-ADSCs were isolated from the adipose tissues of GFP mice and labeled with superparamagnetic iron oxide particles. Intracellular stability, proliferation, and viability of the labeled cells were evaluated in vitro. Next, the cells were transplanted into a mouse carotid artery injury model. Clinical 3 T magnetic resonance imaging was performed immediately before and 1, 3, 7, 14, 21, and 30 days after cell transplantation. Prussian blue staining and histological analysis were performed 7 and 30 days after transplantation.Results: GFP-ADSCs were found to be efficiently labeled with superparamagnetic iron oxide

Gold nanoparticles promote osteogenic differentiation in human adipose-derived mesenchymal stem cells through the Wnt/β-catenin signaling pathway

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Choi SY

2015-07-01

Full Text Available Seon Young Choi,1 Min Seok Song,1 Pan Dong Ryu,1 Anh Thu Ngoc Lam,2 Sang-Woo Joo,2 So Yeong Lee1 1Laboratory of Veterinary Pharmacology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 2Department of Chemistry, Soongsil University, Seoul, South Korea Abstract: Gold nanoparticles (AuNPs are attractive materials for use in biomedicine due to their physical properties. Increasing evidence suggests that several nanoparticles induce the differentiation of human mesenchymal stem cells into osteoblasts and adipocytes. In this study, we hypothesized that chitosan-conjugated AuNPs promote the osteogenic differentiation of human adipose-derived mesenchymal stem cells. For the evaluation of osteogenic differentiation, alizarin red staining, an alamarBlue® assay, and a quantitative real-time polymerase chain reaction analysis were performed. In order to examine specific signaling pathways, immunofluorescence and a western blotting assay were performed. Our results demonstrate that chitosan-conjugated AuNPs increase the deposition of calcium content and the expression of marker genes related to osteogenic differentiation in human adipose-derived mesenchymal stem cells at nontoxic concentrations. These results indicate that chitosan-conjugated AuNPs promote osteogenesis through the Wnt/β-catenin signaling pathway. Therefore, chitosan-conjugated AuNPs can be used as a reagent for promoting bone formation. Keywords: chitosan-conjugated gold nanoparticle, mineralization, nonphosphorylated beta-catenin

The Use of Adipose Derived Progenitor Cells and Platelet Rich Plasma Combination for the Treatment of Supraspinatus Tendinopathy in 55 Dogs: A Retrospective Study

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Sherman Orye Canapp

2016-09-01

Full Text Available Objective: To report clinical findings and outcomes for 55 dogs with supraspinatus tendinopathy treated with adipose derived progenitor cells and platelet rich plasma therapy.Methods: Medical records of client-owned dogs diagnosed with supraspinatus tendinopathy that were treated with adipose derived progenitor cells and platelet rich plasma (ADPC-PRP combination therapy were reviewed from 2006-2013. Data collected included signalment, medical history, limb involvement, prior treatments, physical and orthopedic examination, objective temporospatial gait analysis findings, diagnostic imaging results (radiography, magnetic resonance imaging, musculoskeletal ultrasonography, arthroscopy findings, and outcome. Results: Following ultrasound-guided injection of ADPC-PRP, objective gait analysis was available on 25 of the 55 dogs at 90 days post ADPC-PRP therapy. Following treatment, a significant increase in total pressure index percentage (TPI% was noted in the injured (treated forelimb at 90 days post treatment (p = 0.036. At 90 days following treatment, 88% of cases had no significant difference in TPI% of the injured limb to the contralateral limb. The remaining 12% of cases had significantly improved (p=0.036. Bilateral shoulder diagnostic musculoskeletal ultrasound revealed a significant reduction in tendon size (CSA in the treated tendon at 90 days following treatment when compared to the initial CSA (p=0.005. All cases showed significant improvement in fiber pattern of the affected supraspinatus tendon by the ultrasound shoulder pathology rating scale.Clinical Relevance: These findings suggest that ADPC-PRP therapy should be considered for dogs with supraspinatus tendinopathy.Abbreviations:ST: supraspinatus tendinopathyADPC: adipose derived progenitor cellsMSC: mesenchymal stem cellsPRP: platelet rich plasmaTPI%: total pressure index percentage

Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure

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Kastrup, Jens; Schou, Morten; Gustafsson, Ida

2017-01-01

BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems...

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

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Qi, Dianjun; Wu, Shaohua; Kuss, Mitchell A; Shi, Wen; Chung, Soonkyu; Deegan, Paul T; Kamenskiy, Alexey; He, Yini; Duan, Bin

2018-05-26

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic

Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy

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Haahr, Martha Kirstine; Jensen, Charlotte Harken; Toyserkani, Navid Mohamadpour

2016-01-01

BACKGROUND: Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condi......BACKGROUND: Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory...... and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. METHODS: Seventeen...... men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5-18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed...

Surgical sutures filled with adipose-derived stem cells promote wound healing.

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Ann Katharin Reckhenrich

Full Text Available Delayed wound healing and scar formation are among the most frequent complications after surgical interventions. Although biodegradable surgical sutures present an excellent drug delivery opportunity, their primary function is tissue fixation. Mesenchymal stem cells (MSC act as trophic mediators and are successful in activating biomaterials. Here biodegradable sutures were filled with adipose-derived mesenchymal stem cells (ASC to provide a pro-regenerative environment at the injured site. Results showed that after filling, ASCs attach to the suture material, distribute equally throughout the filaments, and remain viable in the suture. Among a broad panel of cytokines, cell-filled sutures constantly release vascular endothelial growth factor to supernatants. Such conditioned media was evaluated in an in vitro wound healing assay and showed a significant decrease in the open wound area compared to controls. After suturing in an ex vivo wound model, cells remained in the suture and maintained their metabolic activity. Furthermore, cell-filled sutures can be cryopreserved without losing their viability. This study presents an innovative approach to equip surgical sutures with pro-regenerative features and allows the treatment and fixation of wounds in one step, therefore representing a promising tool to promote wound healing after injury.

Transplantation of Adipose Derived Stromal Cells into the Developing Mouse Eye

International Nuclear Information System (INIS)

Yu, Song-Hee; Jang, Yu-Jin; Lee, Eun-Shil; Hwang, Dong-Youn; Jeon, Chang-Jin

2010-01-01

Adipose derived stromal cells (ADSCs) were transplanted into a developing mouse eye to investigate the influence of a developing host micro environment on integration and differentiation. Green fluorescent protein-expressing ADSCs were transplanted by intraocular injections. The age of the mouse was in the range of 1 to 10 days postnatal (PN). Survival dates ranged from 7 to 28 post transplantation (DPT), at which time immunohistochemistry was performed. The transplanted ADSCs displayed some morphological differentiations in the host eye. Some cells expressed microtubule associated protein 2 (marker for mature neuron), or glial fibrillary acid protein (marker for glial cell). In addition, some cells integrated into the ganglion cell layer. The integration and differentiation of the transplanted ADSCs in the 5 and 10 PN 7 DPT were better than in the host eye the other age ranges. This study was aimed at demonstrating how the age of host micro environment would influence the differentiation and integration of the transplanted ADSCs. However, it was found that the integration and differentiation into the developing retina were very limited when compared with other stem cells, such as murine brain progenitor cell

Comparative effects on type 2 diabetes of mesenchymal stem cells derived from bone marrow and adipose tissue

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Li ZANG

2016-08-01

Full Text Available Objective 　To compare the effects on type 2 diabetes of mesenchymal stem cells (MSCs derived from bone marrow and adipose tissue. Methods 　Thirty type 2 diabetic rat models were established by an eight weeks high-fat diet (HFD with a low dose streptozotocin (STZ, 25mg/kg, and randomly assigned into three groups (10 each: diabetes group (T2DM, bone marrow MSCs transplantation group (BMSC and adipose tissue MSCs transplantation group (ADSC. Ten normal rats were set as control. MSCs were isolated from bone marrow or inguinal adipose tissue of normal rats. One week after STZ injection, 3×10 6 MSCs suspended in 1ml PBS were infused into rats via tail vein. The blood glucose was measured every day after MSCs transplantation, the intraperitoneal glucose tolerance test (IPGTT and intraperitoneal insulin tolerance test (IPITT were performed the 7th day after transplantation to evaluate the effects of MSCs on diabetic rats. Pancreatic tissues were collected for insulin/glucagon immunofluorescence staining. Results 　After MSCs transplantation, the blood glucose decreased gradually and continuously in type 2 diabetic rats, with glucose tolerance and insulin sensitivity improved greatly. The improved insulin sensitivity was further confirmed by a decreased HOMA-IR (homeostasis model of assessment for insulin resistance index and increased pancreas islet β-cells (P<0.05. However, no significant differences were observed between BMSC and ADSC group. Conclusion 　Both BMSC and ADSC have the same effect on type 2 diabetic rats, so the ADSC will be the ideal stem cells for treatment of type 2 diabetes. DOI: 10.11855/j.issn.0577-7402.2016.07.03

Physical Activity and Adiposity Markers at Older Ages: Accelerometer Vs Questionnaire Data

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Sabia, Séverine; Cogranne, Pol; van Hees, Vincent T.; Bell, Joshua A.; Elbaz, Alexis; Kivimaki, Mika; Singh-Manoux, Archana

2015-01-01

Objective Physical activity is critically important for successful aging, but its effect on adiposity markers at older ages is unclear as much of the evidence comes from self-reported data on physical activity. We assessed the associations of questionnaire-assessed and accelerometer-assessed physical activity with adiposity markers in older adults. Design/Setting/Participants This was a cross-sectional study on 3940 participants (age range 60-83 years) of the Whitehall II study who completed a 20-item physical activity questionnaire and wore a wrist-mounted accelerometer for 9 days in 2012 and 2013. Measurements Total physical activity was estimated using metabolic equivalent hours/week for the questionnaire and mean acceleration for the accelerometer. Time spent in moderate-and-vigorous physical activity (MVPA) was also assessed by questionnaire and accelerometer. Adiposity assessment included body mass index, waist circumference, and fat mass index. Fat mass index was calculated as fat mass/height² (kg/m²), with fat mass estimated using bioimpedance. Results Greater total physical activity was associated with lower adiposity for all adiposity markers in a dose-response manner. In men, the strength of this association was 2.4 to 2.8 times stronger with the accelerometer than with questionnaire data. In women, it was 1.9 to 2.3 times stronger. For MVPA, questionnaire data in men suggested no further benefit for adiposity markers past 1 hour/week of activity. This was not the case for accelerometer-assessed MVPA where, for example, compared with men undertaking physical activity with adiposity markers in older adults was stronger when physical activity was assessed by accelerometer compared with questionnaire, suggesting that physical activity might be more important for adiposity than previously estimated. PMID:25752539

Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity.

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Park, S; Park, H-L; Lee, S-Y; Nam, J-H

2016-03-01

Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied. Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO. In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection. These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

Preventive effects of CTLA4Ig-overexpressing adipose tissue--derived mesenchymal stromal cells in rheumatoid arthritis.

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Choi, Eun Wha; Yun, Tae Won; Song, Ji Woo; Lee, Minjae; Yang, Jehoon; Choi, Kyu-Sil

2015-03-01

Rheumatoid arthritis is a systemic autoimmune disorder. In this study, we first compared the therapeutic effects of syngeneic and xenogeneic adipose tissue-derived stem cells on a collagen-induced arthritis mouse model. Second, we investigated the synergistic preventive effects of CTLA4Ig and adipose tissue-derived mesenchymal stromal cells (ASCs) as a therapeutic substance. Arthritis was induced in all groups except for the normal, saline (N) group, using chicken type II collagen (CII). Animals were divided into C (control, saline), H (hASCs), M (mASCs) and N groups (experiment I) and C, H, CT (CTLA4Ig-overexpressing human ASC [CTLA4Ig-hASCs]) and N groups (experiment II), according to transplanted material. Approximately 2 × 10(6) ASCs or 150 μL of saline was intravenously administered on days 24, 27, 30 and 34, and all animals were killed on days 42 to 44 after CII immunization. Anti-mouse CII autoantibodies were significantly lower in the H, M and CT groups than in the C group. Cartilage damage severity score and C-telopeptide of type II collagen were significantly lower in the CT group than in the C group. The serum levels of IL-6 were significantly lower in the H, M and CT groups than in the C group. The serum levels of keratinocyte chemoattractant were significantly lower in the CT group than the C group. There were similar effects of ASCs on the decrease of anti-mouse CII autoantibody levels between syngeneic and xenogeneic transplantations, and CTLA4Ig-hASCs showed synergistic preventive effects compared with non-transduced hASCs. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Therapeutic Effect of Ligustilide-Stimulated Adipose-Derived Stem Cells in a Mouse Thromboembolic Stroke Model.

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Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Lin, Shinn-Zong; Huang, Pi-Chun; Lin, Po-Cheng; Chang, Fu-Kuei; Liu, Shih-Ping

2016-01-01

Stroke is a result of cerebral ischemia that triggers a cascade of both physiological and biochemical events. No effective treatment is available for stroke; however, stem cells have the potential to rescue tissue from the effects of stroke. Adipose-derived stem cells (ADSCs) are an abundant source of adult stem cells; therefore, ADSC therapy can be considered as a future strategy for regenerative medicine. However, more research is required to improve the effectiveness of transplanted ADSCs as a treatment for stroke in the mouse stroke model. Ligustilide, isolated from the herb Angelica sinensis, exhibits a protective effect on neurons and inhibits inflammation. We also demonstrated that ligustilide treatment increases the expression levels of homing factors such as SDF-1 and CXCR4. In the present study, we evaluated the therapeutic effects of ADSC transplantation and ligustilide treatment in a mouse thromboembolic stroke model by behavioral tests, including beam walking, locomotor activity, and rotarod analysis. ADSCs pretreated with ligustilide were transplanted into the brains of stroke mice. The results showed that the therapeutic effect of ADSCs pretreated with ligustilide was better than that of ADSCs without ligustilide pretreatment. There was no difference between the recovery of mice treated by ADSC transplantation combined with subcutaneous ligustilide injection and that of mice treated only with ADSCs. The TUNEL assay showed fewer apoptotic cells in the brains of mice transplanted with ADSCs pretreated with ligustilide as well as in those without pretreatment. In summary, pretreatment of ADSCs with ligustilide improves the therapeutic efficacy of ADSC transplantation. The results of this study will help improve stem cell therapies being developed for future clinical applications.

Leptin differentially regulates STAT3 activation in the ob/ob mice adipose mesenchymal stem cells

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Leptin-deficient genetically obese ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Studies have shown that multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute...

Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

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María Teresa Ramírez-López

Full Text Available Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS. In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a the adult expression of endocannabinoid-related behaviors, b the metabolic profile of adult offspring and c the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

Osteogenic capability of autologous rabbit adipose-derived stromal cells in repairing calvarial defects.

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Cheng, Shao-Wen; Lin, Zhong-Qin; Wang, Wei; Zhang, Wei; Kou, Dong-Quan; Ying, Xiao-Zhou; Chen, Qing-Yu; Shen, Yue; Cheng, Xiao-Jie; Peng, Lei; Lv, Chuan-Zhu

2011-01-01

To evaluate the in vitro and in vivo osteogenic capability of adipose-derived stromal cells (ASCs). ASCs were isolated from New Zealand white rabbits and determined by alkaline phosphatase (ALP) staining, von Kossa staining and alizarin red staining. Some specific markers of osteogenic differentiation, including ALP, osteocalcin (OCN), osteopontin (OPN) were examined by reverse transcription-polymerase chain reaction (RT-PCR). In vivo, demineralized bone matrix (DBM)-ASCs composites were implanted into the rabbit calvarial defects created at each side of the longitudinal midline. After 6 weeks, histologic properties of the transplants were analyzed. ASCs were successfully induced into osteogenesis. ALP staining, von Kossa staining and alizarin red staining showed positive results. The expressions of ALP, OCN and OPN were detected in ASCs after cultivation in osteogenic medium. Extensive new bone was observed in the defects transplanted with DBM-ASCs composites. ASCs have the potential to differentiate into osteogenic lineage and DBM-ASCs constructs are a promising method for regeneration in bone defects.

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

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Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

2018-02-06

Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver.

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Gotoh, Koro; Inoue, Megumi; Masaki, Takayuki; Chiba, Seiichi; Shimasaki, Takanobu; Ando, Hisae; Fujiwara, Kansuke; Katsuragi, Isao; Kakuma, Tetsuya; Seike, Masataka; Sakata, Toshiie; Yoshimatsu, Hironobu

2012-08-01

Obesity is associated with systemic low-grade inflammation and obesity-related metabolic disorders. Considering that obesity decreases the expression of proinflammatory cytokines in the spleen, we assessed the role of interleukin (IL)-10, an anti-inflammatory cytokine produced by the spleen, in the pathogenesis of obesity. Changes in obesity-related pathogenesis, including inflammatory responses in multiple organs, were assessed after systemic administration of exogenous IL-10 to splenectomy (SPX)-treated obese wild-type and IL-10 knockout (IL-10KO) mice. Obesity resulted in the inability of the spleen to synthesize cytokines, including IL-10, and proinflammatory cytokines in obesity are then likely to emerge from tissues other than the spleen because serum levels of IL-10, but not proinflammatory cytokines, decreased despite the expression of these cytokines in the spleen being reduced in high fat-induced obese mice. SPX aggravated the inflammatory response in white adipose tissue (WAT) and the liver and suppressed adiposity in WAT. However, it accentuated adiposity in the liver. These SPX-induced changes were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on the inflammatory responses in WAT and the liver of IL-10KO mice. These data show the role of spleen-derived IL-10 in diet-induced changes as a result of inflammatory responses in WAT and the liver.

Adiposity and height of adult Hmong refugees: relationship with war-related early malnutrition and later migration.

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Clarkin, Patrick F

2008-01-01

This study investigated whether historical proxies for poor nutrition early in life were associated with differences in body composition and height among adult Hmong refugees. Life history and anthropometric data were collected from a sample of 279 Hmong aged 18-51 years who were born in Laos or Thailand and resettled in French Guiana or the United States following the Second Indochina War. Overall, 30.5% were born in a war zone in Laos, while 38.8% were displaced as infants; these individuals were presumed to have experienced malnutrition in the perinatal and infant periods, respectively. Resettlement in urban areas in the US was utilized as a proxy for greater exposure to excessive energy balance, compared with Hmong who resettled in rural areas in French Guiana. In multiple linear regression models, being displaced in infancy was negatively associated with height after controlling for confounders, while being born in a war zone was associated with higher adiposity and centralized body fat distribution. Resettlement in the US was associated with a higher centralization of subcutaneous fat, but not overall adiposity. These findings may be of interest to the study of the developmental origins of obesity, in a population that has undergone early malnutrition followed by migration and rapid nutritional transition.

Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity.

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Luisa Bonet, M; Canas, Jose A; Ribot, Joan; Palou, Andreu

2015-04-15

A novel perspective of the function of carotenoids and carotenoid-derived products - including, but not restricted to, the retinoids - is emerging in recent years which connects these compounds to the control of adipocyte biology and body fat accumulation, with implications for the management of obesity, diabetes and cardiovascular disease. Cell and animal studies indicate that carotenoids and carotenoids derivatives can reduce adiposity and impact key aspects of adipose tissue biology including adipocyte differentiation, hypertrophy, capacity for fatty acid oxidation and thermogenesis (including browning of white adipose tissue) and secretory function. Epidemiological studies in humans associate higher dietary intakes and serum levels of carotenoids with decreased adiposity. Specifically designed human intervention studies, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. The objective of this review is to summarize recent findings in this area, place them in physiological contexts, and provide likely regulatory schemes whenever possible. The focus will be on the effects of carotenoids as nutritional regulators of adipose tissue biology and both animal and human studies, which support a role of carotenoids and retinoids in the prevention of abdominal adiposity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The Associations Between Increasing Degrees of HOMA-IR and Measurements of Adiposity Among Euglycemic U.S. Adults.

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Boyer, William R; Johnson, Tammie M; Fitzhugh, Eugene C; Richardson, Michael R; Churilla, James R

2016-03-01

The purpose of this study was to examine the associations between increasing degrees of insulin resistance (using the homeostatic model assessment of insulin resistance [HOMA-IR]) and two measures of adiposity in a nationally representative sample of euglycemic U.S. adults. Sample included adult participants (≥ 20 years of age) [N = 1586 (body mass index, BMI model), N = 1577 (waist circumference, WC model)] from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). HOMA-IR was categorized into quartiles. BMI and WC were examined continuously as the dependent variables. Following adjustment for covariates, those with HOMA-IR values in the second, third, and fourth quartiles had significantly higher BMIs (P HOMA-IR (P HOMA-IR and BMI (R(2) = 0.4171, P HOMA-IR and WC (R(2) = 0.4826, P HOMA-IR value is associated with higher BMI and WC values in euglycemic subjects.

Road Traffic and Railway Noise Exposures and Adiposity in Adults

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Christensen, Jeppe S; Raaschou-Nielsen, Ole; Tjønneland, Anne

2016-01-01

and railway noise and adiposity. METHODS: In this cross-sectional study of 57,053 middle-aged people, height, weight, waist circumference, and bioelectrical impedance were measured at enrollment (1993-1997). Body mass index (BMI), body fat mass index (BFMI), and lean body mass index (LBMI) were calculated....... Residential exposure to road and railway traffic noise exposure was calculated using the Nordic prediction method. Associations between traffic noise and anthropometric measures at enrollment were analyzed using general linear models and logistic regression adjusted for demographic and lifestyle factors......, significant increases were also found for BFMI and LBMI. All associations followed linear exposure-response relationships. Exposure to railway noise was not linearly associated with adiposity measures. However, exposure > 60 dB was associated with a 0.71-cm wider waist circumference (95% CI: 0.23, 1...

Adipose-Derived Stromal Cells for Treatment of Patients with Chronic Ischemic Heart Disease (MyStromalCell Trial)

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Qayyum, Abbas Ali; Mathiasen, Anders Bruun; Mygind, Naja Dam

2017-01-01

We aimed to evaluate the effect of intramyocardial injections of autologous VEGF-A165-stimulated adipose-derived stromal cells (ASCs) in patients with refractory angina. MyStromalCell trial is a randomized double-blind placebo-controlled study including sixty patients with CCS/NYHA class II...... to 54) (P= 0.41), and in METs 0.1 (95%CI -1.7 to 1.9) (P= 0.757). The difference between the groups was not significant (P= 0.680,P= 0.608, andP= 0.720 for time duration, watt, and METs, resp.). Intramyocardial delivered VEGF-A165-stimulated ASC treatment was safe but did not improve exercise capacity...

