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Sample records for adipose-tissue derived oral

  1. Adipose tissue-derived stem cells in oral mucosa tissue engineering ...

    African Journals Online (AJOL)

    Jane

    2011-10-10

    Oct 10, 2011 ... urethral reconstruction. Specifically, tissue-engineered oral mucosa holds great prospect for urethroplasty. Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue, that is, adipose tissue-derived stem cells (ADSCs), have been used in skin repair with satisfactory results.

  2. 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

  3. Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering.

    Science.gov (United States)

    Wang, Lina; Johnson, Joshua A; Zhang, Qixu; Beahm, Elisabeth K

    2013-11-01

    Repair of soft tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were proved by immunohistochemical analysis and DNA quantification. Scanning electron microscopic examination showed a three-dimensional nanofibrous architecture in hDAM. The hDAM included collagen, sulfated glycosaminoglycan, and vascular endothelial growth factor, but lacked major histocompatibility complex antigen I. hASC viability and proliferation on hDAM were proven in vitro. hDAM implanted subcutaneously in Fischer rats did not cause an immunogenic response, and it underwent remodeling, as indicated by host cell infiltration, neovascularization, and adipose tissue formation. Fresh fat grafts (Coleman technique) and engineered fat grafts (hDAM combined with hASCs) were implanted subcutaneously in nude rats. The implanted engineered fat grafts maintained their volume for 8 weeks, and the hASCs contributed to adipose tissue formation. In summary, the combination of hDAM and hASCs provides not only a clinically translatable platform for adipose tissue engineering, but also a vehicle for elucidating fat grafting mechanisms. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Adipose Tissue-Derived Stem Cells in Regenerative Medicine.

    Science.gov (United States)

    Frese, Laura; Dijkman, Petra E; Hoerstrup, Simon P

    2016-07-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted.

  5. Metabolically active human brown adipose tissue derived stem cells.

    Science.gov (United States)

    Silva, Francisco J; Holt, Dolly J; Vargas, Vanessa; Yockman, James; Boudina, Sihem; Atkinson, Donald; Grainger, David W; Revelo, Monica P; Sherman, Warren; Bull, David A; Patel, Amit N

    2014-02-01

    Brown adipose tissue (BAT) plays a key role in the evolutionarily conserved mechanisms underlying energy homeostasis in mammals. It is characterized by fat vacuoles 5-10 µm in diameter and expression of uncoupling protein one, central to the regulation of thermogenesis. In the human newborn, BAT depots are typically grouped around the vasculature and solid organs. These depots maintain body temperature during cold exposure by warming the blood before its distribution to the periphery. They also ensure an optimal temperature for biochemical reactions within solid organs. BAT had been thought to involute throughout childhood and adolescence. Recent studies, however, have confirmed the presence of active BAT in adult humans with depots residing in cervical, supraclavicular, mediastinal, paravertebral, and suprarenal regions. While human pluripotent stem cells have been differentiated into functional brown adipocytes in vitro and brown adipocyte progenitor cells have been identified in murine skeletal muscle and white adipose tissue, multipotent metabolically active BAT-derived stem cells from a single depot have not been identified in adult humans to date. Here, we demonstrate a clonogenic population of metabolically active BAT stem cells residing in adult humans that can: (a) be expanded in vitro; (b) exhibit multilineage differentiation potential; and (c) functionally differentiate into metabolically active brown adipocytes. Our study defines a new target stem cell population that can be activated to restore energy homeostasis in vivo for the treatment of obesity and related metabolic disorders. © 2013 AlphaMed Press.

  6. The effect of diabetes on the wound healing potential of adipose-tissue derived stem cells.

    Science.gov (United States)

    Kim, Sue Min; Kim, Yun Ho; Jun, Young Joon; Yoo, Gyeol; Rhie, Jong Won

    2016-03-01

    To investigate whether diabetes mellitus affects the wound-healing-promoting potential of adipose tissue-derived stem cells, we designed a wound-healing model using diabetic mice. We compared the degree of wound healing between wounds treated with normal adipose tissue-derived stem cells and wounds treated with diabetic adipose tissue-derived stem cells. We evaluated the wound-healing rate, the epithelial tongue distance, the area of granulation tissue, the number of capillary and the number of Ki-67-stained cells. The wound-healing rate was significantly higher in the normal adipose tissue-derived stem cells group than in the diabetic adipose tissue-derived stem cells group; it was also significantly higher in the normal adipose tissue-derived stem cells group than in the control group. Although the diabetic adipose tissue-derived stem cells group showed a better wound-healing rate than the control group, the difference was not statistically significant. Similar trends were observed for the other parameters examined: re-epithelisation and keratinocyte proliferation; granulation tissue formation; and dermal regeneration. However, with regard to the number of capillary, diabetic adipose tissue-derived stem cells retained their ability to promote neovasculisation and angiogenesis. These results reflect the general impairment of the therapeutic potential of diabetic adipose tissue-derived stem cells in vivo. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. 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.

  8. Characteristics of mouse adipose tissue-derived stem cells and therapeutic comparisons between syngeneic and allogeneic adipose tissue-derived stem cell transplantation in experimental autoimmune thyroiditis.

    Science.gov (United States)

    Choi, Eun Wha; Shin, Il Seob; Park, So Young; Yoon, Eun Ji; Kang, Sung Keun; Ra, Jeong Chan; Hong, Sung Hwa

    2014-01-01

    Previously, we found that the intravenous administration of human adipose tissue-derived mesenchymal stem cells was a promising therapeutic option for autoimmune thyroiditis even when the cells were transplanted into a xenogeneic model without an immunosuppressant. Therefore, we explored the comparison between the therapeutic effects of syngeneic and allogeneic adipose tissue-derived stem cells on an experimental autoimmune thyroiditis mouse model. Experimental autoimmune thyroiditis was induced in C57BL/6 mice by immunization with porcine thyroglobulin. Adipose tissue-derived stem cells derived from C57BL/6 mice (syngeneic) or BALB/c mice (allogeneic) or saline as a vehicle control were administered intravenously four times weekly. Blood and tissue samples were collected 1 week after the last transplantation. Adipose tissue-derived stem cells from mice were able to differentiate into multiple lineages in vitro; however, mouse adipose tissue-derived stem cells did not have immunophenotypes identical to those from humans. Syngeneic and allogeneic administrations of adipose tissue-derived stem cells reduced thyroglobulin autoantibodies and the inflammatory immune response, protected against lymphocyte infiltration into the thyroid, and restored the Th1/Th2 balance without any adverse effects. However, different humoral immune responses were observed for infused cells from different stem cell sources. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic and syngeneic administration, in that order. The stem cells were mostly found in the spleen, not the thyroid. This migration might be because the stem cells primarily function in systemic immune modulation, due to being given prior to disease induction. In this study, we confirmed that there were equal effects of adipose tissue-derived stem cells in treating autoimmune thyroiditis between syngeneic and allogeneic transplantations.

  9. Phenotypical and functional characterization of freshly isolated adipose tissue-derived stem cells

    NARCIS (Netherlands)

    Varma, Maikel J. Oedayrajsingh; Breuls, Roel G. M.; Schouten, Tabitha E.; Jurgens, Wouter J. F. M.; Bontkes, Hetty J.; Schuurhuis, Gerrit J.; van Ham, S. Marieke; van Milligen, Florine J.

    2007-01-01

    Adipose tissue contains a stromal vascular fraction (SVF) that is a rich source of adipose tissue-derived stem cells (ASCs). ASCs are multipotent and in vitro-expanded ASCs have the capacity to differentiate, into amongst others, adipocytes, chondrocytes, osteoblasts, and myocytes. For tissue

  10. Characterization of mesenchymal stem cells derived from equine adipose tissue

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    A.M. Carvalho

    2013-08-01

    Full Text Available Stem cell therapy has shown promising results in tendinitis and osteoarthritis in equine medicine. The purpose of this work was to characterize the adipose-derived mesenchymal stem cells (AdMSCs in horses through (1 the assessment of the capacity of progenitor cells to perform adipogenic, osteogenic and chondrogenic differentiation; and (2 flow cytometry analysis using the stemness related markers: CD44, CD90, CD105 and MHC Class II. Five mixed-breed horses, aged 2-4 years-old were used to collect adipose tissue from the base of the tail. After isolation and culture of AdMSCs, immunophenotypic characterization was performed through flow cytometry. There was a high expression of CD44, CD90 and CD105, and no expression of MHC Class II markers. The tri-lineage differentiation was confirmed by specific staining: adipogenic (Oil Red O, osteogenic (Alizarin Red, and chondrogenic (Alcian Blue. The equine AdMSCs are a promising type of adult progenitor cell for tissue engineering in veterinary medicine.

  11. Characterization of adipose tissue macrophages and adipose-derived stem cells in critical wounds

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    Bong-Sung Kim

    2017-01-01

    Full Text Available Background Subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers. Methods In the present study, we have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue. Subcutaneous adipose tissue adjacent to acutely inflamed wounds of 20 patients and 20 healthy subjects were harvested and underwent qPCR and flow cytometry analysis. Results Expression levels of the M1-specific markers CD80, iNOS, and IL-1b were significantly elevated in inflammatory adipose tissue when compared to healthy adipose tissue, whereas the M2-specific markers CD163 and TGF-β were decreased. By flow cytometry, a significant shift of adipose tissue macrophage populations towards the M1 phenotype was confirmed. Furthermore, a decrease in the mesenchymal stem cell markers CD29, CD34, and CD105 was observed whereas CD73 and CD90 remained unchanged. Discussion This is the first report describing the predominance of M1 adipose tissue macrophages and the reduction of stem cell marker expression in acutely inflamed, non-healing wounds.

  12. Characterization of adipose tissue macrophages and adipose-derived stem cells in critical wounds.

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    Kim, Bong-Sung; Tilstam, Pathricia V; Springenberg-Jung, Katrin; Boecker, Arne Hendrick; Schmitz, Corinna; Heinrichs, Daniel; Hwang, Soo Seok; Stromps, Jan Philipp; Ganse, Bergita; Kopp, Ruedger; Knobe, Matthias; Bernhagen, Juergen; Pallua, Norbert; Bucala, Richard

    2017-01-01

    Subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers. In the present study, we have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue. Subcutaneous adipose tissue adjacent to acutely inflamed wounds of 20 patients and 20 healthy subjects were harvested and underwent qPCR and flow cytometry analysis. Expression levels of the M1-specific markers CD80, iNOS, and IL-1b were significantly elevated in inflammatory adipose tissue when compared to healthy adipose tissue, whereas the M2-specific markers CD163 and TGF- β were decreased. By flow cytometry, a significant shift of adipose tissue macrophage populations towards the M1 phenotype was confirmed. Furthermore, a decrease in the mesenchymal stem cell markers CD29, CD34, and CD105 was observed whereas CD73 and CD90 remained unchanged. This is the first report describing the predominance of M1 adipose tissue macrophages and the reduction of stem cell marker expression in acutely inflamed, non-healing wounds.