Low-frequency, low-magnitude vibrations (LFLM enhances chondrogenic differentiation potential of human adipose derived mesenchymal stromal stem cells (hASCs

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Krzysztof Marycz

2016-02-01

Full Text Available The aim of this study was to evaluate if low-frequency, low-magnitude vibrations (LFLM could enhance chondrogenic differentiation potential of human adipose derived mesenchymal stem cells (hASCs with simultaneous inhibition of their adipogenic properties for biomedical purposes. We developed a prototype device that induces low-magnitude (0.3 g low-frequency vibrations with the following frequencies: 25, 35 and 45 Hz. Afterwards, we used human adipose derived mesenchymal stem cell (hASCS, to investigate their cellular response to the mechanical signals. We have also evaluated hASCs morphological and proliferative activity changes in response to each frequency. Induction of chondrogenesis in hASCs, under the influence of a 35 Hz signal leads to most effective and stable cartilaginous tissue formation through highest secretion of Bone Morphogenetic Protein 2 (BMP-2, and Collagen type II, with low concentration of Collagen type I. These results correlated well with appropriate gene expression level. Simultaneously, we observed significant up-regulation of α3, α4, β1 and β3 integrins in chondroblast progenitor cells treated with 35 Hz vibrations, as well as Sox-9. Interestingly, we noticed that application of 35 Hz frequencies significantly inhibited adipogenesis of hASCs. The obtained results suggest that application of LFLM vibrations together with stem cell therapy might be a promising tool in cartilage regeneration.

Translational applications of adult stem cell-derived organoids

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Drost, Jarno; Clevers, Hans

2017-01-01

Adult stem cells from a variety of organs can be expanded long-term in vitro as three-dimensional organotypic structures termed organoids. These adult stem cell-derived organoids retain their organ identity and remain genetically stable over long periods of time. The ability to grow organoids from

A 3D Porous Gelatin-Alginate-Based-IPN Acts as an Efficient Promoter of Chondrogenesis from Human Adipose-Derived Stem Cells

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Dinescu, Sorina; Galateanu, Bianca; Radu, Eugen; Hermenean, Anca; Lungu, Adriana; Stancu, Izabela Cristina; Jianu, Dana; Tumbar, Tudorita; Costache, Marieta

2015-01-01

Cartilage has limited regeneration potential. Thus, there is an imperative need to develop new strategies for cartilage tissue engineering (CTE) amenable for clinical use. Recent CTE approaches rely on optimal cell-scaffold interactions, which require a great deal of optimization. In this study we attempt to build a novel gelatin- (G-) alginate- (A-) polyacrylamide (PAA) 3D interpenetrating network (IPN) with superior performance in promoting chondrogenesis from human adipose-derived stem cel...

Sericin Enhances the Bioperformance of Collagen-Based Matrices Preseeded with Human-Adipose Derived Stem Cells (hADSCs

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Marieta Costache

2013-01-01

Full Text Available Current clinical strategies for adipose tissue engineering (ATE, including autologous fat implants or the use of synthetic surrogates, not only are failing in the long term, but also can’t face the latest requirements regarding the aesthetic restoration of the resulted imperfections. In this context, modern strategies in current ATE applications are based on the implantation of 3D cell-scaffold bioconstructs, designed for prospective achievement of in situ functional de novo tissue. Thus, in this paper, we reported for the first time the evaluation of a spongious 60% collagen and 40% sericin scaffold preseeded with human adipose-derived stem cells (hADSCs in terms of biocompatibility and adipogenic potential in vitro. We showed that the addition of the sticky protein sericin in the composition of a classical collagen sponge enhanced the adhesion and also the proliferation rate of the seeded cells, thus improving the biocompatibility of the novel scaffold. In addition, sericin stimulated PPARγ2 overexpression, triggering a subsequent upregulated expression profile of FAS, aP2 and perilipin adipogenic markers. These features, together with the already known sericin stimulatory potential on cellular collagen production, promote collagen-sericin biomatrix as a good candidate for soft tissue reconstruction and wound healing applications.

Dietary sodium, adiposity, and inflammation in healthy adolescents.

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Zhu, Haidong; Pollock, Norman K; Kotak, Ishita; Gutin, Bernard; Wang, Xiaoling; Bhagatwala, Jigar; Parikh, Samip; Harshfield, Gregory A; Dong, Yanbin

2014-03-01

To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents. A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1. The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption.

Transcriptomic comparisons between cultured human adipose tissue-derived pericytes and mesenchymal stromal cells

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Lindolfo da Silva Meirelles

2016-03-01

Full Text Available Mesenchymal stromal cells (MSCs, sometimes called mesenchymal stem cells, are cultured cells able to give rise to mature mesenchymal cells such as adipocytes, osteoblasts, and chondrocytes, and to secrete a wide range of trophic and immunomodulatory molecules. Evidence indicates that pericytes, cells that surround and maintain physical connections with endothelial cells in blood vessels, can give rise to MSCs (da Silva Meirelles et al., 2008 [1]; Caplan and Correa, 2011 [2]. We have compared the transcriptomes of highly purified, human adipose tissue pericytes subjected to culture-expansion in pericyte medium or MSC medium, with that of human adipose tissue MSCs isolated with traditional methods to test the hypothesis that their transcriptomes are similar (da Silva Meirelles et al., 2015 [3]. Here, we provide further information and analyses of microarray data from three pericyte populations cultured in pericyte medium, three pericyte populations cultured in MSC medium, and three adipose tissue MSC populations deposited in the Gene Expression Omnibus under accession number GSE67747. Keywords: Mesenchymal stromal cells, Mesenchymal stem cells, Pericytes, Microarrays

The Effects of Environmental Factors on Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells and Esophagus Tissues Engineering

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Wang, Fang

Adipose-derived stem cells (ASCs) are increasingly being used for regenerative medicine and tissue engineering. Smooth muscle cells (SMCs) can be differentiated from ASCs. Oxygen is a key factor influencing the stem cell differentiation. Tissue engineered esophagus has been a preferred solution...... of esophagus was studied. Our results showed that both SMCs and ASCs could attach on the porcine esophageal acellular matrix (EAM) scaffold in vitro after 24 hours and survive until 7 days. Thus ASCs might be a substitute for SMCs in the construction of tissue engineered esophageal muscle layer....

Effects of initiating moderate wine intake on abdominal adipose tissue in adults with type 2 diabetes: a 2-year randomized controlled trial.

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Golan, Rachel; Shelef, Ilan; Shemesh, Elad; Henkin, Yaakov; Schwarzfuchs, Dan; Gepner, Yftach; Harman-Boehm, Ilana; Witkow, Shula; Friger, Michael; Chassidim, Yoash; Liberty, Idit F; Sarusi, Benjamin; Serfaty, Dana; Bril, Nitzan; Rein, Michal; Cohen, Noa; Ben-Avraham, Sivan; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Thiery, Joachim; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2017-02-01

To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes. In the 2-year randomized controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI. Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel. Alcohol-abstaining adults with well-controlled type 2 diabetes. Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Changes (95 % CI) in abdominal adipose-tissue distribution were similar: red wine, visceral adipose tissue (VAT) -3·0 (-8·0, 2·0) %, deep subcutaneous adipose tissue (DSAT) +5·2 (-1·1, 11·6) %, superficial subcutaneous adipose tissue (SSAT) -1·9 (-5·0, 1·2) %; water, VAT -3·2 (-8·9, 2·5) %, DSAT +2·9 (-2·8, 8·6) %, SSAT -0·15 (-3·3, 2·9) %. No changes in antidiabetic medication and no substantial changes in energy intake (+126 (sd 2889) kJ/d (+30·2 (sd 690) kcal/d), P=0·8) were recorded. A 2-year decrease in glycated Hb (β=0·28, P=0·05) was associated with a decrease in VAT. Moderate wine consumption, as part of a Mediterranean diet, in persons with controlled diabetes did not promote weight gain or abdominal adiposity.

Comparison of the relationship between bone marrow adipose tissue and volumetric bone mineral density in children and adults.

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Shen, Wei; Velasquez, Gilbert; Chen, Jun; Jin, Ye; Heymsfield, Steven B; Gallagher, Dympna; Pi-Sunyer, F Xavier

2014-01-01

Several large-scale studies have reported the presence of an inverse relationship between bone mineral density (BMD) and bone marrow adipose tissue (BMAT) in adults. We aim to determine if there is an inverse relationship between pelvic volumetric BMD (vBMD) and pelvic BMAT in children and to compare this relationship in children and adults. Pelvic BMAT and bone volume (BV) was evaluated in 181 healthy children (5-17yr) and 495 healthy adults (≥18yr) with whole-body magnetic resonance imaging (MRI). Pelvic vBMD was calculated using whole-body dual-energy X-ray absorptiometry to measure pelvic bone mineral content and MRI-measured BV. An inverse correlation was found between pelvic BMAT and pelvic vBMD in both children (r=-0.374, pBMAT as the independent variable, being a child or adult neither significantly contribute to the pelvic BMD (p=0.995) nor did its interaction with pelvic BMAT (p=0.415). The inverse relationship observed between pelvic vBMD and pelvic BMAT in children extends previous findings that found the inverse relationship to exist in adults and provides further support for a reciprocal relationship between adipocytes and osteoblasts. Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Multiple measures of adiposity are associated with mean leukocyte telomere length in the northern Finland birth cohort 1966.

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Jessica L Buxton

Full Text Available Studies of leukocyte telomere length (LTL and adiposity have produced conflicting results, and the relationship between body mass index (BMI and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i childhood growth measures (BMI and age at adiposity rebound (AR; ii change in BMI from childhood to adulthood and iii adult BMI, waist-to-hip ratio (WHR, body adiposity index (BAI. Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041. Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively and women (P = 0.029 and P = 0.008, respectively, and BAI in women (P = 0.021 were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008. We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing.

Adipose Tissue-Derived Mesenchymal Stem Cells as a New Host Cell in Latent Leishmaniasis

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Allahverdiyev, Adil M.; Bagirova, Melahat; Elcicek, Serhat; Koc, Rabia Cakir; Baydar, Serap Yesilkir; Findikli, Necati; Oztel, Olga N.

2011-01-01

Some protozoan infections such as Toxoplasma, Cryptosporidium, and Plasmodium can be transmitted through stem cell transplantations. To our knowledge, so far, there is no study about transmission of Leishmania parasites in stem cell transplantation and interactions between parasites and stem cells in vitro. Therefore, the aim of this study was to investigate the interaction between different species of Leishmania parasites and adipose tissue-derived mesenchymal stem cells (ADMSCs). ADMSCs have been isolated, cultured, characterized, and infected with different species of Leishmania parasites (L. donovani, L. major, L. tropica, and L. infantum). Infectivity was examined by Giemsa staining, microculture, and polymerase chain reaction methods. As a result, infectivity of ADMSCs by Leishmania parasites has been determined for the first time in this study. According to our findings, it is very important that donors are screened for Leishmania parasites before stem cell transplantations in regions where leishmaniasis is endemic. PMID:21896818

Comparative Evaluation of Human Mesenchymal Stem Cells of Fetal (Wharton's Jelly and Adult (Adipose Tissue Origin during Prolonged In Vitro Expansion: Considerations for Cytotherapy

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I. Christodoulou

2013-01-01

Full Text Available Mesenchymal stem cells (MSCs are somatic cells with a dual capacity for self-renewal and differentiation, and diverse therapeutic applicability, both experimentally and in the clinic. These cells can be isolated from various human tissues that may differ anatomically or developmentally with relative ease. Heterogeneity due to biological origin or in vitro manipulation is, nevertheless, considerable and may equate to differences in qualitative and quantitative characteristics which can prove crucial for successful therapeutic use. With this in mind, in the present study we have evaluated the proliferation kinetics and phenotypic characteristics of MSCs derived from two abundant sources, that is, fetal umbilical cord matrix (Wharton's jelly and adult adipose tissue (termed WJSC and ADSC, resp. during prolonged in vitro expansion, a process necessary for obtaining cell numbers sufficient for clinical application. Our results show that WJSC are derived with relatively high efficiency and bear a substantially increased proliferation capacity whilst largely sustaining the expression of typical immunophenotypic markers, whereas ADSC exhibit a reduced proliferation potential showing typical signs of senescence at an early stage. By combining kinetic with phenotypic data we identify culture thresholds up to which both cell types maintain their stem properties, and we discuss the practical implications of their differences.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

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Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Bone Formation by Sheep Stem Cells in an Ectopic Mouse Model: Comparison of Adipose and Bone Marrow Derived Cells and Identification of Donor-Derived Bone by Antibody Staining

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Kristian Kjærgaard

2016-01-01

Full Text Available Background. Scaffolds for bone tissue engineering (BTE can be loaded with stem and progenitor cells (SPC from different sources to improve osteogenesis. SPC can be found in bone marrow, adipose tissue, and other tissues. Little is known about osteogenic potential of adipose-derived culture expanded, adherent cells (A-CEAC. This study compares in vivo osteogenic capacity between A-CEAC and bone marrow derived culture expanded, adherent cells (BM-CEAC. Method. A-CEAC and BM-CEAC were isolated from five female sheep and seeded on hydroxyapatite granules prior to subcutaneous implantation in immunodeficient mice. The doses of cells in the implants were 0.5 × 106, 1.0 × 106, or 1.5 × 106 A-CEAC and 0.5 × 106 BM-CEAC, respectively. After eight weeks, bone volume versus total tissue volume (BV/TV was quantified using histomorphometry. Origin of new bone was assessed using human vimentin (HVIM antibody staining. Results. BM-CEAC yielded significantly higher BV/TV than any A-CEAC group, and differences between A-CEAC groups were not statistically significant. HVIM antibody stain was successfully used to identify sheep cells in this model. Conclusion. A-CEAC and BM-CEAC were capable of forming bone, and BM-CEAC yielded significantly higher BV/TV than any A-CEAC group. In vitro treatment to enhance osteogenic capacity of A-CEAC is suggested for further research in ovine bone tissue engineering.

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection.

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Lake, Jordan E

2017-12-01

The aim of this review is to summarize knowledge of the prevalence, relevant physiology, and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions. Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist. Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

Chondrogenic Differentiation of Human Adipose-Derived Stem Cells: A New Path in Articular Cartilage Defect Management?

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Jan-Philipp Stromps

2014-01-01

Full Text Available According to data published by the Centers for Disease Control and Prevention, over 6 million people undergo a variety of medical procedures for the repair of articular cartilage defects in the U.S. each year. Trauma, tumor, and age-related degeneration can cause major defects in articular cartilage, which has a poor intrinsic capacity for healing. Therefore, there is substantial interest in the development of novel cartilage tissue engineering strategies to restore articular cartilage defects to a normal or prediseased state. Special attention has been paid to the expansion of chondrocytes, which produce and maintain the cartilaginous matrix in healthy cartilage. This review summarizes the current efforts to generate chondrocytes from adipose-derived stem cells (ASCs and provides an outlook on promising future strategies.

Whole-body adipose tissue and lean muscle volumes and their distribution across gender and age: MR-derived normative values in a normal-weight Swiss population.

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Ulbrich, Erika J; Nanz, Daniel; Leinhard, Olof Dahlqvist; Marcon, Magda; Fischer, Michael A

2018-01-01

To determine age- and gender-dependent whole-body adipose tissue and muscle volumes in healthy Swiss volunteers in Dixon MRI in comparison with anthropometric and bioelectrical impedance (BIA) measurements. Fat-water-separated whole-body 3 Tesla MRI of 80 healthy volunteers (ages 20 to 62 years) with a body mass index (BMI) of 17.5 to 26.2 kg/m 2 (10 men, 10 women per decade). Age and gender-dependent volumes of total adipose tissue (TAT), visceral adipose tissue (VAT), total abdominal subcutaneous adipose tissue (ASAT) and total abdominal adipose tissue (TAAT), and the total lean muscle tissue (TLMT) normalized for body height were determined by semi-automatic segmentation, and correlated with anthropometric and BIA measurements as well as lifestyle parameters. The TAT, ASAT, VAT, and TLMT indexes (TATi, ASATi, VATi, and TLMTi, respectively) (L/m 2  ± standard deviation) for women/men were 6.4 ± 1.8/5.3 ± 1.7, 1.6 ± 0.7/1.2 ± 0.5, 0.4 ± 0.2/0.8 ± 0.5, and 5.6 ± 0.6/7.1 ± 0.7, respectively. The TATi correlated strongly with ASATi (r > 0.93), VATi, BMI and BIA (r > 0.70), and TAATi (r > 0.96), and weak with TLMTi for both genders (r > -0.34). The VAT was the only parameter showing an age dependency (r > 0.32). The BMI and BIA showed strong correlation with all MR-derived adipose tissue volumes. The TAT mass was estimated significantly lower from BIA than from MRI (both genders P muscle volumes might serve as normative values. The estimation of adipose tissue volumes was significantly lower from anthropometric and BIA measurements than from MRI. Magn Reson Med 79:449-458, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2.

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Cui, Lei; Yin, Shuo; Liu, Wei; Li, Ningli; Zhang, Wenjie; Cao, Yilin

2007-06-01

Multipotent mesenchymal stem cells (MSCs) in adult tissue are known to be less immunogenic and immunosuppressive. Previous study showed that primary cultures of human adipose-derived stem cells (ADSCs) shared their immunomodulatory properties with other MSCs. However, whether passaged human ADSCs can retain their immunomodulatory effect after in vitro expansion remains unknown. In addition, the mechanism of ADSC-mediated immunomodulatory effect remains to be elucidated. This study aimed to investigate these issues by using passaged human ADSCs as an in vitro study model. Flow cytometry showed that passaged ADSCs expressed human leukocyte antigen (HLA) class I but not class II molecules, which could be induced to express to a high level with interferon-gamma (IFN-gamma) treatment. The study found that passaged ADSCs could not elicit lymphocyte proliferation after co-culturing with them, even after IFN-gamma treatment. In addition, either IFN-gamma-treated or non-treated ADSCs could inhibit phytohemagglutinin (PHA)-stimulated lymphocyte proliferation. Moreover, passaged ADSCs could serve as the third-party cells to inhibited two-way mixed lymphocyte reaction (MLR). Further study using a transwell system also showed that this type of immunosuppressive effect was not cell-cell contact dependent. In defining possible soluble factors, we found that passaged ADSCs significantly increased their secretion of prostaglandin E2 (PGE2), but not transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF), when they were co-cultured with MLR. Furthermore, the result demonstrated that only PGE2 production inhibitor indomethacine, but not TGF-beta- and HGF-neutralizing antibodies, could significantly counteract ADSC-mediated suppression on allogeneic lymphocyte proliferation. These results indicated that in vitro expanded ADSCs retain low immunogenicity and immunosuppressive effect, and PGE2 might be the major soluble factor involved in the in vitro inhibition of

Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue

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Hersoug, L-G.; Møller, Peter; Loft, Steffen

2016-01-01

The composition of the gut microbiota and excessive ingestion of high-fat diets (HFD) are considered to be important factors for development of obesity. In this review we describe a coherent mechanism of action for the development of obesity, which involves the composition of gut microbiota, HFD...... is involved in the development of obesity as a direct targeting molecule for lipid delivery and storage in adipose tissue....

In vitro generation of functional insulin-producing cells from lipoaspirated human adipose tissue-derived stem cells.

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Mohamad Buang, Mohamad Lizan; Seng, Heng Kien; Chung, Lee Han; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

2012-01-01

Tissue engineering strategy has been considered as an alternative treatment for diabetes mellitus due to lack of permanent pharmaceutical treatment and islet donors for transplantation. Various cell lines have been used to generate functional insulin-producing cells (IPCs) including progenitor pancreatic cell lines, embryonic stem cells (ESCs), umbilical cord blood stem cells (UCB-SCs), adult bone marrow stem cells (BMSCs), and adipose tissue-derived stem cells (ADSCs). Human ADSCs from lipoaspirated abdominal fat tissue was differentiated into IPCs following a two-step induction protocol based on a combination of alternating high and low glucose, nicotinamide, activin A and glucagon-like peptide 1 (GLP-1) for a duration of 3 weeks. During differentiation, histomorphological changes of the stem cells towards pancreatic β-islet characteristics were observed via light microscope and transmission electron microscope (TEM). Dithizone (DTZ) staining, which is selective towards IPCs, was used to stain the new islet-like cells. Production of insulin hormone by the cells was analyzed via enzyme-linked immunosorbent assay (ELISA), whereas its hormonal regulation was tested via a glucose challenge test. Histomorphological changes of the differentiated cells were noted to resemble pancreatic β-cells, whereas DTZ staining positively stained the cells. The differentiated cells significantly produced human insulin as compared to the undifferentiated ADSCs, and its production was increased with an increase of glucose concentration in the culture medium. These initial data indicate that human lipoaspirated ADSCs have the potential to differentiate into functional IPCs, and could be used as a therapy to treat diabetes mellitus in the future. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Human Breast Adipose-Derived Stem Cells Transfected with the Stromal Cell-Derived Factor-1 Receptor CXCR4 Exhibit Enhanced Viability in Human Autologous Free Fat Grafts

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Fang-tian Xu

2014-11-01

Full Text Available Background: The main complication of autologous free fat tissue transplantation is fat resorption and calcification due to the ischemic necrosis of fat. The promotion of transplant neovascularization soon after autologous free fat grafts may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1 and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4 are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. We hypothesized that CXCR4 may improve the long-term survival of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs and may therefore improve graft revascularization. In this study, we aimed to determine the effect of human breast adipose-derived stem cells (HBASCs transfected with the CXCR4 gene on the survival rate of human autologous free fat transplants in nude mice. Methods: Human breast adipose-derived stem cells (HBASCs were expanded ex vivo for 3 passages, labeled with green fluorescent protein (GFP and transfected with CXCR4 or left untransfected. Autologous fat tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A, GFP-labeled HBASCs (group B, the known vascularization-promoting agent VEGF (group C, or medium (group D and then injected subcutaneously into 32 nude mice at 4 spots in a random fashion. Six months later, the transplanted tissue volume and histology were evaluated, and neo-vascularization was quantified by counting the capillaries. CXCR4 and SDF-1α mRNA expression in the transplants was determined using real-time quantitative PCR analysis (qPCR. Results: The data revealed that the control (group D transplant volume survival was 28.3 ± 4.5%. Mixing CXCR4-transfected (group A and untransfected (group B HBASCs significantly increased transplant volume survival (79.5 ± 8.3% and 67.2 ± 5.9%, respectively, whereas VEGF-transfected HBASCs (group C were less effective (41.2 ± 5.1%. Histological

Characterization of Chondrogenic Gene Expression and Cartilage Phenotype Differentiation in Human Breast Adipose-Derived Stem Cells Promoted by Ginsenoside Rg1 In Vitro

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Fang-Tian Xu

2015-11-01

Full Text Available Background/Aims: Investigating and understanding chondrogenic gene expression during the differentiation of human breast adipose-derived stem cells (HBASCs into chondrogenic cells is a prerequisite for the application of this approach for cartilage repair and regeneration. In this study, we aim to characterize HBASCs and to examine chondrogenic gene expression in chondrogenic inductive culture medium containing ginsenoside Rg1. Methods: Human breast adipose-derived stem cells at passage 3 were evaluated based on specific cell markers and their multilineage differentiation capacity. Cultured HBASCs were treated either with basic chondrogenic inductive conditioned medium alone (group A, control or with basic chondrogenic inductive medium plus 10 µg/ml (group B, 50 µg/ml (group C, or 100µg/ml ginsenoside Rg1 (group D. Cell proliferation was assessed using the CCK-8 assay for a period of 9 days. Two weeks after induction, the expression of chondrogenic genes (collagen type II, collagen type XI, ACP, COMP and ELASTIN was determined using real-time PCR in all groups. Results: The different concentrations of ginsenoside Rg1 that were added to the basic chondrogenic inductive culture medium promoted the proliferation of HBASCs at earlier stages (groups B, C, and D but resulted in chondrogenic phenotype differentiation and higher mRNA expression of collagen type II (CO-II, collagen type XI (CO-XI, acid phosphatase (ACP, cartilage oligomeric matrix protein (COMP and ELASTIN compared with the control (group A at later stages. The results reveal an obvious positive dose-effect relationship between ginsenoside Rg1 and the proliferation and chondrogenic phenotype differentiation of HBASCs in vitro. Conclusions: Human breast adipose-derived stem cells retain stem cell characteristics after expansion in culture through passage 3 and serve as a feasible source of cells for cartilage regeneration in vitro. Chondrogenesis in HBASCs was found to be prominent

Maternal nutritional manipulations program adipose tissue dysfunction in offspring

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Simon eLecoutre

2015-05-01

Full Text Available Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates. Maternal nutritional manipulations reprogram offspring’s adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

SDF-1 improves wound healing ability of glucocorticoid-treated adipose tissue-derived mesenchymal stem cells.