  13. 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

  14. Mechanical Activation of Adipose Tissue and Derived Mesenchymal Stem Cells: Novel Anti-Inflammatory Properties.

    Science.gov (United States)

    Carelli, Stephana; Colli, Mattia; Vinci, Valeriano; Caviggioli, Fabio; Klinger, Marco; Gorio, Alfredo

    2018-01-16

    The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and CXCL8. Most of their production occurs in macrophages that act as scavengers of dying adipocytes. The application of an orbital mechanical force for 6-10 min at 97 g to the adipose tissue, lipoaspirated and treated according to Coleman procedures, abolishes the expression of TNF-α and stimulates the expression of the anti-inflammatory protein TNF-stimulated gene-6 (TSG-6). This protein had protective and anti-inflammatory effects when applied to animal models of rheumatic diseases. We examined biopsy, lipoaspirate, and mechanically activated fat and observed that in addition to the increased TSG-6, Sox2, Nanog, and Oct4 were also strongly augmented by mechanical activation, suggesting an effect on stromal cell stemness. Human adipose tissue-derived mesenchymal stem cells (hADSCs), produced from activated fat, grow and differentiate normally with proper cell surface markers and chromosomal integrity, but their anti-inflammatory action is far superior compared to those mesenchymal stem cells (MSCs) obtained from lipoaspirate. The expression and release of inflammatory cytokines from THP-1 cells was totally abolished in mechanically activated adipose tissue-derived hADSCs. In conclusion, we report that the orbital shaking of adipose tissue enhances its anti-inflammatory properties, and derived MSCs maintain such enhanced activity.

  15. 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

  16. Advantages of Sheep Infrapatellar Fat Pad Adipose Tissue Derived Stem Cells in Tissue Engineering.

    Science.gov (United States)

    Vahedi, Parviz; Soleimanirad, Jafar; Roshangar, Leila; Shafaei, Hajar; Jarolmasjed, Seyedhosein; Nozad Charoudeh, Hojjatollah

    2016-03-01

    The goal of this study has been to evaluate adipose tissue derived stem cells (ADSCs) from infrapatellar fat pad and characterize their cell surface markers using anti-human antibodies, as adipose tissue derived stem cells (ADSCs) have great potential for cellular therapies to restore injured tissues. Adipose tissue was obtained from infrapatellar fat pad of sheep. Surface markers evaluated by flow cytometry. In order to evaluate cell adhesion, the Polycaprolactone (PCL) was sterilized under Ultraviolet (UV) light and about 1×10(5) cells were seeded on PCL. Then, ASCs- PCL construct were evaluated by Scanning Electron Microscopy (Mira3 Te Scan, Czech Republic). We showed that adipose tissue derived stem cells (ADSCs) maintain their fibroblastic-like morphology during different subcultures and cell adhesion. They were positive for CD44 and CD90 markers and negative for CD31 and Cd45 markers by human antibodies. Our results suggest that ASCs surface markers can be characterized by anti-human antibodies in sheep. As stem cells, they can be used in tissue engineering.

  17. 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

  18. The impact of currently used oral antihyperglycemic drugs on dysfunctional adipose tissue

    Directory of Open Access Journals (Sweden)

    Tomić-Naglić Dragana

    2017-01-01

    Full Text Available Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.

  19. Hypoxia Enhances Differentiation of Adipose Tissue-Derived Stem Cells toward the Smooth Muscle Phenotype.

    Science.gov (United States)

    Wang, Fang; Zachar, Vladimir; Pennisi, Cristian Pablo; Fink, Trine; Maeda, Yasuko; Emmersen, Jeppe

    2018-02-08

    Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. The specific contractile properties of cells were verified with both a single cell contraction assay and a gel contraction assay. Five percent oxygen concentration significantly increased the expression levels of α-smooth muscle actin, calponin, and myosin heavy chain in adipose-derived stem cell cultures after 2 weeks of induction ( p Cells differentiated in 5% oxygen conditions showed greater contraction effect ( p cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

  20. Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues.

    Science.gov (United States)

    Chen, Yu-Jen; Liu, Hui-Yu; Chang, Yun-Tsui; Cheng, Ying-Hung; Mersmann, Harry J; Kuo, Wen-Hung; Ding, Shih-Torng

    2016-03-31

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. The dorsal white fat depot of porcine subcutaneous adipose tissues is sliced, minced and collagenase digested. These pADSC exhibit strong potential to differentiate into adipocytes. Moreover, the pADSC also possess multipotency, assessed by selective stem cell markers, to differentiate into various mesenchymal cell types including adipocytes, osteocytes, and chondrocytes. These pADSC can be used for clarification of molecular switches in regulating classical adipocyte differentiation or in direction to other mesenchymal cell types of mesodermal origin. Furthermore, extended lineages into cells of ectodermal and endodermal origin have recently been achieved. Therefore, pADSC derived in this protocol provide an abundant and assessable source of adult mesenchymal stem cells with full multipotency for studying adipose development and application to tissue engineering of regenerative medicine.

  1. Regulation of visceral adipose tissue-derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue.

    Science.gov (United States)

    González, C R; Caminos, J E; Vázquez, M J; Garcés, M F; Cepeda, L A; Angel, A; González, A C; García-Rendueles, M E; Sangiao-Alvarellos, S; López, M; Bravo, S B; Nogueiras, R; Diéguez, C

    2009-07-15

    Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a recently discovered adipocytokine mainly secreted from visceral adipose tissue, which plays a main role in insulin sensitivity. In this study, we have investigated the regulation of vaspin gene expression in rat white adipose tissue (WAT) in different physiological (nutritional status, pregnancy, age and gender) and pathophysiological (gonadectomy, thyroid status and growth hormone deficiency) settings known to be associated with energy homeostasis and alterations in insulin sensitivity. We have determined vaspin gene expression by real-time PCR. Vaspin was decreased after fasting and its levels were partially recovered after leptin treatment. Chronic treatment with metformin increased vaspin gene expression. Vaspin mRNA expression reached the highest peak at 45 days in both sexes after birth and its expression was higher in females than males, but its levels did not change throughout pregnancy. Finally, decreased levels of growth hormone and thyroid hormones suppressed vaspin expression. These findings suggest that WAT vaspin mRNA expression is regulated by nutritional status, and leptin seems to be the nutrient signal responsible for those changes. Vaspin is influenced by age and gender, and its expression is increased after treatment with insulin sensitizers. Finally, alterations in pituitary functions modify vaspin levels. Understanding the molecular mechanisms regulating vaspin will provide new insights into the pathogenesis of the metabolic syndrome.

  2. 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.

  3. 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

  4. 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.

  5. Comparison of chondrocytes produced from adipose tissue-derived stem cells and cartilage tissue.

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    Meric, Aysenur; Yenigun, Alper; Yenigun, Vildan Betul; Dogan, Remzi; Ozturan, Orhan

    2013-05-01

    Spontaneous cartilage regeneration is poor after a cartilage defect occurs by trauma, surgical, and other reasons. Importance of producing chondrocytes from stem cells and using tissues to repair a defect is getting popular. The aim of this study was to compare the effects of injectable cartilage produced by chondrocytes differentiated from adipose tissue-derived mesenchymal stem cells and chondrocyte cells isolated directly from cartilage tissue. Mesenchymal stem cells were isolated from rat adipose tissue and characterized by cell-surface markers. Then, they were differentiated to chondrocyte cells. The function of differentiated chondrocyte cells was compared with chondrocyte cells directly isolated from cartilage tissue in terms of collagen and glycosaminoglycan secretion. Then, both chondrocyte cell types were injected to rats' left ears in liquid and gel form, and histologic evaluation was done 3 weeks after the injection. Adipose-derived stem cells were strongly positive for the CD44 and CD73 mesenchymal markers. Differentiated chondrocyte cells and chondrocyte cells directly isolated from cartilage tissue had relative collagen and glycosaminoglycan secretion results. However, histologic evaluations did not show any cartilage formation after both chondrocyte cell types were injected to rats. Strong CD44- and CD73-positive expression indicated that adipose-derived cells had the stem cell characters. Collagen and glycosaminoglycan secretion results demonstrated that adipose-derived stem cells were successfully differentiated to chondrocyte cells.

  6. Adipose Tissue-Derived Stromal Cells Inhibit TGF-beta 1-Induced Differentiation of Human Dermal Fibroblasts and Keloid Scar-Derived Fibroblasts in a Paracrine Fashion

    NARCIS (Netherlands)

    Spiekman, Maroesjka; Przybyt, Ewa; Plantinga, Josee A.; Gibbs, Susan; van der Lei, Berend; Harmsen, Martin C.

    2014-01-01

    Background: Adipose tissue-derived stromal cells augment wound healing and skin regeneration. It is unknown whether and how they can also influence dermal scarring. The authors hypothesized that adipose tissue-derived stromal cells inhibit adverse differentiation of dermal fibroblasts induced by the

  7. Oral administration of visceral adipose tissue antigens ameliorates metabolic disorders in mice and elevates visceral adipose tissue-resident CD4+CD25+Foxp3+regulatory T cells.

    Science.gov (United States)

    Chen, Xiangyu; Zhang, Dali; Chen, Xiaoling; Meng, Gang; Zheng, Qian; Mai, Wenli; Wu, Yuzhang; Ye, Lilin; Wang, Li

    2017-08-16

    Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4 + Foxp3 + Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders. Oral tolerance strategy may modulate inflammatory response to autoantigens by several mechanisms including induction of autoantigen-specific Tregs. Here, we explored the effects and cellular mechanism of oral administration of VAT pooled antigens on high-fat diet (HFD)-induced metabolic disorders in mice. Indeed, we found that oral treatment of VAT mixture antigens effectively inhibited gain in body weight and fat mass, ameliorated serum lipid parameters, and improved insulin sensitivity in HFD mice. This strategy was shown to significantly restore HFD-induced decrease of VAT-resident Tregs, accompanied by a hampered M2-type to M1-type macrophages phenotypic switch as well as decreased CD8 + T cells infiltration in VAT. Thus, oral administration of VAT antigens may be a novel and safe strategy against obesity and its related metabolic disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells.