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Kato, Toshiki; Khanh, Vuong Cat; Sato, Kazutoshi; Takeuchi, Kosuke; Carolina, Erica; Yamashita, Toshiharu; Sugaya, Hisashi; Yoshioka, Tomokazu; Mishima, Hajime; Ohneda, Osamu

2017-11-18

Glucocorticoids cause the delayed wound healing by suppressing inflammation that is required for wound healing process. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) play an important role for wound healing by their cytokine productions including stromal derived factor 1 (SDF-1). However, it has not been clear how glucocorticoids affect the wound healing ability of AT-MSCs. In this study, we found that glucocorticoid downregulated SDF-1 expression in AT-MSCs. In addition, glucocorticoid-treated AT-MSCs induced less migration of inflammatory cells and impaired wound healing capacity compared with glucocorticoid-untreated AT-MSCs. Of note, prostaglandin E2 (PGE2) synthesis-related gene expression was downregulated by glucocorticoid and PGE2 treatment rescued not only SDF-1 expression in the presence of glucocorticoid but also their wound healing capacity in vivo. Furthermore, we found SDF-1-overexpressed AT-MSCs restored wound healing capacity even after treatment of glucocorticoid. Consistent with the results obtained from glucocorticoid-treated AT-MSCs, we found that AT-MSCs isolated from steroidal osteonecrosis donors (sAT-MSCs) who received chronic glucocorticoid therapy showed less SDF-1 expression and impaired wound healing capacity compared with traumatic osteonecrosis donor-derived AT-MSCs (nAT-MSCs). Moreover, the SDF-1 level was also reduced in plasma derived from steroidal osteonecrosis donors compared with traumatic osteonecrosis donors. These results provide the evidence that concomitant application of AT-MSCs with glucocorticoid shows impaired biological modulatory effects that induce impaired wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

Proliferative and phenotypical characteristics of human adipose tissue-derived stem cells: comparison of Ficoll gradient centrifugation and red blood cell lysis buffer treatment purification methods.

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Najar, Mehdi; Rodrigues, Robim M; Buyl, Karolien; Branson, Steven; Vanhaecke, Tamara; Lagneaux, Laurence; Rogiers, Vera; De Kock, Joery

2014-09-01

Adult human subcutaneous adipose tissue harbors a multipotent stem cell population, the so-called human adipose tissue-derived mesenchymal stromal cells (AT-MSCs). These cells are able to differentiate in vitro into various cell types and possess immunomodulatory features. Yet procedures to obtain AT-MSCs can vary significantly. The two most extensively used AT-MSC purification techniques are (i) density gradient centrifugation using Ficoll and (ii) red blood cell (RBC) lysis buffer treatment of the stromal vascular fraction. In the context of potential clinical cell therapy, the stem cell yield after purification and upon consecutive passages, as well as the purity of the obtained cell population, are of utmost importance. We investigated the expansion capacity and purity of AT-MSCs purified by both procedures immediately after isolation and upon consecutive passages. We also investigated possible purification-dependent differences in their expression of immune-inhibitory factors and cell adhesion molecules. We found that RBC lysis buffer treatment is a more robust and easier method to purify AT-MSCs than density gradient fractionation. However, the resulting AT-MSC-RBC population contains a significantly higher number of CD34(+) cells, particularly during the first passages after plating. From passage 4 onward, no significant differences could be observed between both populations with respect to the immunophenotype, expansion capacity and expression of immune inhibitory factors and cell adhesion molecules. Our data show that RBC lysis buffer treatment may be a good alternative to density fractionation, providing a faster, more robust and easier method to purify AT-MSCs with biologically preserved characteristics. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Socio-demographic, lifestyle, and dietary determinants of essential and possibly-essential trace element levels in adipose tissue from an adult cohort.

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Rodríguez-Pérez, Celia; Vrhovnik, Petra; González-Alzaga, Beatriz; Fernández, Mariana F; Martin-Olmedo, Piedad; Olea, Nicolás; Fiket, Željka; Kniewald, Goran; Arrebola, Juan P

2018-05-01

There is increasing evidence linking levels of trace elements (TEs) in adipose tissue with certain chronic conditions (e.g., diabetes or obesity). The objectives of this study were to assess concentrations of a selection of nine essential and possibly-essential TEs in adipose tissue samples from an adult cohort and to explore their socio-demographic, dietary, and lifestyle determinants. Adipose tissue samples were intraoperatively collected from 226 volunteers recruited in two public hospitals from Granada province. Trace elements (Co, Cr, Cu, Fe, Mn, Mo, Se, V, and Zn) were analyzed in adipose tissue by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Data were collected on socio-demographic characteristics, lifestyle, diet, and health status by face-to-face interview. Predictors of TE concentrations were assessed by using multivariable linear and logistic regression. All TEs were detected in all samples with the exception of Se (53.50%). Iron, zinc, and copper showed the highest concentrations (42.60 mg/kg, 9.80 mg/kg, and 0.68 mg/kg, respectively). Diet was the main predictor of Cr, Fe, Mo, and Se concentrations. Body mass index was negatively associated with all TEs (β coefficients = -0.018 to -0.593, p = 0.001-0.090) except for Mn and V. Age showed a borderline-significant positive correlation with Cu (β = 0.004, p = 0.089). Residence in a rural or semi-rural area was associated with increased Co, Cr, Fe, Mo, Mn, V and Zn concentrations and with β coefficients ranging from 0.196 to 0.544 (p V concentrations (β coefficients = 0.276-0.368, p = 0.022-0.071). This is the first report on the distribution of these TEs in adipose tissue and on their determinants in a human cohort and might serve as an initial step in the elucidation of their clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions : A pilot study

NARCIS (Netherlands)

Geburek, Florian; Mundle, Kathrin; Conrad, Sabine; Hellige, Maren; Walliser, Ulrich; van Schie, Hans T M; van Weeren, René; Skutella, Thomas; Stadler, Peter M

2016-01-01

BACKGROUND: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of

Field metabolic rate and PCB adipose tissue deposition efficiency in East Greenland polar bears derived from contaminant monitoring data.

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Pavlova, Viola; Nabe-Nielsen, Jacob; Dietz, Rune; Svenning, Jens-Christian; Vorkamp, Katrin; Rigét, Frank Farsø; Sonne, Christian; Letcher, Robert J; Grimm, Volker

2014-01-01

Climate change will increasingly affect the natural habitat and diet of polar bears (Ursus maritimus). Understanding the energetic needs of polar bears is therefore important. We developed a theoretical method for estimating polar bear food consumption based on using the highly recalcitrant polychlorinated biphenyl (PCB) congener, 2,2',4,4',55-hexaCB (CB153) in bear adipose tissue as an indicator of food intake. By comparing the CB153 tissue concentrations in wild polar bears with estimates from a purposely designed individual-based model, we identified the possible combinations of field metabolic rates (FMR) and CB153 deposition efficiencies in East Greenland polar bears. Our simulations indicate that if 30% of the CB153 consumed by polar bear individuals were deposited into their adipose tissue, the corresponding FMR would be only two times the basal metabolic rate. In contrast, if the modelled CB153 deposition efficiency were 10%, adult polar bears would require six times more energy than that needed to cover basal metabolism. This is considerably higher than what has been assumed for polar bears in previous studies though it is similar to FMRs found in other marine mammals. An implication of this result is that even relatively small reductions in future feeding opportunities could impact the survival of East Greenland polar bears.

Ethical, legal and practical issues of establishing an adipose stem cell bank for research.

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West, C C; Murray, I R; González, Z N; Hindle, P; Hay, D C; Stewart, K J; Péault, B

2014-06-01

Access to human tissue is critical to medical research, however the laws and regulations surrounding gaining ethical and legal access to tissue are often poorly understood. Recently, there has been a huge increase in the interest surrounding the therapeutic application of adipose tissue, and adipose-derived stem cells. To facilitate our own research interests and possibly assist our local colleagues and collaborators, we established a Research Tissue Bank (RTB) to collect, store and distribute human adipose tissue derived cells with all the appropriate ethical approval for subsequent downstream research. Here we examine the legal, ethical and practical issues relating to the banking of adipose tissue for research in the UK, and discuss relevant international guidelines and policies. We also share our experiences of establishing an RTB including the necessary infrastructure and the submission of an application to a Research Ethics Committee (REC). Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation and polarization in type 2 diabetic ApoE-/- mouse.

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Liu, Ming-Hao; Li, Ya; Han, Lu; Zhang, Yao-Yuan; Wang, Di; Wang, Zhi-Hao; Zhou, Hui-Min; Song, Ming; Li, Yi-Hui; Tang, Meng-Xiong; Zhang, Wei; Zhong, Ming

2017-07-01

Atherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4 + T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4 + T cells as well. Whether T2DM ADSCs are impaired in antagonizing CD4 + T cell proliferation and polarization remains unclear. We constructed type 2 diabetic ApoE -/- mouse models and tested infiltration and subgroups of CD4 + T cell in stromal-vascular fraction (SVF) in vivo. Normal/T2DM ADSCs and normal splenocytes with or without CD4 sorting were separated and co-cultured at different scales ex vivo. Immune phenotypes of pro- and anti-inflammation of ADSCs were also investigated. Flow cytometry (FCM) and ELISA were applied in the experiments above. CD4 + T cells performed a more pro-inflammatory phenotype in adipose tissue in T2DM ApoE -/- mice in vivo. Restriction to CD4 + T cell proliferation and polarization was manifested obviously weakened after co-cultured with T2DM ADSCs ex vivo. No obvious distinctions were found in morphology and growth type of both ADSCs. However, T2DM ADSCs acquired a pro-inflammatory immune phenotype, with secreting less PGE2 and expressing higher MHC-II and co-stimulatory molecules (CD40, CD80). Normal ADSCs could also obtain the phenotypic change after cultured with T2DM SVF supernatant. CD4 + T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabetic ApoE -/- mice. T2DM ADSCs had impaired function in restricting CD4 + T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cesarean Section Is Associated with Increased Peripheral and Central Adiposity in Young Adulthood: Cohort Study.

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Denise N Mesquita

Full Text Available Cesarean section (CS has been associated with obesity, measured by body mass index (BMI, in some studies. It has been hypothesized that this association, if causal, might be explained by changes in gut microbiota. However, little is known about whether CS is also associated with increased adiposity as measured by indicators other than BMI.To assess the association between CS and indicators of peripheral and central adiposity in young adults.The study was conducted on 2,063 young adults aged 23 to 25 years from the 1978/79Ribeirão Preto birth cohort, São Paulo, Brazil. CS was the independent variable. The anthropometric indicators of adiposity were: waist circumference (WC, waist-height ratio (WHtR, waist-hip ratio (WHR, tricipital skinfold (TSF, and subscapular skinfold (SSF. The association between CS and indicators of adiposity was investigated using a Poisson model, with robust adjustment of variance and calculation of incidence rate ratio (IRR with 95% confidence interval (95%CI, and adjustment for birth variables.Follow-up rate was 31.8%. The CS rate was 32%. Prevalences of increased WC, WHtR, WHR were 32.1%, 33.0% and 15.2%, respectively. After adjustment for birth variables, CS was associated with increased risk of adiposity when compared to vaginal delivery: 1.22 (95%CI 1.07; 1.39 for WC, 1.25 (95%CI 1.10;1.42 for WHtR, 1.45 (95%CI 1.18;1.79 for WHR, 1.36 (95%CI 1.04;1.78 for TSF, and 1.43 (95%CI 1.08;1.91 for SSF.Subjects born by CS had a higher risk for increased peripheral and central adiposity during young adult age compared to those born by vaginal delivery. The association of CS with adiposity was consistently observed for all indicators and was robust after adjustment for a variety of early life confounders.

A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

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Han Jin Cho

2015-04-01

Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older Adults

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Shen, Wei; Chen, Jun; Gantz, Madeleine; Punyanitya, Mark; Heymsfield, Steven B; Gallagher, Dympna; Albu, Jeanine; Engelson, Ellen; Kotler, Donald; Pi-Sunyer, Xavier; Gilsanz, Vicente

2012-01-01

Background/Objective Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM) (age 18.0-39.9 yrs) and an older group with potential bone loss (PoBL) (age 40.0-88 yrs). S...

Correlation of adiposity indices with cardiovascular disease risk factors in healthy adults of Singapore: a cross-sectional study

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Bi, Xinyan; Tey, Siew Ling; Leong, Claudia; Quek, Rina; Loo, Yi Ting; Henry, Christiani Jeyakumar

2016-01-01

Background Obesity has long been highlighted for its association with increased incidence of cardiovascular disease (CVD). Nonetheless, the best adiposity indices to evaluate the CVD risk factors remain contentious and few studies have been performed in Asian populations. In the present study, we compared the association strength of percent body fat (PBF) to indirect anthropometric measures of general adiposity (body mass index (BMI) and body adiposity index (BAI)) and central adiposity (wais...

Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

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Ding, Xian-Fei; Sun, Mou; Guan, Fang-Xia; Guo, Li-Na; Zhang, Yan-Yan; Wan, You-Dong; Zhang, Xiao-Juan; Yu, Yan-Wu; Ma, Shan-Shan; Yao, Hai-Mu; Yao, Rui; Zhang, Rui-Fang; Sun, Tong-Wen; Kan, Quan-Cheng

2017-11-06

Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Enrichment of Adipose-Derived Stromal Cells for BMPR1A Facilitates Enhanced Adipogenesis.

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Zielins, Elizabeth R; Paik, Kevin; Ransom, Ryan C; Brett, Elizabeth A; Blackshear, Charles P; Luan, Anna; Walmsley, Graham G; Atashroo, David A; Senarath-Yapa, Kshemendra; Momeni, Arash; Rennert, Robert; Sorkin, Michael; Seo, Eun Young; Chan, Charles K; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

2016-02-01

Reconstruction of soft tissue defects has traditionally relied on the use of grafts and flaps, which may be associated with variable resorption and/or significant donor site morbidity. Cell-based strategies employing adipose-derived stromal cells (ASCs), found within the stromal vascular fraction (SVF) of adipose tissue, may offer an alternative strategy for soft tissue reconstruction. In this study, we investigated the potential of a bone morphogenetic protein receptor type 1A (BMPR1A)(+) subpopulation of ASCs to enhance de novo adipogenesis. Human lipoaspirate was enzymatically digested to isolate SVF and magnetic-activated cell separation was utilized to obtain BMPR1A(+) and BMPR1A(-) cells. These cells, along with unenriched cells, were expanded in culture and evaluated for adipogenic gene expression and in vitro adipocyte formation. Cells from each group were also labeled with a green fluorescent protein (GFP) lentivirus and transplanted into the inguinal fat pads, an adipogenic niche, of immunocompromised mice to determine their potential for de novo adipogenesis. Confocal microscopy along with staining of lipid droplets and vasculature was performed to evaluate the formation of mature adipocytes by transplanted cells. In comparison to BMPR1A(-) and unenriched ASCs, BMPR1A(+) cells demonstrated significantly enhanced adipogenesis when cultured in an adipogenic differentiation medium, as evidenced by increased staining with Oil Red O and increased expression of peroxisome proliferator-activating receptor gamma (PPAR-γ) and fatty acid-binding protein 4 (FABP4). BMPR1A(+) cells also formed significantly more adipocytes in vivo, as demonstrated by quantification of GFP+ adipocytes. Minimal formation of mature adipocytes was appreciated by BMPR1A(-) cells. BMPR1A(+) ASCs show an enhanced ability for adipogenesis in vitro, as shown by gene expression and histological staining. Furthermore, within an adipogenic niche, BMPR1A(+) cells possessed an increased capacity

Moderate hypoxia influences potassium outward currents in adipose-derived stem cells.

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Mayuri Prasad

Full Text Available Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+ channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current-voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels.

Influence of smartphone Wi-Fi signals on adipose-derived stem cells.

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Lee, Sang-Soon; Kim, Hyung-Rok; Kim, Min-Sook; Park, Sanghoon; Yoon, Eul-Sik; Park, Seung-Ha; Kim, Deok-Woo

2014-09-01

The use of smartphones is expanding rapidly around the world, thus raising the concern of possible harmful effects of radiofrequency generated by smartphones. We hypothesized that Wi-Fi signals from smartphones may have harmful influence on adipose-derived stem cells (ASCs). An in vitro study was performed to assess the influence of Wi-Fi signals from smartphones. The ASCs were incubated under a smartphone connected to a Wi-Fi network, which was uploading files at a speed of 4.8 Mbps for 10 hours a day, for a total of 5 days. We constructed 2 kinds of control cells, one grown in 37°C and the other grown in 39°C. After 5 days of Wi-Fi exposure from the smartphone, the cells underwent cell proliferation assay, apoptosis assay, and flow cytometry analysis. Three growth factors, vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor-β, were measured from ASC-conditioned media. Cell proliferation rate was higher in Wi-Fi-exposed cells and 39°C control cells compared with 37°C control cells. Apoptosis assay, flow cytometry analysis, and growth factor concentrations showed no remarkable differences among the 3 groups. We could not find any harmful effects of Wi-Fi electromagnetic signals from smartphones. The increased proliferation of ASCs under the smartphone, however, might be attributable to the thermal effect.

Evidence for the ectopic synthesis of melanin in human adipose tissue.

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Randhawa, Manpreet; Huff, Tom; Valencia, Julio C; Younossi, Zobair; Chandhoke, Vikas; Hearing, Vincent J; Baranova, Ancha

2009-03-01

Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes. In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using real-time polymerase chain reaction and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with liquid chromatography/ultraviolet/mass spectrometry determination of the pyrrole-2,3,5-tricarboxylic acid (PTCA) derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U-(14)C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted. We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that uses its anti-inflammatory and its oxidative damage-absorbing properties. In conclusion, our study demonstrates for the first time that the melanin biosynthesis pathway is functional in adipose tissue.

Definition of new cut-offs of BMI and waist circumference based on body composition and insulin resistance: differences between children, adolescents and adults.

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Hübers, M; Pourhassan, M; Braun, W; Geisler, C; Müller, M J

2017-09-01

This study aims to determine associations between anthropometric traits, regional fat depots and insulin resistance in children, adolescents and adults to define new cut-offs of body mass index (BMI) or waist circumference (WC). Cross-sectional data were assessed in 433 children, adolescents and adults (aged: 6-60 years, BMI: 23.6 [21.0-27.7] kg m -2 ). Total adipose tissue (TAT), regional subcutaneous adipose tissue (SAT total , SAT trunk ) and visceral adipose tissue (VAT) were determined by whole-body magnetic resonance imaging, fat mass by air-displacement plethysmography. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Bivariate as well as partial correlations and regression analyses were used. Cut-off values of BMI and WC related to regional fat depots and HOMA-IR were analysed by receiver operating characteristics curve. In adults, TAT, SAT total and SAT trunk increased linearly with increasing BMI and WC, whereas they followed a cubic function in children and adolescents with a steep increase at BMI and WC ≥1 standard deviation score and VAT at WC ≥2 standard deviation score. Sex differences were apparent in adults with women having higher masses of TAT and SAT and men having higher VAT. Using established BMI or WC cut-offs, correspondent masses of TAT, SAT total , SAT trunk and VAT increased from childhood to adulthood. In all age groups, there were positive associations between BMI, WC, SAT trunk , VAT and HOMA-IR. When compared with normative cut-offs of BMI or WC, HOMA-IR-derived cut-offs of regional fat depots were lower in all age groups. Associations between BMI, WC and regional fat depots varied between children, adolescents, young and older adults. When compared with BMI-derived and WC-derived values, an insulin resistance-derived cut-off corresponded to lower masses of regional fat depots. Thus, established BMI and WC cut-offs are not appropriate to assess metabolic disturbances associated

Characterization of a PLGA sandwiched cell/fibrin tubular construct and induction of the adipose derived stem cells into smooth muscle cells

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Wang Xiaohong; Maekitie, Antti A.; Paloheimo, Kaija-Stiina; Tuomi, Jukka; Paloheimo, Markku; Sui Shaochun; Zhang Qiqing

2011-01-01

A poly(DL-lactic-co-glycolic acid) (PLGA) sandwiched adipose derived stem cell (ADSC)/fibrin tubular construct, fabricated using a step-by-step mold/extraction method, was characterized in this work. The ADSCs were also induced into smooth-muscle-like cells using growth factors such as hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB), transforming growth factor β1 (TGFβ1), and basic fibroblast growth factor (b-FGF). Compared with the non-induced cells, the proliferation ability of induced cells was much smaller. The PLGA sandwiched cell/hydrogel construct was shown to be useful for controlling the cellular microenvironment and cellular behaviors such as growth, migration, proliferation and differentiation. This strategy seems promising in tissue engineering and organ manufacturing.

Characterization of a PLGA sandwiched cell/fibrin tubular construct and induction of the adipose derived stem cells into smooth muscle cells

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Wang Xiaohong, E-mail: wangxiaohong@tsinghua.edu.cn [BIT Research Centre, School of Science and Technology, Aalto University, P.O. Box 15500, 00076 Aalto (Finland); Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Maekitie, Antti A.; Paloheimo, Kaija-Stiina; Tuomi, Jukka; Paloheimo, Markku [BIT Research Centre, School of Science and Technology, Aalto University, P.O. Box 15500, 00076 Aalto (Finland); Sui Shaochun [Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Zhang Qiqing [Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192 (China)

2011-05-10

A poly(DL-lactic-co-glycolic acid) (PLGA) sandwiched adipose derived stem cell (ADSC)/fibrin tubular construct, fabricated using a step-by-step mold/extraction method, was characterized in this work. The ADSCs were also induced into smooth-muscle-like cells using growth factors such as hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB), transforming growth factor {beta}1 (TGF{beta}1), and basic fibroblast growth factor (b-FGF). Compared with the non-induced cells, the proliferation ability of induced cells was much smaller. The PLGA sandwiched cell/hydrogel construct was shown to be useful for controlling the cellular microenvironment and cellular behaviors such as growth, migration, proliferation and differentiation. This strategy seems promising in tissue engineering and organ manufacturing.

Association of Adiposity Indices with Platelet Distribution Width and Mean Platelet Volume in Chinese Adults.