    Science.gov (United States)

    Yang, Jessica P; Anderson, Amy E; McCartney, Annemarie; Ory, Xavier; Ma, Garret; Pappalardo, Elisa; Bader, Joel; Elisseeff, Jennifer H

    2017-04-01

    Brown adipose tissue (BAT) has a unique capacity to expend calories by decoupling energy expenditure from ATP production, therefore BAT could realize therapeutic potential to treat metabolic diseases such as obesity and type 2 diabetes. Recent studies have investigated markers and function of native BAT, however, successful therapies will rely on methods that supplement the small existing pool of brown adipocytes in adult humans. In this study, we engineered BAT from both human and rat adipose precursors and determined whether these ex vivo constructs could mimic in vivo tissue form and metabolic function. Adipose-derived stem cells (ASCs) were isolated from several sources, human white adipose tissue (WAT), rat WAT, and rat BAT, then differentiated toward both white and brown adipogenic lineages in two-dimensional and three-dimensional (3D) culture conditions. ASCs derived from WAT were successfully differentiated in 3D poly(ethylene glycol) hydrogels into mature adipocytes with BAT phenotype and function, including high uncoupling protein 1 (UCP1) mRNA and protein expression and increased metabolic activity (basal oxygen consumption, proton leak, and maximum respiration). By utilizing this "browning" process, the abundant and accessible WAT stem cell population can be engineered into 3D tissue constructs with the metabolic capacity of native BAT, ultimately for therapeutic intervention in vivo and as a tool for studying BAT and its metabolic properties.

  9. Intracutaneously injected human adipose tissue-derived stem cells in a mouse model stay at the site of injection.

    Science.gov (United States)

    Koellensperger, E; Lampe, K; Beierfuss, A; Gramley, F; Germann, G; Leimer, U

    2014-06-01

    The aim of this study was to evaluate the local behavior of intracutaneously injected human mesenchymal stem cells from adipose tissue and to determine the safety of a cell-based cutaneous therapy in an animal model.Human mesenchymal stem cells from adipose tissue were labeled with red fluorochrome and were injected intradermally in the paravertebral area in immunodeficient BalbC/nude mice (n = 21). As a control, cell culturemedium was injected in the same fashion on the contralateral paravertebral side. Four weeks, 6 months, and 12 months after the injection, seven mice were examined. In addition to the injected areas, the lungs, kidneys,spleens, and brains were excised and processed for histological evaluation. Serial sections of all the tissues excised were evaluated for adipose tissue-derived stem cells by means of emerging red fluorescent signals.The injected stem cells could be detected throughout the follow-up period of 1-year at the injection site within the dermal and subcutaneous layers. Bar these areas, adipose tissue-derived stem cells were not found in any otherexamined tissue at any point in time. The adipose tissue-derived stem cells showed a slow transition to deeper subcutaneous adipose tissue layers and, in part, a differentiation into adipocytes. No ulceration, inflammation, ortumor induction could be detected.The present study shows that intracutaneously injected human mesenchymal stem cells from adipose tissue stay at the site of injection, survive in vivo for up to 1-year, and partly differentiate into adipocytes. This is a new andvery important finding needed to safely apply therapies based on such stem cells in fat transplants in regenerative medicine. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Adipose-derived stem cell differentiation as a basic tool for vascularized adipose tissue engineering.

    Science.gov (United States)

    Volz, Ann-Cathrin; Huber, Birgit; Kluger, Petra J

    2016-01-01

    The development of in vitro adipose tissue constructs is highly desired to cope with the increased demand for substitutes to replace damaged soft tissue after high graded burns, deformities or tumor removal. To achieve clinically relevant dimensions, vascularization of soft tissue constructs becomes inevitable but still poses a challenge. Adipose-derived stem cells (ASCs) represent a promising cell source for the setup of vascularized fatty tissue constructs as they can be differentiated into adipocytes and endothelial cells in vitro and are thereby available in sufficiently high cell numbers. This review summarizes the currently known characteristics of ASCs and achievements in adipogenic and endothelial differentiation in vitro. Further, the interdependency of adipogenesis and angiogenesis based on the crosstalk of endothelial cells, stem cells and adipocytes is addressed at the molecular level. Finally, achievements and limitations of current co-culture conditions for the construction of vascularized adipose tissue are evaluated. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  11. CXCL5 secreted from adipose tissue-derived stem cells promotes cancer cell proliferation.

    Science.gov (United States)

    Zhao, Yuying; Zhang, Xiaosan; Zhao, Hong; Wang, Jingxuan; Zhang, Qingyuan

    2018-02-01

    Accumulating data suggest that adipose tissue facilitates breast tumor initiation and progression through paracrine and endocrine pathways, and that adipose tissue-derived stem cell (ASC) is likely the major cell type responsible for tumorigenesis and tumor development. However, it remains unknown how ASCs exert their effects. In the present study, in cultured breast cancer cell lines, including estrogen receptor (ER)-positive MCF-7 cells and ER-negative MDA-MB-231 cells, the effects on tumor proliferation of isolated ASCs from human breasts were examined. The expression of 174 cytokines was additionally identified in this medium. With an anti-human C-X-C motif ligand 5 (CXCL5) monoclonal antibody, the effects of neutralization of CXCL5 on the actions of ASCs in a co-culture medium of ASCs and tumor cells were studied The results demonstrated that ASCs significantly increased the number of breast cancer cells compared with controls. Similarly, the co-culture medium of ASCs with breast cancer cells exhibited potent effects on tumor cell proliferation. In the co-culture medium of ASCs with breast cancer cells, CXCL5 levels were significantly increased. In addition, depletion of CXCL5 with its specific antibody in ASC-conditioned medium blocked the stimulatory effect of ASCs on the proliferation of breast cancer cells. To the best of our knowledge, these results indicate for the first time that ASC-secreted CXCL5 is a key factor promoting breast tumor cell proliferation.