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Jian Hou

Full Text Available Hypoxia is a prominent characteristic of inflammatory tissue lesions. It can affect platelet function. While mean platelet volume (MPV and platelet distribution width (PDW are sample platelet indices, they may reflect subcinical platelet activation. To investigated associations between adiposity indices and platelet indices, 17327 eligible individuals (7677 males and 9650 females from the Dongfeng-Tongji Cohort Study (DFTJ-Cohort Study, n=27009 were included in this study, except for 9682 individuals with missing data on demographical, lifestyle, physical indicators and diseases relative to PDW and MPV. Associations between adiposity indices including waist circumstance (WC, waist-to-height ratio (WHtR, body mass index (BMI, and MPV or PDW in the participants were analyzed using multiple logistic regressions. There were significantly negative associations between abnormal PDW and WC or WHtR for both sexes (ptrend<0.001 for all, as well as abnormal MPV and WC or WHtR among female participants (ptrend<0.05 for all. In the highest BMI groups, only females with low MPV or PDW were at greater risk for having low MPV (OR=1.33, 95% CI=1.10, 1.62 ptrend<0.001 or PDW (OR=1.34, 95% CI=1.14, 1.58, ptrend<0.001 than those who had low MPV or PDW in the corresponding lowest BMI group. The change of PDW seems more sensitive than MPV to oxidative stress and hypoxia. Associations between reduced PDW and MPV values and WC, WHtR and BMI values in Chinese female adults may help us to further investigate early changes in human body.

Adiposity to muscle ratio predicts incident physical limitation in a cohort of 3,153 older adults--an alternative measurement of sarcopenia and sarcopenic obesity.

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Auyeung, Tung Wai; Lee, Jenny Shun Wah; Leung, Jason; Kwok, Timothy; Woo, Jean

2013-08-01

Conventionally, sarcopenia is defined by muscle mass and physical performance. We hypothesized that the disability caused by sarcopenia and sarcopenic obesity was related to the amount of adiposity or body weight bearing on a unit of muscle mass, or the adiposity to muscle ratio. We therefore examined whether this ratio could predict physical limitation by secondary analysis of the data in our previous study. We recruited 3,153 community-dwelling adults aged >65 years and their body composition was measured by dual-energy X-ray absorptiometry. Assessment of physical limitation was undertaken 4 years later. The relationship between baseline adiposity to muscle ratio and incident physical limitation was examined by logistic regression. In men, the adiposity to muscle ratios, namely total body fat to lower-limb muscle mass, total body fat to fat-free mass (FFM), and body weight to FFM, were predictive of physical limitation before and after adjustment for the covariates: age, Mini-mental Status Examination score, Geriatric Depression Scale score >8, and the diagnosis of chronic obstructive pulmonary disease, diabetes mellitus, hypertension, heart disease, and stroke (all p values physical limitation 4 years later both before and after adjustment for the same set of covariates (all p values physical limitation in older women across the entire range of the total body fat to lower-limb muscle mass ratio; and in older men when this ratio was equal to or greater than 0.75.

Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

DEFF Research Database (Denmark)

Ahlqvist, Emma; Osmark, Peter; Kuulasmaa, Tiina

2013-01-01

Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis...... and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher...... for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue...

Overexpressed human heme Oxygenase-1 decreases adipogenesis in pigs and porcine adipose-derived stem cells.

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Park, Eun Jung; Koo, Ok Jae; Lee, Byeong Chun

2015-11-27

Adipose-derived mesenchymal stem cells (ADSC) are multipotent, which means they are able to differentiate into several lineages in vivo and in vitro under proper conditions. This indicates it is possible to determine the direction of differentiation of ADSC by controlling the microenvironment. Heme oxygenase 1 (HO-1), a type of antioxidant enzyme, attenuates adipogenicity and obesity. We produced transgenic pigs overexpressing human HO-1 (hHO-1-Tg), and found that these animals have little fatty tissue when autopsied. To determine whether overexpressed human HO-1 suppresses adipogenesis in pigs, we analyzed body weight increases of hHO-1-Tg pigs and wild type (WT) pigs of the same strain, and induced adipogenic differentiation of ADSC derived from WT and hHO-1-Tg pigs. The hHO-1-Tg pigs had lower body weights than WT pigs from 16 weeks of age until they died. In addition, hHO-1-Tg ADSC showed reduced adipogenic differentiation and expression of adipogenic molecular markers such as PPARγ and C/EBPα compared to WT ADSC. These results suggest that HO-1 overexpression reduces adipogenesis both in vivo and in vitro, which could support identification of therapeutic targets of obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells.

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Kostyuk, Svetlana; Smirnova, Tatiana; Kameneva, Larisa; Porokhovnik, Lev; Speranskij, Anatolij; Ershova, Elizaveta; Stukalov, Sergey; Izevskaya, Vera; Veiko, Natalia

2015-01-01

Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA. Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA) and results in both single- and double-strand DNA breaks (comet assay and γH2AX, foci). As a result in the cells significantly increases the expression of repair genes (BRCA1 (RT-PCR), PCNA (FACS)) and antiapoptotic genes (BCL2 (RT-PCR and FACS), BCL2A1, BCL2L1, BIRC3, and BIRC2 (RT-PCR)). Under the action of GC-DNA the potential of mitochondria was increased. Here we show that GC-rich extracellular DNA stimulates adipocyte differentiation of human adipose-derived mesenchymal stem cells (haMSCs). Exposure to GC-DNA leads to an increase in the level of RNAPPARG2 and LPL (RT-PCR), in the level of fatty acid binding protein FABP4 (FACS analysis) and in the level of fat (Oil Red O). GC-rich fragments in the pool of cfDNA can potentially induce oxidative stress and DNA damage response and affect the direction of mesenchymal stem cells differentiation in human adipose-derived mesenchymal stem cells. Such a response may be one of the causes of obesity or osteoporosis.

Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.

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Schendel, Stephen A

2017-10-01

Autologous collagen is an ideal soft tissue filler and may serve as a matrix for stem cell implantation and growth. Procurement of autologous collagen has been limited, though, secondary to a sufficient source. Liposuction is a widely performed and could be a source of autologous collagen. The amount of collagen and its composition in liposuctioned fat remains unknown. The purpose of this research was to characterize an adipose-derived tissue-based product created using ultrasonic cavitation and cryo-grinding. This study evaluated the cellular and protein composition of the final product. Fat was obtained from individuals undergoing routine liposuction and was processed by a 2 step process to obtain only the connective tissue. The tissue was then evaluated by scanning electronic microscope, Western blot analysis, and flow cytometry. Liposuctioned fat was obtained from 10 individuals with an average of 298 mL per subject. After processing an average of 1 mL of collagen matrix was obtained from each 100 mL of fat. Significant viable cell markers were present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ > CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other proteins. Scanning electronic microscope study showed a regular pattern of cross-linked, helical collagen. Additionally, vital staing demonstrated that the cells were still viable after processing. Collagen and cells can be easily obtained from liposuctioned fat by ultrasonic separation without alteration of the overall cellular composition of the tissue. Implantation results in new collagen and cellular growth. Collagen matrix with viable cells for autologous use can be obtained from liposuctioned fat and may provide long term results. 5. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Xenotransplantation of human adipose-derived stem cells in zebrafish embryos.

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Jin Li

Full Text Available Zebrafish is a widely used animal model with well-characterized background in developmental biology. The fate of human adipose-derived stem cells (ADSCs after their xenotransplantation into the developing embryos of zebrafish is unknown. Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral vector system carrying a green fluorescent protein (GFP reporter gene, and followed by detection of their cell viability and the expression of cell surface antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish embryos at 3.3-4.3 hour post-fertilization (hpf. Green fluorescent signal, the proliferation and differentiation of human ADSCs in recipient embryos were respectively examined using fluorescent microscopy and immunohistochemical staining. The results indicated that human ADSCs did not change their cell viability and the expression levels of cell surface antigens after GFP transduction. Microscopic examination demonstrated that green fluorescent signals of GFP expressed in the transplanted cells were observed in the embryos and larva fish at post-transplantation. The positive staining of Ki-67 revealed the survival and proliferation of human ADSCs in fish larvae after transplantation. The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31 expression was undetectable. Therefore, our results indicate that human ADSCs xenotransplanted in the zebrafish embryos not only can survive and proliferate at across-species circumstance, but also seem to maintain their undifferentiation status in a short term. This xenograft model of zebrafish embryos may provide a promising and useful technical platform for the investigation of biology and physiology of stem cells in vivo.

Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue.

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Yu, Xiao; Tang, Yuhan; Liu, Peiyi; Xiao, Lin; Liu, Liegang; Shen, Ruiling; Deng, Qianchun; Yao, Ping

2017-11-08

Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.

Human adipose-derived stromal cells in a clinically applicable injectable alginate hydrogel

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Larsen, Bjarke Follin; Juhl, Morten; Cohen, Smadar

2015-01-01

BACKGROUND AIMS: Clinical trials have documented beneficial effects of mesenchymal stromal cells from bone marrow and adipose tissue (ASCs) as treatment in patients with ischemic heart disease. However, retention of transplanted cells is poor. One potential way to increase cell retention is to in...

Enhanced mitogenesis in stromal vascular cells derived from subcutaneous adipose tissue of Wagyu compared with those of Angus cattle.

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Wei, S; Fu, X; Liang, X; Zhu, M J; Jiang, Z; Parish, S M; Dodson, M V; Zan, L; Du, M

2015-03-01

cells was lower than that of Angus, providing potential clues for breed differences on proliferation of SV cells in these two cattle breeds. The results of this study suggest that subcutaneous adipose-derived SV cells of Wagyu possess a lower trend of adipogenesis but higher mitogenesis compared with those of Angus.

Progranulin, a major secreted protein of mouse adipose-derived stem cells, inhibits light-induced retinal degeneration.

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Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tomohiro; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru; Hara, Hideaki

2014-01-01

Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina.

Induced pluripotent stem cells generated from human adipose-derived stem cells using a non-viral polycistronic plasmid in feeder-free conditions.

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Xinjian Qu

Full Text Available Induced pluripotent stem cells (iPSCs can be generated from somatic cells by ectopic expression of defined transcription factors (TFs. However, the optimal cell type and the easy reprogramming approaches that minimize genetic aberrations of parent cells must be considered before generating the iPSCs. This paper reports a method to generate iPSCs from adult human adipose-derived stem cells (hADSCs without the use of a feeder layer, by ectopic expression of the defined transcription factors OCT4, SOX2, KLF4 and C-MYC using a polycistronic plasmid. The results, based on the expression of pluripotent marker, demonstrated that the iPSCs have the characteristics similar to those of embryonic stem cells (ESCs. The iPSCs differentiated into three embryonic germ layers both in vitro by embryoid body generation and in vivo by teratoma formation after being injected into immunodeficient mice. More importantly, the plasmid DNA does not integrate into the genome of human iPSCs as revealed by Southern blotting experiments. Karyotypic analysis also demonstrated that the reprogramming of hADSCs by the defined factors did not induce chromosomal abnormalities. Therefore, this technology provides a platform for studying the biology of iPSCs without viral vectors, and can hopefully overcome immune rejection and ethical concerns, which are the two important barriers of ESC applications.

Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

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Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

2016-08-01

Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

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Park, Ye Seul; Uddin, Md Jamal; Piao, Lingjuan; Hwang, Inah; Lee, Jung Hwa; Ha, Hunjoo

2016-01-01

Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

The osteogenic differentiation of SSEA-4 sub-population of human adipose derived stem cells using silicate nanoplatelets.

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Mihaila, Silvia M; Gaharwar, Akhilesh K; Reis, Rui L; Khademhosseini, Ali; Marques, Alexandra P; Gomes, Manuela E

2014-11-01

How to surpass in vitro stem cell differentiation, reducing cell manipulation, and lead the in situ regeneration process after transplantation, remains to be unraveled in bone tissue engineering (bTE). Recently, we showed that the combination of human bone marrow stromal cells with bioactive silicate nanoplatelets (sNPs) promotes the osteogenic differentiation without the use of standard osteogenic inductors. Even more, using SSEA-4(+) cell-subpopulations (SSEA-4(+)hASCs) residing within the adipose tissue, as a single-cellular source to obtain relevant cell types for bone regeneration, was also proposed. Herein, sNPs were used to promote the osteogenic differentiation of SSEA-4(+)hASCs. The interactions between SSEA-4(+)hASCs and sNPs, namely the internalization pathway and effect on cells osteogenic differentiation, were evaluated. SNPs below 100 μg/mL showed high cytocompatibility and fast internalization via clathrin-mediated pathway. SNPs triggered an overexpression of osteogenic-related markers (RUNX2, osteopontin, osteocalcin) accompanied by increased alkaline phosphatase activity and deposition of a predominantly collagen-type I matrix. Consequently, a robust matrix mineralization was achieved, covering >90% of the culturing surface area. Overall, we demonstrated the high osteogenic differentiation potential of SSEA-4(+)hASCs, further enhanced by the addition of sNPs in a dose dependent manner. This strategy endorses the combination of an adipose-derived cell-subpopulation with inorganic compounds to achieve bone matrix-analogs with clinical relevance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Field metabolic rate and PCB adipose tissue deposition efficiency in East Greenland polar bears derived from contaminant monitoring data.

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Viola Pavlova

Full Text Available Climate change will increasingly affect the natural habitat and diet of polar bears (Ursus maritimus. Understanding the energetic needs of polar bears is therefore important. We developed a theoretical method for estimating polar bear food consumption based on using the highly recalcitrant polychlorinated biphenyl (PCB congener, 2,2',4,4',55-hexaCB (CB153 in bear adipose tissue as an indicator of food intake. By comparing the CB153 tissue concentrations in wild polar bears with estimates from a purposely designed individual-based model, we identified the possible combinations of field metabolic rates (FMR and CB153 deposition efficiencies in East Greenland polar bears. Our simulations indicate that if 30% of the CB153 consumed by polar bear individuals were deposited into their adipose tissue, the corresponding FMR would be only two times the basal metabolic rate. In contrast, if the modelled CB153 deposition efficiency were 10%, adult polar bears would require six times more energy than that needed to cover basal metabolism. This is considerably higher than what has been assumed for polar bears in previous studies though it is similar to FMRs found in other marine mammals. An implication of this result is that even relatively small reductions in future feeding opportunities could impact the survival of East Greenland polar bears.

Novel gender-specific visceral adiposity index for Mexican pediatric population

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María J. Garcés

2014-10-01

Conclusions: VAI formula construction seemed to be different in children compared to adults. In the present study we propose a new gender-specific visceral adipose index for pediatric Mexican population living in urban areas that could be further used to predict abnormal cardiometabolic outcomes.

Efficient transduction of equine adipose-derived mesenchymal stem cells by VSV-G pseudotyped lentiviral vectors.

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Petersen, Gayle F; Hilbert, Bryan; Trope, Gareth; Kalle, Wouter; Strappe, Padraig

2014-12-01

Equine adipose-derived mesenchymal stem cells (EADMSC) provide a unique cell-based approach for treatment of a variety of equine musculoskeletal injuries, via regeneration of diseased or damaged tissue, or the secretion of immunomodulatory molecules. These capabilities can be further enhanced by genetic modification using lentiviral vectors, which provide a safe and efficient method of gene delivery. We investigated the suitability of lentiviral vector technology for gene delivery into EADMSC, using GFP expressing lentiviral vectors pseudotyped with the G glycoprotein from the vesicular stomatitis virus (V-GFP) or, for the first time, the baculovirus gp64 envelope protein (G-GFP). In this study, we produced similarly high titre V-GFP and G-GFP lentiviral vectors. Flow cytometric analysis showed efficient transduction using V-GFP; however G-GFP exhibited a poor ability to transduce EADMSC. Transduction resulted in sustained GFP expression over four passages, with minimal effects on cell viability and doubling time, and an unaltered chondrogenic differentiation potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relative abdominal adiposity is associated with chronic low back pain: a preliminary explorative study

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Cristy Brooks

2016-08-01

Full Text Available Abstract Background Although previous research suggests a relationship between chronic low back pain (cLBP and adiposity, this relationship is poorly understood. No research has explored the relationship between abdominal-specific subcutaneous and visceral adiposity with pain and disability in cLBP individuals. The aim of this study therefore was to examine the relationship of regional and total body adiposity to pain and disability in cLBP individuals. Methods A preliminary explorative study design of seventy (n = 70 adult men and women with cLBP was employed. Anthropometric and adiposity measures were collected, including body mass index, waist-to-hip ratio, total body adiposity and specific ultrasound-based abdominal adiposity measurements. Self-reported pain and disability were measured using a Visual Analogue Scale (VAS and the Oswestry Disability Index (ODI questionnaires respectively. Relationships between anthropometric and adiposity measures with pain and disability were assessed using correlation and regression analyses. Results Significant correlations between abdominal to lumbar adiposity ratio (A-L variables and the waist-to-hip ratio with self-reported pain were observed. A-L variables were found to predict pain, with 9.1–30.5 % of the variance in pain across the three analysis models explained by these variables. No relationships between anthropometric or adiposity variables to self-reported disability were identified. Conclusions The findings of this study indicated that regional distribution of adiposity via the A-L is associated with cLBP, providing a rationale for future research on adiposity and cLBP.

Adipose-derived stem cells - Methods and protocols

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Carlo Alberto Redi

2011-09-01

Full Text Available This book is pleasing the reader already by the Authors’ preface. It is one in a million case to find a figure or a graph in the foreword presentation of a book. Here, Professors Gimble and Bunnell decided to give a warning to the reader about the increasing relevance that the topics covered by the book is playing in the life sciences researches: they simply decided to show the ISI Web of knowledge annual publications and citations for adipose stem cells. Clear enough, the statistics is impressive: few papers in 2000, nearly 600 in 2009 and 2010. The same pattern is present in the citations per year, quite a few in 2000 – 2001 and something like 12,000 in 2010 ! I think that these numbers justify the idea to have a volume devoted to cover all of the topics related to these intriguing stem cell type, likely originating from a perivascular histological niche within highly vascularized fat tissue. The book is divided in four parts.......

Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

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Teresa G. Valencak

2017-08-01

Full Text Available Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders. Keywords: Body fatness, Adipose tissue, Sex-specific differences, Adipokines, Adipocytes, Obesity, Energy metabolism

The associations between adult body composition and abdominal adiposity outcomes, and relative weight gain and linear growth from birth to age 22 in the Birth to Twenty Plus cohort, South Africa.

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Prioreschi, Alessandra; Munthali, Richard J; Kagura, Juliana; Said-Mohamed, Rihlat; De Lucia Rolfe, Emanuella; Micklesfield, Lisa K; Norris, Shane A

2018-01-01

The growing prevalence of overweight and obesity in low- or middle-income countries precipitates the need to examine early life predictors of adiposity. To examine growth trajectories from birth, and associations with adult body composition in the Birth to Twenty Plus Cohort, Soweto, South Africa. Complete data at year 22 was available for 1088 participants (536 males and 537 females). Conditional weight and height indices were generated indicative of relative rate of growth between years 0-2, 2-5, 5-8, 8-18, and 18-22. Whole body composition was measured at year 22 (range 21-25 years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were recorded. Birth weight was positively associated with FFSTM and fat mass at year 22 (β = 0.11, page and being stunted at age 2 years were inversely associated with FFSTM at year 22. The importance of optimal birth weight and growth tempos during early life for later life body composition, and the detrimental effects of pre- and postnatal growth restriction are clear; yet contemporary weight-gain most strongly predicted adult body composition. Thus interventions should target body composition trajectories during childhood and prevent excessive weight gain in early adulthood.

Use of BMI as marker of adiposity in a metabolic syndrome severity score: derivation and validation in predicting long-term disease outcomes.

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Gurka, Matthew J; Filipp, Stephanie L; Musani, Solomon K; Sims, Mario; DeBoer, Mark D

2018-02-01

Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p BMI scores in their associations with future CHD and T2DM. A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time. Copyright © 2018. Published by Elsevier Inc.

Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation.

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Hamaguchi, Yuhei; Kaido, Toshimi; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Okajima, Hideaki; Uemoto, Shinji

2017-03-01

Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P mass index (P normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.

Making the switch: alternatives to foetal bovine serum for adipose-derived stromal cell expansion

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Carla Dessels

2016-10-01

Full Text Available Adipose-derived stromal cells (ASCs are being used extensively in clinical trials. These trials require that ASCs are prepared using good manufacturing procedures (GMPs and are safe for use in humans. The majority of clinical trials in which ASCs are expanded make use of fetal bovine serum (FBS. While FBS is used traditionally in the research setting for in vitro expansion, it does carry the risk of xenoimmunization and zoonotic transmission when used for expanding cells destined for therapeutic purposes. In order to ensure a GMP quality product for cellular therapy, in vitro expansion of ASCs has been undertaken using xeno-free (XF, chemically-defined, and human blood-derived alternatives. These investigations usually include the criteria proposed by the International Society of Cellular Therapy (ISCT and International Fat Applied Technology Society (IFATS. The majority of studies use these criteria to compare plastic-adherence, morphology, the immunophenotype and the trilineage differentiation of ASCs under the different medium supplemented conditions. Based on these studies, all of the alternatives to FBS seem to be suitable replacements; however, each has its own advantages and drawbacks. Very few studies have investigated the effects of the supplements on the immunomodulation of ASCs; the transcriptome, proteome and secretome; and the ultimate effects in appropriate animal models. The selection of medium supplementation will depend on the downstream application of the ASCs and their efficacy and safety in preclinical studies.

National Economic Development Status May Affect the Association between Central Adiposity and Cognition in Older Adults.

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Asri Maharani

Full Text Available Obesity is becoming a global problem, rather than one found only in developed countries. Although recent studies have suggested a detrimental effect of obesity on cognition, studies of the relationship between obesity and cognition among older adults have been limited to developed countries. We aimed to examine the associations between central obesity, as measured by waist circumference, and cognition level in adults aged 50 years and older in England and Indonesia.We used linear regression models to analyse these associations and multiple imputation to manage missing data. The 2006 English Longitudinal Study of Ageing Wave 3 is the source of data from England, while data from Indonesia is sourced from the 2007 Indonesian Family Life Survey Wave 4.Centrally obese respondents had lower cognition levels than non-centrally obese respondents in England. In contrast, central adiposity had a statistically significant positive association with cognition in Indonesia. Higher levels of education and higher economic status were associated with higher cognitive ability, while age was associated with lower cognition in both countries. Elevated C-reactive protein (CRP concentrations and smoking behaviour, both linked to higher risk of obesity, were negatively associated with cognitive ability among older adults in England, but they had no statistically significant association with cognition among Indonesians.The contradictory findings on obesity and cognition in England and Indonesia not only create a puzzle, but they may also have different policy implications in these countries. Reducing the prevalence of obesity may be the main focus in England and other developed countries to maintain older adults' cognition. However, Indonesia and other developing countries should place more emphasis on education, in addition to continued efforts to tackle the double burden of malnutrition, in order to prevent cognitive impairment among older adults.

Agreement between specific measures of adiposity and associations with high blood pressure in black South African women.

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Kruger, Herculina S; Botha-Ravyse, Chrisna; Havemann-Nel, Lize; Doubell, Maretha; van Rooyen, Johannes M

2017-11-01

To derive percentage body fat (%BF) cut-points according to body mass index (BMI) categories for adult black South African women and to investigate the agreement between adiposity classifications according to WHO BMI and %BF cut-points. The secondary aim was to determine the association between these different adiposity measures and high blood pressure. Black women aged 29-65 years (n = 435) from Ikageng, South Africa, were included in this cross-sectional study. Socio-demographic and anthropometric data were collected (weight, height and BMI). %BF using dual-energy X-ray absorptiometry and blood pressure were measured. There was significant agreement between three %BF categories: low/normal (high blood pressure (OR = 1.75, 95% CI 1.09-2.81 versus OR = 1.92, 95% CI 1.15-3.23, respectively). Despite significant agreement between BMI and %BF categories, considerable misclassification occurred in the overweight range. Participants with excessive %BF had a greater odds of high blood pressure than those in the highest BMI category. © 2017 Wiley Periodicals, Inc.