  12. Autologous rabbit adipose tissue-derived mesenchymal stromal cells for the treatment of bone injuries with distraction osteogenesis.

    Science.gov (United States)

    Sunay, Ozgur; Can, Geylani; Cakir, Zeynep; Denek, Ziya; Kozanoglu, Ilknur; Erbil, Guven; Yilmaz, Mustafa; Baran, Yusuf

    2013-06-01

    Adipose tissue-derived mesenchymal stromal cells (MSCs) have a higher capacity for proliferation and differentiation compared with other cell lineages. Although distraction osteogenesis is the most important therapy for treating bone defects, this treatment is restricted in many situations. The aim of this study was to examine the therapeutic potential of adipose tissue-derived MSCs and osteoblasts differentiated from adipose tissue-derived MSCs in the treatment of bone defects. Bone defects were produced in the tibias of New Zealand rabbits that had previously undergone adipose tissue extraction. Tibial osteotomy was performed, and a distractor was placed on the right leg of the rabbits. The rabbits were placed in control (group I), stem cell (group II) and osteoblast-differentiated stem cell (group III) treatment groups. The rabbits were sacrificed, and the defect area was evaluated by radiologic, biomechanical and histopathologic tests to examine the therapeutic effects of adipose tissue-derived MSCs. Radiologic analyses revealed that callus density and the ossification rate increased in group III compared with group I and group II. In biomechanical tests, the highest ossification rate was observed in group III. Histopathologic studies showed that the quality of newly formed bone and the number of cells active in bone formation were significantly higher in group III rabbits compared with group I and group II rabbits. These data reveal that osteoblasts differentiated from adipose tissue-derived MSCs shorten the consolidation period of distraction osteogenesis. Stem cells could be used as an effective treatment for bone defects. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. 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

  14. Adipose tissue engineering using adipose-derived stem cells enclosed within an injectable carboxymethylcellulose-based hydrogel.

    Science.gov (United States)

    Ogushi, Yuko; Sakai, Shinji; Kawakami, Koei

    2013-11-01

    In situ gelation of an aqueous solution of carboxymethylcellulose derivative bearing phenolic hydroxyl groups (CMC-Ph) that contained suspended adipose-derived stem cells (ASCs) was studied in vitro and in vivo for evaluating feasibility in adipose tissue-engineering strategies. The rat ASCs that were enclosed in the CMC-Ph gels through a horseradish peroxidase-catalysed reaction showed 92.8% viability, good proliferation and adipogenic differentiation in vitro. Ten weeks after the subcutaneous injection of ASCs-suspending CMC-Ph for in situ gelation, clearly visible new vascularized adipose tissue formed at the injection site. The number of blood vessels and the area occupied by adipose tissues were five and eight times larger, respectively, than those found in the implanted acellular gel. The adipogenesis and neovascularization were further enhanced by incorporation of fibroblast growth factor into the CMC-Ph gel containing ASCs. Copyright © 2012 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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

  16. Isolation of autologous adipose tissue-derived mesenchymal stem cells for bone repair.

    Science.gov (United States)

    Raposio, E; Bonomini, S; Calderazzi, F

    2016-11-01

    Adipose tissue represents an abundant and accessible source of adult stem cells that can differentiate into cells and tissues of mesodermal origin, including osteogenic cells. This paper describes the procedure to obtain a 5-cm 3 saline sample, containing the adipose-derived stem cells (ASCs) pellet, starting from lipoaspirate obtained from a conventional abdominal liposuction. A mean of 2.5×10 6  cells is isolated for each procedure; 35% (875000) of these are CD34+/CD45- cells, which express a subset of both positive (CD10, CD13, CD44, CD59, CD73, CD90, HLAABC) and negative (CD33, CD39, CD102, CD106, CD146, HLADR) cell-associated surface antigens, characterizing them as ASCs. This procedure is easy, effective, economic and safe. It allows the harvesting of a significant number of ASCs that are ready for one-step bony regenerative surgical procedures. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Effect of oral oleoyl-estrone on adipose tissue composition in male rats.

    Science.gov (United States)

    Remesar, X; Fernández-López, J A; Blay, M T; Savall, P; Salas, A; Díaz-Silva, M; Esteve, M; Grasa, M M; Alemany, M

    2002-08-01

    To determine whether the oral administration of oleoyl-estrone has similar mass-decreasing effects on the main different sites of white adipose tissue (WAT). Adult male Zucker lean rats were given a daily oral gavage of oleoyl-estrone (OE, 10 micromol/kg) in 0.2 ml of sunflower oil for 10 days, and were compared with controls receiving only the oil. The mass of the main WAT sites: subcutaneous, epididymal, mesenteric, retroperitoneal, gluteal, perirenal and interscapular, as well as perirenal and interscapular brown adipose tissue (BAT), were dissected and studied. The tissue weight, DNA, protein, lipid and total cholesterol content, together with the levels of leptin and acyl-estrone in the larger WAT and BAT masses, were measured. The weights of WAT depots were correlated with body weight but those of BAT were not. Cell size was maximal for epididymal and mesenteric and minimal for subcutaneous and retroperitoneal WAT and BAT. Differences were detected in DNA, and in protein and lipid content between distinct WAT sites. OE treatment tended to decrease cell number and cell size in WAT; only small differences in composition were found between WAT locations inside the visceral cavity and those outside. Decreases in lipid content were maximal in mesenteric fat. Leptin and acyl-estrone content were fairly uniform at the different WAT sites, except for high concentrations in gluteal WAT. OE induced a greater decrease in leptin and acyl-estrone than in DNA and lipids; changes in these hormones were fairly parallel in all sites. In general, the differences in composition between visceral and peripheral subcutaneous WAT and their responses to OE were less marked than the individual differences observed between specific sites, regardless of location. WAT sites are fairly diverse in composition, but their response to OE treatment was uniform. OE decreased the weight of WAT through reduction of both cell numbers and size; but did not change the mass or composition of BAT

  18. 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.

  19. The adipose tissue-derived stromal vascular fraction cells from lipedema patients: Are they different?

    Science.gov (United States)

    Priglinger, Eleni; Wurzer, Christoph; Steffenhagen, Carolin; Maier, Julia; Hofer, Victoria; Peterbauer, Anja; Nuernberger, Sylvia; Redl, Heinz; Wolbank, Susanne; Sandhofer, Matthias

    2017-07-01

    Lipedema is a hormone-related disease of women characterized by enlargement of the extremities caused by subcutaneous deposition of adipose tissue. In healthy patients application of autologous adipose tissue-derived cells has shown great potential in several clinical studies for engrafting of soft tissue reconstruction in recent decades. The majority of these studies have used the stromal vascular fraction (SVF), a heterogeneous cell population containing adipose-derived stromal/stem cells (ASC), among others. Because cell identity and regenerative properties might be affected by the health condition of patients, we characterized the SVF cells of 30 lipedema patients in comparison to 22 healthy patients. SVF cells were analyzed regarding cell yield, viability, adenosine triphosphate content, colony forming units and proliferative capacity, as well as surface marker profile and differentiation potential in vitro. Our results demonstrated a significantly enhanced SVF cell yield isolated from lipedema compared with healthy patients. In contrast, the adipogenic differentiation potential of SVF cells isolated from lipedema patients was significantly reduced compared with healthy patients. Interestingly, expression of the mesenchymal marker CD90 and the endothelial/pericytic marker CD146 was significantly enhanced when isolated from lipedema patients. The enhanced number of CD90 + and CD146 + cells could explain the increased cell yield because the other tested surface marker were not reduced in lipedema patients. Because the cellular mechanism and composition in lipedema is largely unknown, our findings might contribute to a better understanding of its etiology. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. Ultrasound -Assisted Gene Transfer to Adipose Tissue-Derived Stem/Progenitor Cells (ASCs)

    Science.gov (United States)

    Miyamoto, Yoshitaka; Ueno, Hitomi; Hokari, Rei; Yuan, Wenji; Kuno, Shuichi; Kakimoto, Takashi; Enosawa, Shin; Negishi, Yoichi; Yoshinaka, Kiyoshi; Matsumoto, Yoichiro; Chiba, Toshio; Hayashi, Shuji

    2011-09-01

    In recent years, multilineage adipose tissue-derived stem cells (ASCs) have become increasingly attractive as a promising source for cell transplantation and regenerative medicine. Particular interest has been expressed in the potential to make tissue stem cells, such as ASCs and marrow stromal cells (MSCs), differentiate by gene transfection. Gene transfection using highly efficient viral vectors such as adeno- and sendai viruses have been developed for this purpose. Sonoporation, or ultrasound (US)-assisted gene transfer, is an alternative gene manipulation technique which employs the creation of a jet stream by ultrasonic microbubble cavitation. Sonoporation using non-viral vectors is expected to be a much safer, although less efficient, tool for prospective clinical gene therapy. In this report, we assessed the efficacy of the sonoporation technique for gene transfer to ASCs. We isolated and cultured adipocyets from mouse adipose tissue. ASCs that have the potential to differentiate with transformation into adipocytes or osteoblasts were obtained. Using the US-assisted system, plasmid DNA containing beta-galactosidase (beta-Gal) and green fluorescent protein (GFP) genes were transferred to the ASCs. For this purpose, a Sonopore 4000 (NEPAGENE Co.) and a Sonazoid (Daiichi Sankyo Co.) instrument were used in combination. ASCs were subjected to US (3.1 MHz, 50% duty cycle, burst rate 2.0 Hz, intensity 1.2 W/cm2, exposure time 30 sec). We observed that the gene was more efficiently transferred with increased concentrations of plasmid DNA (5-150 μg/mL). However, further optimization of the US parameters is required, as the gene transfer efficiency was still relatively low. In conclusion, we herein demonstrate that a gene can be transferred to ASCs using our US-assisted system. In regenerative medicine, this system might resolve the current issues surrounding the use of viral vectors for gene transfer.

  1. 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.

  2. 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...

  3. 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

  4. 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

  5. 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

  6. New adipose tissue formation by human adipose-derived stem cells with hyaluronic acid gel in immunodeficient mice.

    Science.gov (United States)

    Huang, Shu-Hung; Lin, Yun-Nan; Lee, Su-Shin; Chai, Chee-Yin; Chang, Hsueh-Wei; Lin, Tsai-Ming; Lai, Chung-Sheng; Lin, Sin-Daw