Influence of segmental body composition and adiposity hormones on resting metabolic rate and substrate utilization in overweight and obese adults.

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Hirsch, K R; Smith-Ryan, A E; Blue, M N M; Mock, M G; Trexler, E T

2017-06-01

Low resting metabolic rate (RMR) and high carbohydrate reliance at rest are associated with weight gain, but are highly variable in obese individuals. This study determined the relationship of total and segmental body composition and adiposity hormones with RMR and respiratory exchange ratio (RER) in overweight and obese adults. In 49 men (n = 23) and premenopausal women (n = 26) [mean ± SD; age = 35.0 ± 8.9 years; body mass index (BMI) = 33.6 ± 5.2 kg·m -2 ; percent body fat (%fat) = 40.0 ± 8.0%], RMR and RER were evaluated using indirect calorimetry. Total and segmental body composition [fat mass (FM), percent fat (%fat), lean mass (LM), visceral adipose tissue (VAT)] were estimated using dual-energy X-ray absorptiometry. Fasted blood and saliva samples were analyzed for insulin, leptin, estradiol, and cortisol. In men (M) and women (W), RMR significantly correlated (p  0.05). Segmental evaluation of body composition, specifically in the lower extremities and abdomen, may be an effective and efficient way to evaluate metabolic status. Sex-specific evaluations are also imperative.

Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment

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Kvido Smitka

2015-01-01

Full Text Available Adipose tissue is recognized as an active endocrine organ that produces a number of endocrine substances referred to as “adipokines” including leptin, adiponectin, adipolin, visfatin, omentin, tumour necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, resistin, pigment epithelium-derived factor (PEDF, and progranulin (PGRN which play an important role in the food intake regulation and significantly influence insulin sensitivity and in some cases directly affect insulin resistance in skeletal muscle, liver, and adipose tissue. The review summarizes current knowledge about adipose tissue-derived hormones and their influence on energy homeostasis regulation. The possible therapeutic potential of these adipokines in the treatment of insulin resistance, endothelial dysfunction, a pro-inflammatory response, obesity, eating disorders, progression of atherosclerosis, type 1 diabetes, and type 2 diabetes is discussed.

Brown adipose tissue in young adults who were born preterm or small for gestational age.

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Kistner, Anna; Rydén, Henric; Anderstam, Björn; Hellström, Ann; Skorpil, Mikael

2018-06-27

Brown adipose tissue (BAT) is present and functions to dissipate energy as heat in young adults and can be assessed using magnetic resonance imaging (MRI) to estimate the voxel fat fraction, i.e. proton density fat fraction (PDFF). It is hypothesized that subjects born preterm or small for gestational age (SGA) may exhibit disrupted BAT formation coupled to metabolic factors. Our purpose was to assess the presence of BAT in young adults born extremely preterm or SGA in comparison with controls. We studied 30 healthy subjects (median age, 21 years): 10 born extremely preterm, 10 full term but SGA and 10 full term with a normal birth weight (controls). We utilized an MRI technique combining multiple scans to enable smaller echo spacing and an advanced fat-water separation method applying graph cuts to estimate B0 inhomogeneity. We measured supraclavicular/cervical PDFF, R2*, fat volume, insulin-like growth factor 1, glucagon, thyroid stimulating hormone and the BAT-associated hormones fibroblast growth factor 21 and irisin. The groups did not significantly differ in supraclavicular/cervical PDFF, R2*, fat volume or hormone levels. The mean supraclavicular/cervical PDFF was equivalent between the groups (range 75-77%). Young adults born extremely preterm or SGA show BAT development similar to those born full term at a normal birth weight. Thus, the increased risk of cardiovascular and metabolic disorders in these groups is not due to the absence of BAT, although our results do not exclude possible BAT involvement in this scenario. Larger studies are needed to understand these relationships.

Adipose-derived mesenchymal stromal cells prevented rat vocal fold scarring.

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Morisaki, Tsuyoshi; Kishimoto, Yo; Tateya, Ichiro; Kawai, Yoshitaka; Suzuki, Ryo; Tsuji, Takuya; Hiwatashi, Nao; Nakamura, Tatsuo; Omori, Koichi; Kitano, Hiroya; Takeuchi, Hiromi; Hirano, Shigeru

2018-01-01

This study aimed to reveal the effects of adipose-derived mesenchymal stromal cells (ASCs) on prevention of vocal fold scarring by investigating how the immediate ASCs transplantation into the injured rat vocal fold affect the levels of gene transcription and translation. Prospective animal experiments with controls. ASCs harvested from green fluorescent protein transgenic rat (ASCs group) or saline (sham group) were injected into the thyroarytenoid muscle of Sprague-Dawley rats immediately after stripping the vocal fold. For histological examinations, larynges were extirpated at 3, 14, and 56 days after the injection. Quantitative real-time polymerase chain reaction (PCR) analyses were performed at 3 and 14 days after the injection. Transplanted ASCs were detected only in larynges at day 3. At days 14 and 56, histological examination showed significantly higher amounts of hyaluronic acid and lower deposition of collagen in the ASCs group compared to the sham group. Real-time PCR revealed that the ASCs group showed low expression of procollagen (Col)1a1, Col1a3, matrix metalloproteinase (Mmp)1 and Mmp8 in each time points. The ASCs group showed high expression of fibroblast growth factor (Fgf)2 and Hepatocyte growth factor (Hgf) compared to the sham group at day 14. ASCs increased expressions of Fgf2 and Hgf, and suppressed excessive collagen deposition during vocal fold wound healing. Given the fact that ASCs survived no more than 14 days, ASCs were thought to induce upregulations of growth factors' genes in surrounding cells. These results suggested that ASCs have potential to prevent vocal fold scarring. NA. Laryngoscope, 128:E33-E40, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Influence on Adiposity and Atherogenic Lipaemia of Fatty Meals and Snacks in Daily Life

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Laguna-Camacho, Antonio

2017-01-01

The present work reviewed the connections of changes in consumption of high-fat food with changes in adiposity and lipaemia in adults with overweight or obesity. Hyperlipaemia from higher fat meals and excessive adiposity contributes to atherogenic process. Low-fat diet interventions decrease body fat, lipaemia, and atherosclerosis markers. Inaccuracy of physical estimates of dietary fat intake remains, however, a limit to establishing causal connections. To fill this gap, tracking fat-rich e...

Heparin-immobilized hydroxyapatite nanoparticles as a lactoferrin delivery system for improving osteogenic differentiation of adipose-derived stem cells

International Nuclear Information System (INIS)

Kim, Sung Eun; Yun, Young-Pil; Kim, Hak-Jun; Lee, Deok-Won; Shim, Kyu-Sik; Jeon, Daniel I; Rhee, Jin-Kyu; Park, Kyeongsoon

2016-01-01

The aim of this study is to fabricate lactoferrin (LF)-carrying hydroxyapatite nanoparticles (HAp NPs) to enhance osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). HAp NPs were modified with heparin-dopamine (Hep-DOPA) (Hep-HAp) and further immobilized with LF (LF/Hep-HAp). Heparin immobilization on HAp NPs prevented aggregation of HAp NPs in aqueous solution and prolonged the release of LF from LF/Hep-HAp NPs. In vitro studies of rADSCs have demonstrated that LF-Hep/HAp NPs significantly increase alkaline phosphatase (ALP) activity, calcium deposition, and both mRNA expression of osteocalcin (OCN) and osteopontin (OPN) in comparison with HAp and Hep-HAp NPs. These results suggest that LF/Hep-HAp NPs can effectively induce osteogenic differentiation of rADSCs. (paper)

Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

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Shengchang Zhang

Full Text Available INTRODUCTION: Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. MATERIALS AND METHODS: Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP-expressing ASCs, aminoguanidine (AG or phosphate-buffered saline (PBS. Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD and malondialdehyde (MDA. RESULTS: Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. CONCLUSIONS: These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

Extensive characterization and comparison of endothelial cells derived from dermis and adipose tissue : Potential use in tissue engineering

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Monsuur, H.N.; Weijers, E.M.; Niessen, F.B.; Gefen, A.; Koolwijk, P.; Gibbs, S.; van den Broek, L.J.

2016-01-01

Tissue-engineered constructs need to become quickly vascularized in order to ensure graft take. One way of achieving this is to incorporate endothelial cells (EC) into the construct. The adipose tissue stromal vascular fraction (adipose-SVF) might provide an alternative source for endothelial cells

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

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Salamon, Achim; van Vlierberghe, Sandra; van Nieuwenhove, Ine; Baudisch, Frank; Graulus, Geert-Jan; Benecke, Verena; Alberti, Kristin; Neumann, Hans-Georg; Rychly, Joachim; Martins, José C.; Dubruel, Peter; Peters, Kirsten

2014-01-01

Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies. PMID:28788517

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

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Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

2017-01-01

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

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Grgurevic, Lovorka; Christensen, Gitte Lund; Schulz, Tim J

2016-01-01

implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role...... homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been...

Human Adipose-Derived Mesenchymal Stem Cells Are Resistant to HBV Infection during Differentiation into Hepatocytes in Vitro

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Ying Wang

2014-04-01

Full Text Available The therapeutic methods for chronic hepatitis B are limited. The shortage of organ donors and hepatitis B virus (HBV reinfection obstruct the clinical application of orthotopic liver transplantation (OLT. In the present study, adipose-derived mesenchymal stem cells (AD-MSCs and bone marrow-derived mesenchymal stem cells (BM-MSCs were isolated from chronic hepatitis B patients and characterized for morphology, growth potency, surface phenotype and the differentiation potential. The results showed that both MSCs had adipogenic, osteogenic and neuron differentiation potential, and nearly all MSCs expressed CD105, CD44 and CD29. Compared with AD-MSCs, BM-MSCs of chronic hepatitis B patients proliferated defectively. In addition, the ability of AD-MSCs to differentiate into hepatocyte was evaluated and the susceptibility to HBV infection were assessed. AD-MSCs could differentiate into functional hepatocyte-like cells. These cells express the hepatic-specific markers and have glycogen production and albumin secretion function. AD-MSCs and hepatic differentiation AD-MSCs were not susceptible to infection by HBV in vitro. Compared with BM-MSCs, AD-MSCs may be alternative stem cells for chronic hepatitis B patients.

Childhood adiposity trajectories are associated with late adolescent blood pressure: birth to twenty cohort

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Richard J. Munthali

2016-07-01

Full Text Available Abstract Background Elevated blood pressure in childhood is a risk factor for adult hypertension which is a global health problem. Excess adiposity in childhood creates a predisposition to develop adult hypertension. Our aim was to explore distinct sex-specific adiposity trajectories from childhood to late adolescence and examined their association with blood pressure. Methods Latent Class Growth Mixture Modeling (LCGMM on longitudinal data was used to derive sex-specific and distinct body mass index (BMI: kg/m2 trajectories. We studied 1824 black children (boys = 877, girls = 947 from the Birth to Twenty (Bt20 cohort from Soweto, South Africa, and obtained BMI measures at ages 5 through 18 years. Participants with at least two age-point BMI measures, were included in the analysis. Analysis of variance (ANOVA, chi-square test, multivariate linear and standard logistic regressions were used to test study characteristics and different associations. Results We identified three (3 and four (4 distinct BMI trajectories in boys and girls, respectively. The overall prevalence of elevated blood pressure (BP was 34.9 % (39.4 % in boys and 30.38 % in girls. Boys and girls in the early onset obesity or overweight BMI trajectories were more likely to have higher BP values in late adolescence. Compared to those in the normal weight BMI trajectory, girls in early onset obesity trajectories had an increased risk of elevated BP with odds ratio (OR of 2.18 (95 % confidence interval 1.31 to 4.20 and 1.95 (1.01 to 3.77. We also observed the weak association for boys in early onset overweight trajectory, (p-value = 0.18 and odds ratio of 2.39 (0.67 to 8.57 Conclusions Distinct weight trajectories are observed in black South African children from as early as 5 years. Early onset adiposity trajectories are associated with elevated BP in both boys and girls. It is important to consider individual patterns of early-life BMI development, so that

Alcohol, Adipose Tissue and Lipid Dysregulation

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Jennifer L. Steiner

2017-02-01

Full Text Available Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long‐term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged. Study of the lipolytic and lipogenic pathways has identified several regulatory proteins modulated by alcohol that contribute to these effects. Glucose tolerance of adipose tissue is also impaired by chronic alcohol due to decreased glucose transporter‐4 availability at the membrane. As an endocrine organ, white adipose tissue (WAT releases several adipokines that are negatively modulated following chronic alcohol consumption including adiponectin, leptin, and resistin. When these effects are combined with the enhanced expression of inflammatory mediators that are induced by chronic alcohol, a proinflammatory state develops within WAT, contributing to the observed lipodystrophy. Lastly, while chronic alcohol intake may enhance thermogenesis of brown adipose tissue (BAT, definitive mechanistic evidence is currently lacking. Overall, both WAT and BAT depots are impacted by chronic alcohol intake and the resulting lipodystrophy contributes to fat accumulation in peripheral organs, thereby enhancing the pathological state accompanying chronic alcohol use disorder.

Molecular characterization of adipose tissue in the African elephant (Loxodonta africana.

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Emeli M Nilsson

Full Text Available Adipose tissue (AT is a dynamic and flexible organ with regulatory roles in physiological functions including metabolism, reproduction and inflammation; secreted adipokines, including leptin, and fatty acids facilitate many of these roles. The African elephant (Loxodonta africana is experiencing serious challenges to optimal reproduction in captivity. The physiological and molecular basis of this impaired fertility remains unknown. AT production of leptin is a crucial molecular link between nutritional status, adiposity and fertility in many species. We propose that leptin has a similar function in the African elephant. African elephant visceral and subcutaneous adipose tissue (AT was obtained from both sexes and a range of ages including females with known pregnancy status. RNA was extracted and histological sections created and analyzed by microarray, PCR and immunohistochemistry respectively. Gas-chromatography was used to determine the fatty acid composition of AT. Microarray expression profiling was used to compare gene expression profiles of AT from pre-pubertal versus reproductively competent adult African elephants. This study demonstrates, for the first time, leptin mRNA and protein expression in African elephant AT. The derived protein sequence of the elephant leptin protein was exploited to determine its relationship within the class I helical cytokine superfamily, which indicates that elephant leptin is most closely related to the leptin orthologs of Oryctolagus cuniculus (European rabbit, Lepus oiostolus (woolly hare, and members of the Ochotonidae (Pika. Immunohistological analysis identified considerable leptin staining within the cytoplasm of adipocytes. Significant differences in fatty acid profiles between pregnant and non-pregnant animals were revealed, most notably a reduction in both linoleic and α linoleic acid in pregnant animals. This report forms the basis for future studies to address the effect of nutrient composition

The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis.

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Dirk Vissers

Full Text Available Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with "The Critical Review Form for Quantitative Studies". Using random-effects weights, the standardized mean difference (Hedge's g of the change in visceral adipose tissue was -0.497 with a 95% confidence interval of -0.655 to -0.340. The Z-value was -6.183 and the p-value (two tailed was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm(2 (on CT analysis in women and more than 40 cm(2 in men, even after 12 weeks.

Infrapatellar Fat Pad: An Alternative Source of Adipose-Derived Mesenchymal Stem Cells

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P. Tangchitphisut

2016-01-01

Full Text Available Introduction. The Infrapatellar fat pad (IPFP represents an emerging alternative source of adipose-derived mesenchymal stem cells (ASCs. We compared the characteristics and differentiation capacity of ASCs isolated from IPFP and SC. Materials and Methods. ASCs were harvested from either IPFP or SC. IPFPs were collected from patients undergoing total knee arthroplasty (TKA, whereas subcutaneous tissues were collected from patients undergoing lipoaspiration. Immunophenotypes of surface antigens were evaluated. Their ability to form colony-forming units (CFUs and their differentiation potential were determined. The ASCs karyotype was evaluated. Results. There was no difference in the number of CFUs and size of CFUs between IPFP and SC sources. ASCs isolated from both sources had a normal karyotype. The mesenchymal stem cells (MSCs markers on flow cytometry was equivalent. IPFP-ASCs demonstrated significantly higher expression of SOX-9 and RUNX-2 over ASCs isolated from SC (6.19 ± 5.56-, 0.47 ± 0.62-fold; p value = 0.047, and 17.33 ± 10.80-, 1.56 ± 1.31-fold; p value = 0.030, resp.. Discussion and Conclusion. CFU assay of IPFP-ASCs and SC-ASCs harvested by lipoaspiration technique was equivalent. The expression of key chondrogenic and osteogenic genes was increased in cells isolated from IPFP. IPFP should be considered a high quality alternative source of ASCs.

Interaction of FTO and physical activity level on adiposity in African-American and European-American adults: the ARIC study.

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Demerath, Ellen W; Lutsey, Pam L; Monda, Keri L; Linda Kao, Wen Hong; Bressler, Jan; Pankow, James S; North, Kari E; Folsom, Aaron R

2011-09-01

Physical inactivity accentuates the association of variants in the FTO locus with obesity-related traits but evidence is largely lacking in non-European populations. Here we tested the hypothesis that physical activity (PA) modifies the association of the FTO single-nucleotide polymorphism (SNP) rs9939609 with adiposity traits in 2,656 African Americans (AA) (1,626 women and 1,030 men) and 9,867 European Americans (EA) (5,286 women and 4,581 men) aged 45-66 years in the Atherosclerosis Risk in Communities (ARIC) study. Individuals in the lowest quintile of the sport activity index of the Baecke questionnaire were categorized as low PA. Baseline BMI, waist circumference (WC), and skinfold measures were dependent variables in regression models testing the additive effect of the SNP, low PA, and their interaction, adjusting for age, alcohol use, cigarette use, educational attainment, and percent European ancestry in AA adults, stratified by sex and race/ethnicity. rs9939609 was associated with adiposity in all groups other than AA women. The SNP × PA interaction was significant in AA men (P ≤ 0.002 for all traits) and EA men (P ≤ 0.04 for all traits). For each additional copy of the A (risk) allele, WC in AA men was higher in those with low PA (β(lowPA): 5.1 cm, 95% confidence interval (CI): 2.6-7.5) than high PA (β(highPA): 0.7 cm, 95% CI: -0.4 to 1.9); P (interaction) = 0.002). The interaction effect was not observed in EA or AA women. FTO SNP × PA interactions on adiposity were observed for AA as well as EA men. Differences by sex require further examination.

Function of microRNAs in the Osteogenic Differentiation and Therapeutic Application of Adipose-Derived Stem Cells (ASCs

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Walter M. Hodges

2017-12-01

Full Text Available Traumatic wounds with segmental bone defects represent substantial reconstructive challenges. Autologous bone grafting is considered the gold standard for surgical treatment in many cases, but donor site morbidity and associated post-operative complications remain a concern. Advances in regenerative techniques utilizing mesenchymal stem cell populations from bone and adipose tissue have opened the door to improving bone repair in the limbs, spine, and craniofacial skeleton. The widespread availability, ease of extraction, and lack of immunogenicity have made adipose-derived stem cells (ASCs particularly attractive as a stem cell source for regenerative strategies. Recently it has been shown that small, non-coding miRNAs are involved in the osteogenic differentiation of ASCs. Specifically, microRNAs such as miR-17, miR-23a, and miR-31 are expressed during the osteogenic differentiation of ASCs, and appear to play a role in inhibiting various steps in bone morphogenetic protein-2 (BMP2 mediated osteogenesis. Importantly, a number of microRNAs including miR-17 and miR-31 that act to attenuate the osteogenic differentiation of ASCs are themselves stimulated by transforming growth factor β-1 (TGFβ-1. In addition, transforming growth factor β-1 is also known to suppress the expression of microRNAs involved in myogenic differentiation. These data suggest that preconditioning strategies to reduce TGFβ-1 activity in ASCs may improve the therapeutic potential of ASCs for musculoskeletal application. Moreover, these findings support the isolation of ASCs from subcutaneous fat depots that tend to have low endogenous levels of TGFβ-1 expression.

Increased risk of subclinical atherosclerosis associated with high visceral adiposity index in apparently healthy Korean adults: the Kangbuk Samsung Health Study.

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Park, Hye-Jeong; Kim, Jihyun; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

2016-09-01

The visceral adiposity index (VAI) is a mathematical tool that reflects a patient's visceral adiposity and insulin resistance. Recent studies have noted an association between VAI and cardiovascular event. We analyzed the association between VAI and coronary artery calcium score (CACS) in Korean adults. For 33,468 participants (mean age 42 yrs) in a health screening program, VAI was calculated using the following formulae: [waist circumference (WC)/{39.68 + (1.88 * body mass index (BMI))}] * (triglyceride/1.03) * {1.31/high-density lipoprotein cholesterol (HDL-C)} for men and [WC/{36.58 + (1.89 * BMI)}] * (triglyceride/0.81) * (1.52/HDL-C) for women. Coronary artery calcium scores were measured with multi-detector computed tomography. CACS was positively correlated with VAI (r = 0.027, p 0 as the dependent variable, subjects in the highest tertile of VAI (>1.777) had significantly increased odds ratio for CACS >0 compared to subjects in the lowest tertile (<0.967), even after adjusting for confounding variables, including BMI (OR 1.26, 95% CI 1.147-1.381). Subjects with high VAI had increased risk for subclinical atherosclerosis, as assessed by CACS. Key messages Recent studies have noted an association between visceral adiposity index (VAI) and cardiovascular event. Subjects with coronary artery calcification (CAC) showed significantly higher VAI compared to those without CAC. The subjects with high VAI showed increased odds ratio for CAC as compared to subjects with low VAI, suggesting high VAI reflects increased risk for subclinical atherosclerosis.

Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase

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Silvia Baldari

2016-07-01

Full Text Available Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs, suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2. Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.

Long-term outcome of adipose-derived regenerative cell-enriched autologous fat transplantation for reconstruction after breast-conserving surgery for Japanese women with breast cancer.

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Ito, Shuhei; Kai, Yuichiro; Masuda, Takaaki; Tanaka, Fumiaki; Matsumoto, Toshifumi; Kamohara, Yukio; Hayakawa, Hiroshi; Ueo, Hiroaki; Iwaguro, Hideki; Hedrick, Marc H; Mimori, Koshi; Mori, Masaki

2017-12-01

More effective methods are needed for breast reconstruction after breast-conserving surgery for breast cancer. The aim of this clinical study was to assess the perioperative and long-term outcomes of adipose-derived regenerative cell (ADRC)-enriched autologous fat grafting. Ten female patients who had undergone breast-conserving surgery and adjuvant radiotherapy for breast cancer were enrolled. An ADRC-enriched fat graft prepared from the patient's adipose tissue was implanted at the time of adipose tissue harvest. The perioperative and long-term outcomes of the grafts, which included safety, efficacy, and questionnaire-based patient satisfaction, were investigated. The mean operation time was 188 ± 30 min, and the mean duration of postoperative hospitalization was 1.2 ± 0.4 days. No serious postoperative complications were associated with the procedure. Neither recurrence nor metastatic disease was observed during the follow-up period (7.8 ± 1.5 years) after transplantation. Of 9 available patients, "more than or equal to average" satisfaction with breast appearance and overall satisfaction were reported by 6 (66.7%) and 5 (55.6%) patients, respectively. ADRC-enriched autologous fat transplantation is thus considered to be safe perioperatively, with no long-term recurrence, for patients with breast cancer treated by breast-conserving surgery, and it may be an option for breast reconstruction, even after adjuvant radiotherapy.

Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells

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Pasarica, Magdalena; Mashtalir, Nazar; McAllister, Emily J

2008-01-01

Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity......, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly...... greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade-CCAAT/Enhancer binding protein...

Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily breakfast consumption in lean and obese adults.

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Gonzalez, Javier T; Richardson, Judith D; Chowdhury, Enhad A; Koumanov, Francoise; Holman, Geoffrey D; Cooper, Scott; Thompson, Dylan; Tsintzas, Kostas; Betts, James A

2018-02-15

In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal adipose tissue. In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue. The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting. Therefore, any observations of altered adipose tissue insulin sensitivity with extended morning fasting do not necessarily require changes in insulin signalling proximal to Akt. Insulin-stimulated adipose tissue glucose uptake rates are lower in obese versus lean individuals, but this difference is abolished when values are normalised to whole-body fat mass. This suggests a novel hypothesis which proposes that the reduced adipose glucose uptake in obesity is a physiological down-regulation to prevent excessive de novo lipogenesis. This study assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty-nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily breakfast consumption (BFAST; ≥700 kcal before 11.00 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin-stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were up-regulated with FAST versus BFAST (ACADM: 1.14 (95% CI: 0.97-1.30) versus 0.80 (95% CI: 0.64-0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33-2.16) versus 1.09 (95% CI: 0.67-1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all

Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

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Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China); Tang, Zhi-hui, E-mail: tang_zhihui@live.cn [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China)

2015-05-29

Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human Adipose-Derived Stem Cells

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Bo Kyung Sun

2015-07-01

Full Text Available Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA, significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation.

Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human Adipose-Derived Stem Cells

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Sun, Bo Kyung; Kim, Ji Hye; Choi, Joon-Seok; Hwang, Sung-Joo; Sung, Jong-Hyuk

2015-01-01

Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs) or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA), significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation. PMID:26204837

Cholinergic and dopaminergic neuronal differentiation of human adipose tissue derived mesenchymal stem cells.

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Marei, Hany El Sayed; El-Gamal, Aya; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Farag, Amany; Cenciarelli, Carlo; Thomas, Caceci; Anwarul, Hasan

2018-02-01

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types such as cartilage, bone, and fat cells. Recent studies have shown that induction of MSCs in vitro by growth factors including epidermal growth factor (EGF) and fibroblast growth factor (FGF2) causes them to differentiate into neural like cells. These cultures also express ChAT, a cholinergic marker; and TH, a dopaminergic marker for neural cells. To establish a protocol with maximum differentiation potential, we examined MSCs under three experimental culture conditions using neural induction media containing FGF2, EGF, BMP-9, retinoic acid, and heparin. Adipose-derived MSCs were extracted and expanded in vitro for 3 passages after reaching >80% confluency, for a total duration of 9 days. Cells were then characterized by flow cytometry for CD markers as CD44 positive and CD45 negative. MSCs were then treated with neural induction media and were characterized by morphological changes and Q-PCR. Differentiated MSCs expressed markers for immature and mature neurons; β Tubulin III (TUBB3) and MAP2, respectively, showing the neural potential of these cells to differentiate into functional neurons. Improved protocols for MSCs induction will facilitate and ensure the reproducibility and standard production of MSCs for therapeutic applications in neurodegenerative diseases. © 2017 Wiley Periodicals, Inc.

Osteogenic differentiation of human adipose-derived mesenchymal stem cells on gum tragacanth hydrogel.

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Haeri, Seyed Mohammad Jafar; Sadeghi, Yousef; Salehi, Mohammad; Farahani, Reza Masteri; Mohsen, Nourozian

2016-05-01

Currently, natural polymer based hydrogels has attracted great attention of orthopedic surgeons for application in bone tissue engineering. With this aim, osteoinductive capacity of Gum Tragacanth (GT) based hydrogel was compared to collagen hydrogel and tissue culture plate (TCPS). For this purpose, adipose-derived mesenchymal stem cells (AT-MSCs) was cultured on the hydrogels and TCPS and after investigating the biocompatibility of hydrogels using MTT assay, osteoinductivity of hydrogels were evaluated using pan osteogenic markers such as Alizarin red staining, alkaline phosphatase (ALP) activity, calcium content and osteo-related genes. Increasing proliferation trend of AT-MSCs on GT hydrogel demonstrated that TG has no-cytotoxicity and can even be better than the other groups i.e., highest proliferation at day 5. GT hydrogel displayed highest ALP activity and mineralization when compared to the collagen hydrogel and TCPS. Relative gene expression levels have demonstrated that highest expression of Runx2, osteonectin and osteocalcin in the cells cultured GT hydrogel but the expression of collagen type-1 remains constant in hydrogels. Above results demonstrate that GT hydrogel could be an appropriate scaffold for accelerating and supporting the adhesion, proliferation and osteogenic differentiation of stem cells which further can be used for orthopedic applications. Copyright © 2016. Published by Elsevier Ltd.

Deviation of Chinese Adults' Diet from the Chinese Food Pagoda 2016 and Its Association with Adiposity.

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Tian, Xu; Huang, Yingying; Wang, Hui

2017-09-08

Changing diet in China contributes to a raising prevalence of overweight and obesity. This study aimed to evaluate the dietary status of Chinese adults (20-59 years old) using the China Food Pagoda (CFP) proposed in the Chinese Dietary Guidelines 2016 (CDG), and investigate the association between adiposity and deviation of real diet from CFP using an ordered logistic regression. Results showed that the consumption of fruits, eggs, meat, and poultry increased significantly during 2004-2011, while the consumption of cereal, potatoes, and beans dropped down significantly during the same period (all p associated with a higher risk of having high body mass index (BMI), while lower consumption of cereal, potatoes and beans, eggs, and higher consumption of vegetables contributed to low hazard of overweight/obesity (all p < 0.05). The huge disparity between real consumption and the CFP calls for specific health education campaigns.

Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

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Christian Cortés-Campos

2015-09-01

Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

Relationships between rodent white adipose fat pads and human white adipose fat depots

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Daniella E. Chusyd

2016-04-01

Full Text Available The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of white adipose tissue. Thus, further research is warranted to more carefully define the strengths and limitations of rodent white adipose tissue as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat.

Cardiac regeneration by pharmacologically active microcarriers releasing growth factors and/or transporting adipose-derived stem cells

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Monia Savi

2014-01-01

Full Text Available We tested the hypothesis that cardiac regeneration through local delivery of adipose-derived stem cells (ASCs, activation of resident cardiac stem cells via growth factors (GFs [hepatocyte growth factor (HGF and insulin-like growth factor 1 (IGF-1:GFs] or both, are improved by pharmacologically active microcarriers (PAMs interacting with cells/molecules conveyed on their surface. Rats with one-month old myocardial infarction were treated with ASCs, ASCs+PAMs, GF-releasing PAMs, ASCs+GF-releasing PAMs or vehicle. Two weeks later, hemodynamic function and inducibility of ventricular arrhythmias (VAs were assessed. Eventually, the hearts were subjected to anatomical and immunohistochemical analyses. A significant ASCs engraftment and the largest improvement in cardiac mechanics occurred in ASC+GF-releasing PAM rats which by contrast were more vulnerable to VAs. Thus, PAMs may improve cell/GF-based cardiac regeneration although caution should be paid on the electrophysiological impact of their physical interaction with the myocardium.

Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

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Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

2007-01-01

For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

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Achim Salamon

2014-02-01

Full Text Available Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies.

Purification and differentiation of human adipose-derived stem cells by membrane filtration and membrane migration methods

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Lin, Hong Reng; Heish, Chao-Wen; Liu, Cheng-Hui; Muduli, Saradaprasan; Li, Hsing-Fen; Higuchi, Akon; Kumar, S. Suresh; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Hsu, Shih-Tien; Chen, Da-Chung; Benelli, Giovanni; Murugan, Kadarkarai; Cheng, Nai-Chen; Wang, Han-Chow; Wu, Gwo-Jang

2017-01-01

Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not. PMID:28071738

Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells

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Zhou Zhou

2012-12-01

Full Text Available Abstract Background Leptin-deficient ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Methods Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells. Results We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3 Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells. Conclusions Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies.

Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

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Douglas L. de Almeida

2013-12-01

Full Text Available Background/Aims: Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Methods: Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups and small (3 pups litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Results: Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C and dark (NL 38°C vs. SL 37.6°C periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (pConclusion: Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults.

A paper-based scaffold for enhanced osteogenic differentiation of equine adipose-derived stem cells.

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Petersen, Gayle F; Hilbert, Bryan J; Trope, Gareth D; Kalle, Wouter H J; Strappe, Padraig M

2015-11-01

We investigated the applicability of single layer paper-based scaffolds for the three-dimensional (3D) growth and osteogenic differentiation of equine adipose-derived stem cells (EADSC), with comparison against conventional two-dimensional (2D) culture on polystyrene tissue culture vessels. Viable culture of EADSC was achieved using paper-based scaffolds, with EADSC grown and differentiated in 3D culture retaining high cell viability (>94 %), similarly to EADSC in 2D culture. Osteogenic differentiation of EADSC was significantly enhanced in 3D culture, with Alizarin Red S staining and quantification demonstrating increased mineralisation (p < 0.0001), and an associated increase in expression of the osteogenic-specific markers alkaline phosphatase (p < 0.0001), osteopontin (p < 0.0001), and runx2 (p < 0.01). Furthermore, scanning electron microscopy revealed a spherical morphology of EADSC in 3D culture, compared to a flat morphology of EADSC in 2D culture. Single layer paper-based scaffolds provide an enhanced environment for the in vitro 3D growth and osteogenic differentiation of EADSC, with high cell viability, and a spherical morphology.

[Use of adipose-derived stem cells in an experimental rotator cuff fracture animal model].

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Barco, R; Encinas, C; Valencia, M; Carrascal, M T; García-Arranz, M; Antuña, S

2015-01-01

Rotator cuff repairs have shown a high level of re-ruptures. We hypothesized that the use of adipose-derived stem cells (ASC) could improve the biomechanical and histological properties of the repair. Controlled experimental study conducted on 44 BDIX rats with section and repair of the supraspinatus tendon and randomization to one of three groups: group A, no intervention (control); group B, local applications of a fibrin sealant; and group C, application of the fibrin sealant with 2 x 10(6) ASC. At 4 and 8 weeks a biomechanical and histological analysis was performed. There were no differences in load-to-failure at 4 and 8 weeks between groups. The load-to-failure did increase between week 4 and week 8. Histologically the tendon-to bone union showed a disorganized fibrovascular tissue. Group C showed a different inflammatory pattern, with less presence of neutrophils and more presence of plasma cells. The use of ASC does not improve the biomechanical or histological properties of the repair site. More studies are needed to improve techniques that enhance the healing site of the repair. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

MicroRNA-1 Regulates the Differentiation of Adipose-Derived Stem Cells into Cardiomyocyte-Like Cells

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Can Chen

2018-01-01

Full Text Available Stem cell transplantation is one of most valuable methods in the treatment of myocardial infarction, and adipose-derived stem cells (ASCs are becoming a hot topic in medical research. Previous studies have shown that ASCs can be differentiated into cardiomyocyte-like cells, but the efficiency and survival rates are low. We investigated the role and mechanism of microRNA-1 (miR-1 in the differentiation of ASCs into cardiomyocyte-like cells. ASCs and cardiomyocytes were isolated from neonatal rats. We constructed lentivirus for overexpressing miR-1 and used DAPT, an antagonist of the Notch1 pathway, for in vitro analyses. We performed cocultures with ASCs and cardiomyocytes. The differentiation efficiency of ASCs was detected by cell-specific surface antigens. Our results showed that miR-1 can promote the expression of Notch1 and reduce the expression of Hes1, a Notch pathway factor, and overexpression of miR-1 can promote the differentiation of ASCs into cardiomyocyte-like cells, which may occur by regulating Notch1 and Hes1.

In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.

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Xie, Lin; Zhang, Nan; Marsano, Anna; Vunjak-Novakovic, Gordana; Zhang, Yanru; Lopez, Mandi J

2013-12-01

Directed differentiation of adult multipotent stromal cells (MSC) is critical for effective treatment strategies. This study was designed to evaluate the capability of equine MSC from bone marrow (BMSC) and adipose tissue (ASC) on a type I collagen (COLI) scaffold to undergo chondrogenic, osteogenic and adipogenic differentiation and form extracellular matrix (ECM) in vitro. Following determination of surface antigen expression, MSC were loaded into scaffolds in a perfusion bioreactor and loading efficiency was quantified. Cell-scaffold constructs were assessed after loading and 7, 14 and 21 days of culture in stromal or induction medium. Cell number was determined with DNA content, cell viability and spatial uniformity with confocal laser microscopy and cell phenotype and matrix production with light and scanning electron microscopy and mRNA levels. The MSC were positive for CD29 (>90 %), CD44 (>99 %), and CD105 (>60 %). Loading efficiencies were >70 %. The ASC and BMSC cell numbers on scaffolds were affected by culture in induction medium differently. Viable cells remained uniformly distributed in scaffolds for up to 21 days and could be directed to differentiate or to maintain an MSC phenotype. Micro- and ultrastructure showed lineage-specific cell and ECM changes. Lineage-specific mRNA levels differed between ASC and BMSC with induction and changed with time. Based on these results, equine ASC and BMSC differentiate into chondrogenic, osteogenic and adipogenic lineages and form ECM similarly on COLI scaffolds. The collected data supports the potential for equine MSC-COLI constructs to support diverse equine tissue formation for controlled biological studies.

Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture

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Phetfong, J.; Tawonsawatruk, T.; Seenprachawong, K.; Srisarin, A.; Isarankura-Na-Ayudhya, C.

2017-01-01

Objectives Adipose-derived mesenchymal stem cells (ADMSCs) are a promising strategy for orthopaedic applications, particularly in bone repair. Ex vivo expansion of ADMSCs is required to obtain sufficient cell numbers. Xenogenic supplements should be avoided in order to minimise the risk of infections and immunological reactions. Human platelet lysate and human plasma may be an excellent material source for ADMSC expansion. In the present study, use of blood products after their recommended transfusion date to prepare human platelet lysate (HPL) and human plasma (Hplasma) was evaluated for in vitro culture expansion and osteogenesis of ADMSCs. Methods Human ADMSCs were cultured in medium supplemented with HPL, Hplasma and a combination of HPL and Hplasma (HPL+Hplasma). Characteristics of these ADMSCs, including osteogenesis, were evaluated in comparison with those cultured in fetal bovine serum (FBS). Results HPL and HPL+Hplasma had a significantly greater growth-promoting effect than FBS, while Hplasma exhibited a similar growth-promoting effect to that of FBS. ADMSCs cultured in HPL and/or Hplasma generated more colony-forming unit fibroblasts (CFU-F) than those cultured in FBS. After long-term culture, ADMSCs cultured in HPL and/or Hplasma showed reduced cellular senescence, retained typical cell phenotypes, and retained differentiation capacities into osteogenic and adipogenic lineages. Conclusion HPL and Hplasma prepared from blood products after their recommended transfusion date can be used as an alternative and effective source for large-scale ex vivo expansion of ADMSCs. Cite this article: J. Phetfong, T. Tawonsawatruk, K. Seenprachawong, A. Srisarin, C. Isarankura-Na-Ayudhya, A. Supokawej. Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture. Bone Joint Res 2017;6:414–422. DOI: 10.1302/2046-3758.67.BJR-2016-0342.R1. PMID:28720606

Identification and characterization of a supraclavicular brown adipose tissue in mice

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A fundamental challenge to our understanding of brown adipose tissue (BAT) is the lack of an animal model that faithfully represents human BAT. Such a model is essential for direct assessment of the function and therapeutic potential of BAT depots in humans. In human adults, most of the thermoactive...

Some Adipose Derived Hormones in Association with the Risk of Knee Osteoarthritis

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Mehdi Moghtadae

2017-04-01

Full Text Available Background Knee osteoarthritis (OA is the most common form of arthritis and is the major cause of pain and disability in the elderly. The relationship between obesity and increased risk of knee osteoarthritis was known for many years. Since then, many studies have shown the relationship between knee osteoarthritis and obesity. Objectives In this study, we tried to evaluate whether compared to weight, the adipose tissue has a stronger correlation with the occurrence of knee osteoarthritis. Methods In a cross-sectional study that was a part of the Fasa knee osteoarthritis registry (FOAS, 131 patients with OA were sex matched with 262 patients in the control group. Serum samples of the patients, the Western Ontario and McMaster universities arthritis index (WOMAC questionnaire and demographic data were collected. Leptin and adiponectin as hormones secreted by the adipose tissue were measured. Results Weight, body mass index (BMI, and waist circumference (WC were significantly different between the two groups (P < 0.001. The Kellgren and Lawrence (K&L score was significantly higher among the patients (P < 0.001. Pain levels in patients with OA were also significantly higher compared to those in the control group (P < 0.001. Both leptin and adiponectin concentrations were higher in the OA patients. Adiponectin had a negative relationship with BMI in the OA group (r = 0.570, P < 0.001, but leptin had a positive relationship with BMI (r = 0.781, P < 0.001. In the OA group, both adipokines had higher levels in female patients compared to male patients. Conclusions The results of the current study showed that levels of hormones secreted from the adipose tissue, in people with knee OA, were higher compared to the control group, indicating the possible effect of these hormones on the process of osteoarthritis. Finally, we showed that after adjusting for age, sex, and BMI, leptin and adiponectin are significantly correlated with the amount of pain

Three-Dimensional Graphene–RGD Peptide Nanoisland Composites That Enhance the Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells

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Ee-Seul Kang

2018-02-01

Full Text Available Graphene derivatives have immense potential in stem cell research. Here, we report a three-dimensional graphene/arginine-glycine-aspartic acid (RGD peptide nanoisland composite effective in guiding the osteogenesis of human adipose-derived mesenchymal stem cells (ADSCs. Amine-modified silica nanoparticles (SiNPs were uniformly coated onto an indium tin oxide electrode (ITO, followed by graphene oxide (GO encapsulation and electrochemical deposition of gold nanoparticles. A RGD–MAP–C peptide, with a triple-branched repeating RGD sequence and a terminal cysteine, was self-assembled onto the gold nanoparticles, generating the final three-dimensional graphene–RGD peptide nanoisland composite. We generated substrates with various gold nanoparticle–RGD peptide cluster densities, and found that the platform with the maximal number of clusters was most suitable for ADSC adhesion and spreading. Remarkably, the same platform was also highly efficient at guiding ADSC osteogenesis compared with other substrates, based on gene expression (alkaline phosphatase (ALP, runt-related transcription factor 2, enzyme activity (ALP, and calcium deposition. ADSCs induced to differentiate into osteoblasts showed higher calcium accumulations after 14–21 days than when grown on typical GO-SiNP complexes, suggesting that the platform can accelerate ADSC osteoblastic differentiation. The results demonstrate that a three-dimensional graphene–RGD peptide nanoisland composite can efficiently derive osteoblasts from mesenchymal stem cells.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

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LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

Comparison of local adipose tissue content and SRS-derived NIRS muscle oxygenation measurements in 90 individuals.

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Cooper, Chris E; Penfold, Stacey-Marie; Elwell, Clare E; Angus, Caroline

2010-01-01

Adipose content in the region over the vastus lateralis muscle was measured in a young (21.1 +/- 3.1 years old, mean +/- SD) population of males (n = 62) and females (n = 28). Three techniques were used: skinfold thickness, ultrasound and near infrared spectroscopy. All techniques closely correlated with each other and all showed a significantly larger adipose content in females and a limited overlap with the range of values in males. Spatially resolved near infrared spectroscopy (SRS-NIRS) was then used to measure the tissue oxygenation index (TOI) at the same site. A source-detector separation of 4 cm was used to allow for significant light penetration into muscle tissue. TOI at rest was significantly higher in the female (65.3 +/- 7.0, mean +/- SD) than the male (61.9 +/- 5.1, mean +/- SD) group. There was a strong positive correlation between adipose content and TOI in male subjects. However, no correlation was seen in the female group. The possible optical and physiological explanations for these results are discussed.

Hyaluronic acid effect on adipose-derived stem cells. Biological in vitro evaluation.

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Moreno, A; Martínez, A; Olmedillas, S; Bello, S; de Miguel, F

2015-01-01

To evaluate the in vitro effects of hyaluronic acid (HA) on adipose-derived stem cells (ASC) in order to consider the possibility of their combined used in the treatment of knee arthrosis. The ASC cells were grown both in the presence and absence of AH, and several studies were carried out: proliferation (WST8) and cell viability studies (Alamar Blue® and Trypan Blue), possible chondrogenic differentiation (collagen type 2 expression) by RT-PCR, AH receptor expression (CD44) by flow cytometry and RT-QPCR, and expression of inflammatory and anti-inflammatory factors (IL-6, TGFß, IL-10) by RT-QPCR. The number of ASC significantly increased after 7 days with HA (158±39%, p <0.05). Additionally, the cell viability of the ASC treated with HA after 1, 3, 5 and 7 days was similar to that of the control cells, being considered non-toxic. There were no changes observed in the expression of CD44 and chondrogenic differentiation. TGFß expression was not modified after AH treatment, but there was a 4-fold decrease in IL-6 expression and IL-10 expression increased up to 2-fold compared to control cells. Hyaluronic acid favours ASC proliferation without causing cellular toxicity, and inducing an anti-inflammatory profile in these cells. Hyaluronic acid appears to be a suitable vehicle for the intra-articular administration of mesenchymal stem cells. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells

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Maravillas Mellado-López

2017-01-01

Full Text Available Adipose-derived stem cells (ASCs are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway

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The goal was to examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), Beta-cell function, and SAT gene expression. SAT biopsies were obtained from...

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

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Nahyun Choi

2018-02-01

Full Text Available Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs. We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif ligand 1 (CXCL1, platelet-derived endothelial cell growth factor (PD-ECGF, and platelet-derived growth factor-C (PDGF-C. Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2 phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

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Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

2018-01-01

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction.

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Sun, Cheuk-Kwan; Zhen, Yen-Yi; Leu, Steve; Tsai, Tzu-Hsien; Chang, Li-Teh; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Tan; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

2014-05-15

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The association between higher maternal pre-pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn.

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McCloskey, K; Ponsonby, A-L; Collier, F; Allen, K; Tang, M L K; Carlin, J B; Saffery, R; Skilton, M R; Cheung, M; Ranganathan, S; Dwyer, T; Burgner, D; Vuillermin, P

2018-01-01

Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults; however, little is known regarding the determinants of adiposity-related inflammation at birth. The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. Paired maternal (28-week gestation) and infant (umbilical cord) blood samples were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m -2 , 95% CI 6.6 to 28.9; p = 0.002), newborn mean skin-fold thickness (mean difference 0.1 mm per kg m -2 , 95% CI 0.0 to 0.1; p pregnancy BMI, 95% CI 0.6 to 7.7%, p = 0.02), but not cord blood soluble CD14. Inclusion of maternal hsCRP as a covariate attenuated the associations between pre-pregnancy BMI and both newborn skin-fold thickness and cord blood hsCRP. Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy. © 2016 World Obesity Federation.

Magnetic resonance imaging tracking of human adipose derived stromal cells within three-dimensional scaffolds for bone tissue engineering

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C Lalande

2011-04-01

Full Text Available For bone tissue engineering, human Adipose Derived Stem Cells (hADSCs are proposed to be associated with a scaffold for promoting bone regeneration. After implantation, cellularised scaffolds require a non-invasive method for monitoring their fate in vivo. The purpose of this study was to use Magnetic Resonance Imaging (MRI-based tracking of these cells, labelled with magnetic agents for in vivo longitudinal assessment. hADSCs were isolated from adipose tissue and labelled with USPIO-rhodamine (Ultrasmall SuperParamagnetic Iron Oxide. USPIO internalisation, absence of toxicity towards hADSCs, and osteogenic differentiation of the labelled cells were evaluated in standard culture conditions. Labelled cells were then seeded within a 3D porous polysaccharide-based scaffold and imaged in vitro using fluorescence microscopy and MRI. Cellularised scaffolds were implanted subcutaneously in nude mice and MRI analyses were performed from 1 to 28 d after implantation. In vitro, no effect of USPIO labelling on cell viability and osteogenic differentiation was found. USPIO were efficiently internalised by hADSCs and generated a high T2* contrast. In vivo MRI revealed that hADSCs remain detectable until 28 d after implantation and could migrate from the scaffold and colonise the area around it. These data suggested that this scaffold might behave as a cell carrier capable of both holding a cell fraction and delivering cells to the site of implantation. In addition, the present findings evidenced that MRI is a reliable technique to validate cell-seeding procedures in 3D porous scaffolds, and to assess the fate of hADSCs transplanted in vivo.

The Relationship of a Combination of Human Adipose Tissue-Derived Stem Cells and Frozen Fat with the Survival Rate of Transplanted Fat

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Ki-Young Ha

2015-11-01

Full Text Available BackgroundThe survival rate of grafted fat is difficult to predict, and repeated procedures are frequently required. In this study, the effects of the freezing period of harvested adipose tissue and the addition of human adipose tissue-derived stem cells (ASCs on the process of fat absorption were studied.MethodsAdipose tissue was obtained from patients who underwent a lipoaspirated fat graft. The fat tissue was cryopreserved at -20℃ in a domestic refrigerator. A total of 40 nude mice were used. The mice in the experimental group received three different subcutaneous injections in the back: an injection of fresh fat and ASCs, an injection of fat that had been frozen for one month and ASCs, and an injection of fat that had been frozen for two months and ASCs. The control mice received fat grafts without ASCs. The mice were sacrificed at four or eight weeks after the procedure, and the grafted fat tissues were harvested. The extracted fat was evaluated using photographic analysis, volume measurements, and histological examination.ResultsIn the control group, the fat resorption rates four weeks after transplantation in the grafts of fresh fat, fat that had been frozen for one month, and fat that had been frozen for two months were 21.14%, 22.46%, and 42.56%, respectively. In the experimental group, the corresponding resorption rates were 6.68%, 13.0%, and 33.9%, respectively.ConclusionsASCs can increase the fat graft survival rate. The use of ASCs in fat grafting can reduce the need for repeated fat grafts and provide good long term results.

A tale with a Twist: a developmental gene with potential relevance for metabolic dysfunction and inflammation in adipose tissue

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Anca Dana Dobrian

2012-08-01

Full Text Available The Twist proteins (Twist-1 and -2 are highly conserved developmental proteins with key roles for the transcriptional regulation in mesenchymal cell lineages. They belong to the super-family of bHLH proteins and exhibit bi-functional roles as both activators and repressors of gene transcription. The Twist proteins are expressed at low levels in adult tissues but may become abundantly re-expressed in cells undergoing malignant transformation. This observation prompted extensive research on the roles of Twist proteins in cancer progression and metastasis. Very recent studies indicate a novel role for Twist-1 as a potential regulator of adipose tissue remodeling and inflammation. Several studies suggested that developmental genes are important determinants of obesity, fat distribution and remodeling capacity of different adipose depots. Twist-1 is abundantly and selectively expressed in the adult adipose tissue and its constitutive expression is significantly higher in subcutaneous vs. visceral fat in both mice and humans. Moreover, Twist1 expression is strongly correlated with BMI and insulin resistance in humans. However, the functional roles and transcriptional downstream targets of Twist1 in adipose tissue are largely unexplored. The purpose of this review is to highlight the major findings related to Twist1 expression in different fat depots and cellular components of adipose tissue and to discuss the potential mechanisms suggesting a role for Twist1 in adipose tissue metabolism, inflammation and remodeling.

Hair follicle growth by stromal vascular fraction-enhanced adipose transplantation in baldness

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Perez-Meza D

2017-07-01

Full Text Available David Perez-Meza,1 Craig Ziering,2 Marcos Sforza,3 Ganesh Krishnan,4 Edward Ball,5 Eric Daniels6 1Ziering Medical, Marbella, Spain; 2Ziering Medical, Los Angeles, CA, USA; 3The Hospital Group, Bromsgrove, Worcestershire, 4Ziering Medical, Birmingham, 5Ziering Medical, London, UK; 6Kerastem Technologies, San Diego, CA, USA Abstract: Great interest remains in finding new and emerging therapies for the treatment of male and female pattern hair loss. The autologous fat grafting technique is >100 years old, with a recent and dramatic increase in clinical experience over the past 10–15 years. Recently, in 2001, Zuk et al published the presence of adipose-derived stem cells, and abundant research has shown that adipose is a complex, biological active, and important tissue. Festa et al, in 2011, reported that adipocyte lineage cells support the stem cell niche and help drive the complex hair growth cycle. Adipose-derived regenerative cells (also known as stromal vascular fraction [SVF] is a heterogeneous group of noncultured cells that can be reliably extracted from adipose by using automated systems, and these cells work largely by paracrine mechanisms to support adipocyte viability. While, today, autologous fat is transplanted primarily for esthetic and reconstructive volume, surgeons have previously reported positive skin and hair changes posttransplantation. This follicular regenerative approach is intriguing and raises the possibility that one can drive or restore the hair cycle in male and female pattern baldness by stimulating the niche with autologous fat enriched with SVF. In this first of a kind patient series, the authors report on the safety, tolerability, and quantitative, as well as photographic changes, in a group of patients with early genetic alopecia treated with subcutaneous scalp injection of enriched adipose tissue. The findings suggest that scalp stem cell-enriched fat grafting may represent a promising alternative approach to

Platelet-Rich Plasma Favors Proliferation of Canine Adipose-Derived Mesenchymal Stem Cells in Methacrylate-Endcapped Caprolactone Porous Scaffold Niches

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Victoria Moreno-Manzano

2012-08-01

Full Text Available Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy ethyl ester (CLMA scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration.

Platelet-Rich Plasma Favors Proliferation of Canine Adipose-Derived Mesenchymal Stem Cells in Methacrylate-Endcapped Caprolactone Porous Scaffold Niches

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Rodríguez-Jiménez, Francisco Javier; Valdes-Sánchez, Teresa; Carrillo, José M.; Rubio, Mónica; Monleon-Prades, Manuel; García-Cruz, Dunia Mercedes; García, Montserrat; Cugat, Ramón; Moreno-Manzano, Victoria

2012-01-01

Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs) have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF) treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration. PMID:24955632

In vitro differentiation of neural cells from human adipose tissue derived stromal cells.

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Dave, Shruti D; Patel, Chetan N; Vanikar, Aruna V; Trivedi, Hargovind L

2018-01-01

Stem cells, including neural stem cells (NSCs), are endowed with self-renewal capability and hence hold great opportunity for the institution of replacement/protective therapy. We propose a method for in vitro generation of stromal cells from human adipose tissue and their differentiation into neural cells. Ten grams of donor adipose tissue was surgically resected from the abdominal wall of the human donor after the participants' informed consents. The resected adipose tissue was minced and incubated for 1 hour in the presence of an enzyme (collagenase-type I) at 37 0 C followed by its centrifugation. After centrifugation, the supernatant and pellets were separated and cultured in a medium for proliferation at 37 0 C with 5% CO2 for 9-10 days in separate tissue culture dishes for generation of mesenchymal stromal cells (MSC). At the end of the culture, MSC were harvested and analyzed. The harvested MSC were subjected for further culture for their differentiation into neural cells for 5-7 days using differentiation medium mainly comprising of neurobasal medium. At the end of the procedure, culture cells were isolated and studied for expression of transcriptional factor proteins: orthodenticle homolog-2 (OTX-2), beta-III-tubulin (β3-Tubulin), glial-fibrillary acid protein (GFAP) and synaptophysin-β2. In total, 50 neural cells-lines were generated. In vitro generated MSC differentiated neural cells' mean quantum was 5.4 ± 6.9 ml with the mean cell count being, 5.27 ± 2.65 × 10 3/ μl. All of them showed the presence of OTX-2, β3-Tubulin, GFAP, synaptophysin-β2. Neural cells can be differentiated in vitro from MSC safely and effectively. In vitro generated neural cells represent a potential therapy for recovery from spinal cord injuries and neurodegenerative disease.

Creation of an Adiposity Index for Children Aged 6–8 Years: The Gateshead Millennium Study

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Mark S. Pearce

2013-01-01

Full Text Available Objective. A number of measures of childhood adiposity are in use, but all are relatively imprecise and prone to bias. We constructed an adiposity index (AI using a number of different measures. Methods. Detailed body composition data on 460 of the Gateshead Millennium Study cohort at the age of 6–8 years were analysed. The AI was calculated using factor analysis on age plus thirteen measures of adiposity and/or size. Correlations between these variables, the AI, and more traditional measures of adiposity in children were investigated. Results. Based on the factor loading sizes, the first component, taken to be the AI, consisted mainly of measures of fat-mass (the skinfold measurements, fat mass score, and waist circumference. The second comprised variables measuring frame size, while the third consisted mainly of age. The AI had a high correlation with body mass index (BMI (rho = 0.81. Conclusions. While BMI is practical for assessing adiposity in children, the AI combines a wider range of data related to adiposity than BMI alone and appears both valid and valuable as a research tool for studies of childhood adiposity. Further research is necessary to investigate the utility of AI for research in other samples of children and also in adults.

Characterization of human adipose tissue-derived stem cells in vitro culture and in vivo differentiation in a temperature-sensitive chitosan/β- glycerophosphate/collagen hybrid hydrogel

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Song, Kedong, E-mail: Kedongsong@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Li, Liying; Yan, Xinyu; Zhang, Wen; Zhang, Yu [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Wang, Yiwei [Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW, 2139 (Australia); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China)

2017-01-01

In this study, the interaction of human adipose tissue-derived stem cells (ADSCs) with chitosan/β-glycerophosphate/collagen (C/GP/Co) hybrid hydrogel was test, followed by investigating the capability of engineered adipose tissue formation using this ADSCs seeded hydrogel. The ADSCs were harvested and mixed with a C/GP/Co hydrogel followed by a gelation at 37 °C and an in vitro culture. The results showed that the ADSCs within C/GP/Co hydrogels achieved a 30% of expansion over 7 days in culture medium and encapsulated cell in C/GP/Co hydrogel demonstrated a characteristic morphology with high viability over 5 days. C/GP/Co hydrogel were subcutaneous injected into SD-rats to assess the biocompatibility. The induced ADSCs-C/GP/Co hydrogel and non-induced ADSCs-C/GP/Co hydrogel were subcutaneously injected into nude mice for detecting potential of adipogenic differentiation. It has shown that C/GP/Co hydrogel were well tolerated in SD rats where they had persisted over 4 weeks post implantation. Histology analysis indicated that induced ADSCs-C/GP/Co hydrogel has a greater number of adipocytes and vascularized adipose tissues compared with non-induced ADSCs-C/GP/Co hydrogel. - Highlights: • The hydrogel scaffold was produced using chitosan, β-glycerophosphate and collagen. • This novel hydrogel is in liquid phase at low temperature and is gelatinized at 37 °C. • The new hydrogel provides ADSCs a favorable 3D environment with highly maintenance of proliferation and cytoactive. • ADSCs seeded hydrogel differentiated into adipose tissue, indicating favorable ability of adipogenesis. • This attractive property of C/GP/CO hydrogel points to its value as an excellent scaffold for tissue engineering.

The suitability of human adipose-derived stem cells for the engineering of ligament tissue.

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Eagan, Michael J; Zuk, Patricia A; Zhao, Ke-Wei; Bluth, Benjamin E; Brinkmann, Elyse J; Wu, Benjamin M; McAllister, David R

2012-10-01

Rupture of the anterior cruciate ligament (ACL) is the one of the most common sports-related injuries. With its poor healing capacity, surgical reconstruction using either autografts or allografts is currently required to restore function. However, serious complications are associated with graft reconstructions and the number of such reconstructions has steadily risen over the years, necessitating the search for an alternative approach to ACL repair. Such an approach may likely be tissue engineering. Recent engineering approaches using ligament-derived fibroblasts have been promising, but the slow growth rate of such fibroblasts in vitro may limit their practical application. More promising results are being achieved using bone marrow mesenchymal stem cells (MSCs). The adipose-derived stem cell (ASC) is often proposed as an alternative choice to the MSC and, as such, may be a suitable stem cell for ligament engineering. However, the use of ASCs in ligament engineering still remains relatively unexplored. Therefore, in this study, the potential use of human ASCs in ligament tissue engineering was initially explored by examining their ability to express several ligament markers under growth factor treatment. ASC populations treated for up to 4 weeks with TGFβ1 or IGF1 did not show any significant and consistent upregulation in the expression of collagen types 1 and 3, tenascin C and scleraxis. While treatment with EGF or bFGF resulted in increased tenascin C expression, increased expression of collagens 1 and 3 were never observed. Therefore, simple in vitro treatment of human ASC populations with growth factors may not stimulate their ligament differentiative potential. Copyright © 2011 John Wiley & Sons, Ltd.

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

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Cecilia M Lindgren

2009-06-01

Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

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Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone–fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues – subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT – is differently associated wi...

Enzymatically crosslinked gelatin hydrogel promotes the proliferation of adipose tissue-derived stromal cells

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Gang Yang

2016-09-01

Full Text Available Gelatin hydrogel crosslinked by microbial transglutaminase (mTG exhibits excellent performance in cell adhesion, proliferation, and differentiation. We examined the gelation time and gel strength of gelatin/mTG hydrogels in various proportions to investigate their physical properties and tested their degradation performances in vitro. Cell morphology and viability of adipose tissue-derived stromal cells (ADSCs cultured on the 2D gel surface or in 3D hydrogel encapsulation were evaluated by immunofluorescence staining. Cell proliferation was tested via Alamar Blue assay. To investigate the hydrogel effect on cell differentiation, the cardiac-specific gene expression levelsof Nkx2.5, Myh6, Gja1, and Mef2c in encapsulated ADSCs with or without cardiac induction medium were detected by real-time RT-PCR. Cell release from the encapsulated status and cell migration in a 3D hydrogel model were assessed in vitro. Results show that the gelatin/mTG hydrogels are not cytotoxic and that their mechanical properties are adjustable. Hydrogel degradation is related to gel concentration and the resident cells. Cell growth morphology and proliferative capability in both 2D and 3D cultures were mainly affected by gel concentration. PCR result shows that hydrogel modulus together with induction medium affects the cardiac differentiation of ADSCs. The cell migration experiment and subcutaneous implantation show that the hydrogels are suitable for cell delivery.

Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

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Francesco Perdisa

2015-01-01

Full Text Available Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview of in vivo studies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

Possibility of Undifferentiated Human Thigh Adipose Stem Cells Differentiating into Functional Hepatocytes

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Jong Hoon Lee

2012-11-01

Full Text Available BackgroundThis study aimed to investigate the possibility of isolating mesenchymal stem cells (MSCs from human thigh adipose tissue and the ability of human thigh adipose stem cells (HTASCs to differentiate into hepatocytes.MethodsThe adipose-derived stem cells (ADSCs were isolated from thigh adipose tissue. Growth factors, cytokines, and hormones were added to the collagen coated dishes to induce the undifferentiated HTASCs to differentiate into hepatocyte-like cells. To confirm the experimental results, the expression of hepatocyte-specific markers on undifferentiated and differentiated HTASCs was analyzed using reverse transcription polymerase chain reaction and immunocytochemical staining. Differentiation efficiency was evaluated using functional tests such as periodic acid schiff (PAS staining and detection of the albumin secretion level using enzyme-linked immunosorbent assay (ELISA.ResultsThe majority of the undifferentiated HTASCs were changed into a more polygonal shape showing tight interactions between the cells. The differentiated HTASCs up-regulated mRNA of hepatocyte markers. Immunocytochemical analysis showed that they were intensely stained with anti-albumin antibody compared with undifferentiated HTASCs. PAS staining showed that HTASCs submitted to the hepatocyte differentiation protocol were able to more specifically store glycogen than undifferentiated HTASCs, displaying a purple color in the cytoplasm of the differentiated HTASCs. ELISA analyses showed that differentiated HTASCs could secrete albumin, which is one of the hepatocyte markers.ConclusionsMSCs were islolated from human thigh adipose tissue differentiate to heapatocytes. The source of ADSCs is not only abundant abdominal adipose tissue, but also thigh adipose tissue for cell therapy in liver regeneration and tissue regeneration.

Human Adipose-Derived Mesenchymal Stem Cells Respond to Short-Term Hypoxia by Secreting Factors Beneficial for Human Islets In Vitro and Potentiate Antidiabetic Effect In Vivo

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Schive, Simen W.; Mirlashari, Mohammad Reza; Hasvold, Grete; Wang, Mengyu; Josefsen, Dag; Gullestad, Hans Petter; Korsgren, Olle; Foss, Aksel; Kvalheim, Gunnar; Scholz, Hanne

2017-01-01

Adipose-derived mesenchymal stem cells (ASCs) release factors beneficial for islets in vitro and protect against hyperglycemia in rodent models of diabetes. Oxygen tension has been shown to induce metabolic changes and alter ASCs? release of soluble factors. The effects of hypoxia on the antidiabetic properties of ASCs have not been explored. To investigate this, we incubated human ASCs for 48 h in 21% (normoxia) or 1% O2 (hypoxia) and compared viability, cell growth, surface markers, differe...

Proinflammatory interleukins' production by adipose tissue-derived mesenchymal stromal cells: the impact of cell culture conditions and cell-to-cell interaction.

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Andreeva, Elena; Andrianova, Irina; Rylova, Julia; Gornostaeva, Aleksandra; Bobyleva, Polina; Buravkova, Ludmila

2015-08-01

The impact of culture conditions and interaction with activated peripheral blood mononuclear cells on the interleukin (IL) gene expression profile and proinflammatory IL-6 and IL-8 production by adipose-derived stromal cells (ASCs) was investigated. A microarray analysis revealed a wide range of IL genes either under standard (20%) or hypoxic (5%) O2 concentrations, some highly up-regulated at hypoxia. IL-6 and IL-8 production was inversely dependent on cell culture density. In early (first-third) passages, IL-6 and IL-8 concentration was higher at 20% O2 and in late (8th-12th) passages under 5% O2. Interaction between ASCs and mononuclear cells in indirect setting was accompanied with a significant decrease of IL-6 and did not result in the elevation of IL-8 concentration. Thereby, the production of proinflammatory interleukins (IL-6 and IL-8) may be affected by the ASC intrinsic features (density in culture, and duration of expansion), as well as by microenvironmental factors, such as hypoxia and the presence of blood-borne cells. These data are important for elucidating ASC paracrine activity regulation in vitro. They would also be on demand for optimisation of the cell therapy protocols, based on the application of ASC biologically active substances. SIGNIFICANCE PARAGRAPH: Ex vivo expansion is widely used for increasing the number of adipose-derived stromal cells (ASCs) and improving of their quality. The present study was designed to elucidate the particular factors influencing the interleukin production in ASCs. The presented data specified the parameters (i.e. cell density, duration of cultivation, hypoxia, etc.) that should be taken in mind when ASCs are intended to be used in protocols implying their paracrine activity. These data would be of considerable interest for researchers and clinicians working in the biomedical science. Copyright © 2015 John Wiley & Sons, Ltd.

Association between dietary phytochemical index and 3-year changes in weight, waist circumference and body adiposity index in adults: Tehran Lipid and Glucose study

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Mirmiran Parvin

2012-12-01

Full Text Available Abstract Background High intakes of phytochemical-rich foods have favorable effects on the prevention of chronic diseases. In this study we assessed the dietary phytochemical index (PI in relation to 3-year change in weight, waist circumference (WC, body adiposity index (BAI among Tehranian adults. Methods This longitudinal study was conducted in the framework of Tehran Lipid and Glucose Study, between 2006–2008 and 2009–2011, on 1938 adults, aged 19–70 y. The usual intake of participants was measured at baseline using a validated semi-quantitative food frequency questionnaire and dietary PI was calculated. Anthropometric measures were assessed both at baseline and 3 years later. Multiple regression models were used to estimate mean difference changes in anthropometrics associated with various dietary PI. Results The mean age of participants was 40.4 ± 13.0 y, at baseline, respectively. Mean weight gain was 1.49 ± 5.06 kg (1.65 ± 5.3 kg in men and 1.34 ± 4.9 kg in women during 3-year period. After adjustment for potential confounding variables including age at baseline, sex, BMI, educational levels, smoking, physical activity, total energy intake, dietary intake of carbohydrate, fat and protein, dietary intakes of whole grains in the highest quartile category of PI were inversely associated with 3-year changes in weight and WC (P for trend . Dietary intake of fruits in the highest quartile was also associated with lower weight gain during the study period (P for trend . There was significant inverse association between the highest quartile category of dietary PI with the 3-year changes in weight and BAI (P for trend . Conclusion Higher dietary PI could have favorable effects on prevention of weight gain and reduction of body adiposity in adults.

Influence on Adiposity and Atherogenic Lipaemia of Fatty Meals and Snacks in Daily Life

Directory of Open Access Journals (Sweden)

Antonio Laguna-Camacho

2017-01-01

Full Text Available The present work reviewed the connections of changes in consumption of high-fat food with changes in adiposity and lipaemia in adults with overweight or obesity. Hyperlipaemia from higher fat meals and excessive adiposity contributes to atherogenic process. Low-fat diet interventions decrease body fat, lipaemia, and atherosclerosis markers. Inaccuracy of physical estimates of dietary fat intake remains, however, a limit to establishing causal connections. To fill this gap, tracking fat-rich eating episodes at short intervals quantifies the behavioural frequency suggested to measure (by regression of changes in real time direct effects of this eating pattern on adiposity and atherogenic lipaemia. Such evidence will provide the basis for an approach focused on a sustained decrease in frequency of fatty meals or snacks to reduce obesity, hyperlipaemia, and atherosclerosis.

Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts

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Miguel Tofiño-Vian

2017-01-01

Full Text Available Osteoarthritis (OA affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL- 1β indicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associated β-galactosidase activity and the accumulation of γH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.

Science.gov (United States)

Zolochevska, Olga; Shearer, Joseph; Ellis, Jayne; Fokina, Valentina; Shah, Forum; Gimble, Jeffrey M; Figueiredo, Marxa L

2014-03-01

Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells. ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays. ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs. These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

In vivo cell tracking imaging of hexadecyl-4-[{sup 123,} {sup 124}I]iodobenzoate labeled adipose derived stem cells (ADSCs) in rat heart

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Kim, Min Hwan; Lee, Yong Jin; Lee, Kyo Chul [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2011-10-15

Monitoring of transplanted stem cells for cardiac repair is important part in regenerative medicine. Direct cell labeling techniques using [{sup 18}F]FDG, [{sup 64}Cu]PTSM and [{sup 99m}Tc]-HMPAO have been developed for in vivo imaging. Especially, {sup 18}F-labeled derivates have been widely used for direct labeling agent. But the {sup 18}F has short half life (T{sub 1/2}={approx}2 h), thus this imaging agent has limitation of in vivo imaging. We used {sup 123}I or {sup 124}I which has relative long half life, to track the transplanted stem cells for a long-term imaging. This study is aimed to track the transplanted adipose derived stem cells (ADSCs) in rat heart using hexadecyl-4-[{sup 123,} {sup 124}I]iodobenzoate ([{sup 123,} {sup 124}I]HIB) mediated direct labeling method in vivo

Adhesion, vitality and osteogenic differentiation capacity of adipose derived stem cells seeded on nitinol nanoparticle coatings.

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Sarah Strauss

Full Text Available Autologous cells can be used for a bioactivation of osteoimplants to enhance osseointegration. In this regard, adipose derived stem cells (ASCs offer interesting perspectives in implantology because they are fast and easy to isolate. However, not all materials licensed for bone implants are equally suited for cell adhesion. Surface modifications are under investigation to promote cytocompatibility and cell growth. The presented study focused on influences of a Nitinol-nanoparticle coating on ASCs. Possible toxic effects as well as influences on the osteogenic differentiation potential of ASCs were evaluated by viability assays, scanning electron microscopy, immunofluorescence and alizarin red staining. It was previously shown that Nitinol-nanoparticles exert no cell toxic effects to ASCs either in soluble form or as surface coating. Here we could demonstrate that a Nitinol-nanoparticle surface coating enhances cell adherence and growth on Nitinol-surfaces. No negative influence on the osteogenic differentiation was observed. Nitinol-nanoparticle coatings offer new possibilities in implantology research regarding bioactivation by autologous ASCs, respectively enhancement of surface attraction to cells.

Induction of osteogenic differentiation of adipose derived stem cells by microstructured nitinol actuator-mediated mechanical stress.

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Sarah Strauß

Full Text Available The development of large tissue engineered bone remains a challenge in vitro, therefore the use of hybrid-implants might offer a bridge between tissue engineering and dense metal or ceramic implants. Especially the combination of the pseudoelastic implant material Nitinol (NiTi with adipose derived stem cells (ASCs opens new opportunities, as ASCs are able to differentiate osteogenically and therefore enhance osseointegration of implants. Due to limited knowledge about the effects of NiTi-structures manufactured by selective laser melting (SLM on ASCs the study started with an evaluation of cytocompatibility followed by the investigation of the use of SLM-generated 3-dimensional NiTi-structures preseeded with ASCs as osteoimplant model. In this study we could demonstrate for the first time that osteogenic differentiation of ASCs can be induced by implant-mediated mechanical stimulation without support of osteogenic cell culture media. By use of an innovative implant design and synthesis via SLM-technique we achieved high rates of vital cells, proper osteogenic differentiation and mechanically loadable NiTi-scaffolds could be achieved.

Enhanced osteogenesis of adipose derived stem cells with Noggin suppression and delivery of BMP-2.

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Jiabing Fan

Full Text Available Bone morphogenetic proteins (BMPs are believed to be the most potent osteoinductive factors. However, BMPs are highly pleiotropic molecules and their supra-physiological high dose requirement leads to adverse side effects and inefficient bone formation. Thus, there is a need to develop alternative osteoinductive growth factor strategies that can effectively complement BMP activity. In this study, we intrinsically stimulated BMP signaling in adipose derived stem cells (ASCs by downregulating noggin, a potent BMP antagonist, using an RNAi strategy. ASCs transduced with noggin shRNA significantly enhanced osteogenic differentiation of cells. The potency of endogenous BMPs was subsequently enhanced by stimulating ASCs with exogenous BMPs at a significantly reduced dose. The level of mineralization in noggin shRNA treated ASCs when treated with BMP-2 was comparable to that of control shRNA treated cell treated with 10-fold more BMP-2. The complementary strategy of noggin suppression + BMP-2 to enhance osteogenesis was further confirmed in 3D in vitro environments using scaffolds consisting of chitosan (CH, chondroitin sulfate (CS, and apatite layer on their surfaces designed to slowly release BMP-2. This finding supports the novel therapeutic potential of this complementary strategy in bone regeneration.

Human Adipose Derived Stem Cells Induced Cell Apoptosis and S Phase Arrest in Bladder Tumor

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Xi Yu

2015-01-01

Full Text Available The aim of this study was to determine the effect of human adipose derived stem cells (ADSCs on the viability and apoptosis of human bladder cancer cells. EJ and T24 cells were cocultured with ADSCs or cultured with conditioned medium of ADSCs (ADSC-CM, respectively. The cell counting and colony formation assay showed ADSCs inhibited the proliferation of EJ and T24 cells. Cell viability assessment revealed that the secretions of ADSCs, in the form of conditioned medium, were able to decrease cancer cell viability. Wound-healing assay suggested ADSC-CM suppressed migration of T24 and EJ cells. Moreover, the results of the flow cytometry indicated that ADSC-CM was capable of inducing apoptosis of T24 cells and inducing S phase cell cycle arrest. Western blot revealed ADSC-CM increased the expression of cleaved caspase-3 and cleaved PARP, indicating that ADSC-CM induced apoptosis in a caspase-dependent way. PTEN/PI3K/Akt pathway and Bcl-2 family proteins were involved in the mechanism of this reaction. Our study indicated that ADSCs may provide a promising and practicable manner for bladder tumor therapy.

Impact of adipose tissue or umbilical cord derived mesenchymal stem cells on the immunogenicity of human cord blood derived endothelial progenitor cells.

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Kefang Tan

Full Text Available The application of autologous endothelial progenitor cell (EPC transplantation is a promising approach in therapeutic cardiovascular diseases and ischemic diseases. In this study, we compared the immunogenicity of EPCs, adipose tissue (AD-derived mesenchymal stem cells (MSCs and umbilical cord (UC-derived MSCs by flow cytometry and the mixed lymphocyte reaction. The impact of AD-MSCs and UC-MSCs on the immunogenicity of EPCs was analyzed by the mixed lymphocyte reaction and cytokine secretion in vitro and was further tested by allogenic peripheral blood mononuclear cell (PBMC induced immuno-rejection on a cell/matrigel graft in an SCID mouse model. EPCs and AD-MSCs express higher levels of MHC class I than UC-MSCs. All three kinds of cells are negative for MHC class II. UC-MSCs also express lower levels of IFN-γ receptor mRNA when compared with EPCs and AD-MSCs. EPCs can stimulate higher rates of proliferation of lymphocytes than AD-MSCs and UC-MSCs. Furthermore, AD-MSCs and UC-MSCs can modulate immune response and inhibit lymphocyte proliferation induced by EPCs, mainly through inhibition of the proliferation of CD8+ T cells. Compared with UC-MSCs, AD-MSCs can significantly improve vessel formation and maintain the integrity of neovascular structure in an EPC+MSC/matrigel graft in SCID mice, especially under allo-PBMC induced immuno-rejection. In conclusion, our study shows that AD-MSC is a powerful candidate to minimize immunological rejection and improve vessel formation in EPC transplantation treatment.

Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

DEFF Research Database (Denmark)

Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

2013-01-01

Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) ......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in rats.

Science.gov (United States)

de Almeida, Douglas L; Fabrício, Gabriel S; Trombini, Amanda B; Pavanello, Audrei; Tófolo, Laize P; da Silva Ribeiro, Tatiane A; de Freitas Mathias, Paulo C; Palma-Rigo, Kesia

2013-01-01

Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (p<0.01), and no difference was observed in the sympathetic nerve activity. In adulthood, the small litter rats were 11,7% heavier than the controls and presented higher glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults. © 2013 S. Karger AG, Basel.

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

International Nuclear Information System (INIS)

Akita, S.; Yoshimoto, H.; Ohtsuru, A.; Hirano, A.; Yamashita, S.

2012-01-01

Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6±14.9 y (52-89 y), with mean radiation dose of 75.0±35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6±1.3 x 10 7 cells were obtained. All cases healed uneventfully after 6.6±3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9±0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds. (authors)

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

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Akita, S; Yoshimoto, H [Div. of Plastic and Reconstructive Surgery, Dept. of Developmental and Reconstructive Medicine, Nagasaki Univ., Graduate School of Biomedical and Sciences, Nagasaki (Japan); Ohtsuru, A [Takashi Nagai Memorial International Hibakusha Medical Center, Nagasaki Univ. Hospital, Nagasaki (Japan); Hirano, A [Div. of Plastic and Reconstructive Surgery, Dept. of Developmental and Reconstructive Medicine, Nagasaki Univ., Graduate School of Biomedical and Sciences, Nagasaki (Japan); Yamashita, S [Takashi Nagai Memorial International Hibakusha Medical Center, Nagasaki Univ. Hospital, Nagasaki (Japan); Dept. of Molecular Medicine, Atomic Bomb Disease Inst., Nagasaki Univ. School of Medicine, Nagasaki (Japan)

2012-07-01

Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6{+-}14.9 y (52-89 y), with mean radiation dose of 75.0{+-}35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6{+-}1.3 x 10{sup 7} cells were obtained. All cases healed uneventfully after 6.6{+-}3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9{+-}0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds. (authors)

A novel strategy of spine defect repair with a degradable bioactive scaffold preloaded with adipose-derived stromal cells.

Science.gov (United States)

Liang, Haixiang; Li, Xudong; Shimer, Adam L; Balian, Gary; Shen, Francis H

2014-03-01

Although the use of mesenchymal stem cells (MSC) with scaffolds for bone repair has been considered an effective method, the interactions between implanted materials and bone tissues have not been fully elucidated. At some specific sites, such as the vertebral body (VB) of the spine, the process of bone repair with implanted biomaterials is rarely reported. Recently, adipose tissue was found to be an alternative source of MSC besides bone marrow. However, the strategy of using adipose-derived stromal (ADS) cells with bioactive scaffold for the repair of spinal bone defects has seldom been studied. To use a sintered poly(lactide-co-glycolide) acid (PLGA) microspheres scaffold seeded with induced rat ADS cells to repair a bone defect of the VB in a rat model. Basic science and laboratory study. A sintered porous microspheres scaffold was manufactured by PLGA. ADS cells were isolated from Fischer 344 rats and then induced by osteogenic medium with growth and differentiation factor 5 (GDF5) in vitro. Before implantation, cells were cultured with inductive media for 2 weeks as a monolayer situation and 1 more week on a PLGA scaffold as a three-dimensional structure. These assembled bioactive scaffolds then were implanted in lumbar VB bone defects in Fischer 344 rats. The ex vivo differentiation of the cells was confirmed by von Kossa staining and real-time polymerase chain reaction. The performance of cells on the scaffold was detected by scanning electron microscopy and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. In vivo bone formation was quantitatively measured by computed tomography study. And the effect of tissue repair was also evaluated by histological studies. Proliferation and differentiation of cells were confirmed before in vivo implantation. Quantification of bone formation in vivo through serial three-dimensional computed tomography images revealed that the VB implanted with GDF5-induced cells

The biological activities of (1,3)-(1,6)-{beta}-d-glucan and porous electrospun PLGA membranes containing {beta}-glucan in human dermal fibroblasts and adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Woo, Yeon I; Park, Bong Joo; Kim, Hye-Lee; Lee, Mi Hee; Kim, Jungsung; Park, Jong-Chul [Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yang, Young-Il [Department of Pathology, School of Medicine, Paik Institute for Clinical Research, Inje University, 633-165 Gae-dong, Busan-jin-gu, Busan 614-735 (Korea, Republic of); Kim, Jung Koo [Department of Biomedical Engineering, College of Biomedical Science and Engineering, Inje University, Kimhae 621-749 (Korea, Republic of); Tsubaki, Kazufumi [R and D division, Asahi Denka Co. Ltd, 7-2-35 Higashi-ogu, Arakawa-ku, Tokyo 116-8554 (Japan); Han, Dong-Wook, E-mail: parkjc@yuhs.a [Department of Nanomedical Engineering, College of Nanoscience and Nanotechnology, Pusan National University, geumjeong-gu, Busan 609-735 (Korea, Republic of)

2010-08-01

In this study, we investigated the possible roles of (1,3)-(1,6)-{beta}-d-glucan ({beta}-glucan) and porous electrospun poly-lactide-co-glycolide (PLGA) membranes containing {beta}-glucan for skin wound healing, especially their effect on adult human dermal fibroblast (aHDF) and adipose tissue-derived stem cell (ADSC) activation, proliferation, migration, collagen gel contraction and biological safety tests of the prepared membrane. This study demonstrated that {beta}-glucan and porous PLGA membranes containing {beta}-glucan have enhanced the cellular responses, proliferation and migration, of aHDFs and ADSCs and the result of a collagen gel contraction assay also revealed that collagen gels contract strongly after 4 h post-gelation incubation with {beta}-glucan. Furthermore, we confirmed that porous PLGA membranes containing {beta}-glucan are biologically safe for wound healing study. These results indicate that the porous PLGA membranes containing {beta}-glucan interacted favorably with the membrane and the topical administration of {beta}-glucan was useful in promoting wound healing. Therefore, our study suggests that {beta}-glucan and porous PLGA membranes containing {beta}-glucan may be useful as a material for enhancing wound healing.

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

International Nuclear Information System (INIS)

Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

2015-01-01

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

Energy Technology Data Exchange (ETDEWEB)

Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

2015-08-14

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice

NARCIS (Netherlands)

Braster, Quinte; Silvestre Roig, Carlos; Hartwig, Helene; Beckers, Linda; den Toom, Myrthe; Döring, Yvonne; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

2016-01-01

Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of

Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

Directory of Open Access Journals (Sweden)

Hossein Rahavi

2015-01-01

Full Text Available Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs might be applied for type 1 diabetes mellitus (T1DM treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ- induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate and nonspecific (PHA triggers in a dose-dependent manner (P<0.05. Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P<0.05. Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P<0.05. In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

International Nuclear Information System (INIS)

Beane, Olivia S.; Fonseca, Vera C.; Darling, Eric M.

2014-01-01

In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

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Beane, Olivia S. [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Fonseca, Vera C. [Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Darling, Eric M., E-mail: Eric_Darling@brown.edu [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Department of Orthopaedics, Brown University, Providence, RI (United States); School of Engineering, Brown University, Providence, RI (United States)

2014-10-01

In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments

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P Karschnia

2018-05-01

Full Text Available The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO. Ad-MVF were isolated from green fluorescent protein (GFP+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

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Zhifa Wang

2016-02-01

Full Text Available To determine the effect of adipose-derived stem cells (ADSCs added to bone marrow-derived mesenchymal stem cell (MSC sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.

Comparison of Body Mass Index (BMI, Body Adiposity Index (BAI, Waist Circumference (WC, Waist-To-Hip Ratio (WHR and Waist-To-Height Ratio (WHtR as predictors of cardiovascular disease risk factors in an adult population in Singapore.

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Benjamin Chih Chiang Lam

Full Text Available Excess adiposity is associated with cardiovascular disease (CVD risk factors such as hypertension, diabetes mellitus and dyslipidemia. Amongst the various measures of adiposity, the best one to help predict these risk factors remains contentious. A novel index of adiposity, the Body Adiposity Index (BAI was proposed in 2011, and has not been extensively studied in all populations. Therefore, the purpose of this study is to compare the relationship between Body Mass Index (BMI, Waist Circumference (WC, Waist-to-Hip Ratio (WHR, Waist-to-Height Ratio (WHtR, Body Adiposity Index (BAI and CVD risk factors in the local adult population.This is a cross sectional study involving 1,891 subjects (Chinese 59.1% Malay 22.2%, Indian 18.7%, aged 21-74 years, based on an employee health screening (2012 undertaken at a hospital in Singapore. Anthropometric indices and CVD risk factor variables were measured, and Spearman correlation, Receiver Operating Characteristic (ROC curves and multiple logistic regressions were used. BAI consistently had the lower correlation, area under ROC and odd ratio values when compared with BMI, WC and WHtR, although differences were often small with overlapping 95% confidence intervals. After adjusting for BMI, BAI did not further increase the odds of CVD risk factors, unlike WC and WHtR (for all except hypertension and low high density lipoprotein cholesterol. When subjects with the various CVD risk factors were grouped according to established cut-offs, a BMI of ≥23.0 kg/m2 and/or WHtR ≥0.5 identified the highest proportion for all the CVD risk factors in both genders, even higher than a combination of BMI and WC.BAI may function as a measure of overall adiposity but it is unlikely to be better than BMI. A combination of BMI and WHtR could have the best clinical utility in identifying patients with CVD risk factors in an adult population in Singapore.

Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model.

Science.gov (United States)

Ha, Sungji; Park, Hyunjun; Mahmood, Usman; Ra, Jeong Chan; Suh, Yoo-Hun; Chang, Keun-A

2017-01-15

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display co-occurring repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on valproic acid (VPA)-induced autism model mice. Human ASCs were injected into the neonatal pups (P2 or P3) intraventricularly and then we evaluated major behavior symptoms of ASD. VPA-treated mice showed increased repetitive behaviors, decreased social interactions and increased anxiety but these autistic behaviors were ameliorated through transplantation of hASCs. In addition, hASCs transplantation restored the alteration of phosphatase and tensin homolog (PTEN) expression and p-AKT/AKT ratio in the brains of VPA-induced ASD model mice. The decreased level of vascular endothelial growth factor (VEGF) and interleukin 10 (IL-10) by VPA were rescued in the brains of the hASC-injected VPA mice. With these results, we experimentally found hASCs' therapeutic effects on autistic phenotypes in a ASD model mice for the first time. This animal model system can be used to elucidate further mechanisms of therapeutic effects of hASCs in ASD. Copyright © 2016 Elsevier B.V. All rights reserved.

Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes.

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Jayabalan, Nanthini; Nair, Soumyalekshmi; Nuzhat, Zarin; Rice, Gregory E; Zuñiga, Felipe A; Sobrevia, Luis; Leiva, Andrea; Sanhueza, Carlos; Gutiérrez, Jaime Agustín; Lappas, Martha; Freeman, Dilys Jane; Salomon, Carlos

2017-01-01

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body's major energy reservoir. The role of adipose tissue, however, is not restricted to a "bag of fat." The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue-derived

Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes

Directory of Open Access Journals (Sweden)

Nanthini Jayabalan

2017-09-01

adipose tissue-derived EVs and metabolic syndrome in obesity. In this review, we will discuss the changes in human placenta and adipose tissue in GDM and obesity and summarize the findings regarding the role of adipose tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the contribution of obesity to the development of GDM.

The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.

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Tove Fall

Full Text Available The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV for body mass index (BMI in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i rs9939609 and BMI (n  =  198,502, (ii rs9939609 and 24 traits, and (iii BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39 and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05. For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05. The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p  =  0

Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue

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Wang, Jun Kit; Luo, Baiwen; Guneta, Vipra [School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Li, Liang; Foo, Selin Ee Min [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Dai, Yun; Tan, Timothy Thatt Yang [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459 (Singapore); Tan, Nguan Soon [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore); KK Research Centre, KK Women' s and Children' s Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore); Choong, Cleo, E-mail: cleochoong@ntu.edu.sg [School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); KK Research Centre, KK Women' s and Children' s Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore); Wong, Marcus Thien Chong [Plastic, Reconstructive & Aesthetic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433 (Singapore)

2017-06-01

Adipose tissue is a rich source of extracellular matrix (ECM) material that can be isolated by delipidating and decellularizing the tissue. However, the current delipidation and decellularization methods either involve tedious and lengthy processes or require toxic chemicals, which may result in the elimination of vital proteins and growth factors found in the ECM. Hence, an alternative delipidation and decellularization method for adipose tissue was developed using supercritical carbon dioxide (SC-CO{sub 2}) that eliminates the need of any harsh chemicals and also reduces the amount of processing time required. The resultant SC-CO{sub 2}-treated ECM material showed an absence of nuclear content but the preservation of key proteins such as collagen Type I, collagen Type III, collagen Type IV, elastin, fibronectin and laminin. In addition, other biological factors such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also retained. Subsequently, the resulting SC-CO{sub 2}-treated ECM material was used as a bioactive coating on tissue culture plastic (TCP). Four different cell types including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells and human monocytic leukemia cells (THP-1) were used in this study to show that the SC-CO{sub 2}-treated ECM coating can be potentially used for various biomedical applications. The SC-CO{sub 2}-treated ECM material showed improved cell-material interactions for all cell types tested. In addition, in vitro scratch wound assay using HaCaT cells showed that the presence of SC-CO{sub 2}-treated ECM material enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1-derived macrophages showed that the SC-CO{sub 2}-treated ECM material did not evoke pro-inflammatory responses from the THP-1-derived macrophages. Overall

Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue.

Science.gov (United States)

Wang, Jun Kit; Luo, Baiwen; Guneta, Vipra; Li, Liang; Foo, Selin Ee Min; Dai, Yun; Tan, Timothy Thatt Yang; Tan, Nguan Soon; Choong, Cleo; Wong, Marcus Thien Chong

2017-06-01

Adipose tissue is a rich source of extracellular matrix (ECM) material that can be isolated by delipidating and decellularizing the tissue. However, the current delipidation and decellularization methods either involve tedious and lengthy processes or require toxic chemicals, which may result in the elimination of vital proteins and growth factors found in the ECM. Hence, an alternative delipidation and decellularization method for adipose tissue was developed using supercritical carbon dioxide (SC-CO 2 ) that eliminates the need of any harsh chemicals and also reduces the amount of processing time required. The resultant SC-CO 2 -treated ECM material showed an absence of nuclear content but the preservation of key proteins such as collagen Type I, collagen Type III, collagen Type IV, elastin, fibronectin and laminin. In addition, other biological factors such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also retained. Subsequently, the resulting SC-CO 2 -treated ECM material was used as a bioactive coating on tissue culture plastic (TCP). Four different cell types including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells and human monocytic leukemia cells (THP-1) were used in this study to show that the SC-CO 2 -treated ECM coating can be potentially used for various biomedical applications. The SC-CO 2 -treated ECM material showed improved cell-material interactions for all cell types tested. In addition, in vitro scratch wound assay using HaCaT cells showed that the presence of SC-CO 2 -treated ECM material enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1-derived macrophages showed that the SC-CO 2 -treated ECM material did not evoke pro-inflammatory responses from the THP-1-derived macrophages. Overall, this study shows the efficacy

Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue

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