    2015-01-01

    Currently available injectable fillers have demonstrated limited durability. This report proposes the in vitro culture of human adipose-derived stem cells (hASCs) on hyaluronic acid (HA) gel for in vivo growth of de novo adipose tissue. For in vitro studies, hASCs were isolated from human adipose tissue and were confirmed by multi-lineage differentiation and flow cytometry. hASCs were cultured on HA gel. The effectiveness of cell attachment and proliferation on HA gel was surveyed by inverted light microscopy. For in vivo studies, HA gel containing hASCs, hASCs without HA gel, HA gel alone were allocated and subcutaneously injected into the subcutaneous pocket in the back of nude mice (n=6) in each group. At eight weeks post-injection, the implants were harvested for histological examination by hematoxylin and eosin (H&E) stain, Oil-Red O stain and immunohistochemical staining. The human-specific Alu gene was examined. hASCs were well attachment and proliferation on the HA gel. In vivo grafts showed well-organized new adipose tissue on the HA gel by histologic examination and Oil-Red O stain. Analysis of neo-adipose tissues by PCR revealed the presence of the Alu gene. This study demonstrated not only the successful culture of hASCs on HA gel, but also their full proliferation and differentiation into adipose tissue. The efficacy of injected filler could be permanent since the reduction of the volume of the HA gel after bioabsorption could be replaced by new adipose tissue generated by hASCs. This is a promising approach for developing long lasting soft tissue filler.

  7. Comparison of human adipose-derived stem cells isolated from subcutaneous, omental, and intrathoracic adipose tissue depots for regenerative applications.

    Science.gov (United States)

    Russo, Valerio; Yu, Claire; Belliveau, Paul; Hamilton, Andrew; Flynn, Lauren E

    2014-02-01

    Adipose tissue is an abundant source of multipotent progenitor cells that have shown promise in regenerative medicine. In humans, fat is primarily distributed in the subcutaneous and visceral depots, which have varying biochemical and functional properties. In most studies to date, subcutaneous adipose tissue has been investigated as the adipose-derived stem cell (ASC) source. In this study, we sought to develop a broader understanding of the influence of specific adipose tissue depots on the isolated ASC populations through a systematic comparison of donor-matched abdominal subcutaneous fat and omentum, and donor-matched pericardial adipose tissue and thymic remnant samples. We found depot-dependent and donor-dependent variability in the yield, viability, immunophenotype, clonogenic potential, doubling time, and adipogenic and osteogenic differentiation capacities of the ASC populations. More specifically, ASCs isolated from both intrathoracic depots had a longer average doubling time and a significantly higher proportion of CD34(+) cells at passage 2, as compared with cells isolated from subcutaneous fat or the omentum. Furthermore, ASCs from subcutaneous and pericardial adipose tissue demonstrated enhanced adipogenic differentiation capacity, whereas ASCs isolated from the omentum displayed the highest levels of osteogenic markers in culture. Through cell culture analysis under hypoxic (5% O(2)) conditions, oxygen tension was shown to be a key mediator of colony-forming unit-fibroblast number and osteogenesis for all depots. Overall, our results suggest that depot selection is an important factor to consider when applying ASCs in tissue-specific cell-based regenerative therapies, and also highlight pericardial adipose tissue as a potential new ASC source.

  8. Leukocyte-Reduced Platelet-Rich Plasma Alters Protein Expression of Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Loibl, Markus; Lang, Siegmund; Hanke, Alexander; Herrmann, Marietta; Huber, Michaela; Brockhoff, Gero; Klein, Silvan; Nerlich, Michael; Angele, Peter; Prantl, Lukas; Gehmert, Sebastian

    2016-08-01

    Application of platelet-rich plasma and stem cells has become important in regenerative medicine. Recent literature supports the use of platelet-rich plasma as a cell culture media supplement to stimulate proliferation of adipose tissue-derived mesenchymal stem cells. The underlying mechanism of proliferation stimulation by platelet-rich plasma has not been investigated so far. Adipose tissue-derived mesenchymal stem cells were cultured in α-minimal essential medium supplemented with platelet-rich plasma or fetal calf serum. Cell proliferation was assessed with cell cycle kinetics using flow cytometric analyses after 48 hours. Differences in proteome expression of the adipose tissue-derived mesenchymal stem cells were analyzed using a reverse-phase protein array to quantify 214 proteins. Complementary Ingenuity Pathways Analysis and gene set enrichment analysis were performed using protein data, and confirmed by Western blot analysis. A higher percentage of adipose tissue-derived mesenchymal stem cells in the S phase in the presence of platelet-rich plasma advocates the proliferation stimulation. Ingenuity Pathways Analysis and gene set enrichment analysis confirm the involvement of the selected proteins in the process of cell growth and proliferation. Ingenuity Pathways Analysis revealed a participation in the top-ranked canonical pathways PI3K/AKT, PTEN, ILK, and IGF-1. Gene set enrichment analysis identified the authors' protein set as being part of significantly regulated protein sets with the focus on cell cycle, metabolism, and the Kyoto Encyclopedia of Genes and Genomes transforming growth factor-β signaling pathway. The present study provides evidence that platelet-rich plasma stimulates proliferation and induces a unique change in the proteomic profile of adipose tissue-derived mesenchymal stem cells. The interpretation of altered expression of regulatory proteins represents a step forward toward achieving good manufacturing practice-compliant criteria

  9. 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

  10. Matrix directed adipogenesis and neurogenesis of mesenchymal stem cells derived from adipose tissue and bone marrow.

    Science.gov (United States)

    Lee, Junmin; Abdeen, Amr A; Tang, Xin; Saif, Taher A; Kilian, Kristopher A

    2016-09-15

    Mesenchymal stem cells (MSCs) can differentiate into multiple lineages through guidance from the biophysical and biochemical properties of the extracellular matrix. In this work we conduct a combinatorial study of matrix properties that influence adipogenesis and neurogenesis including: adhesion proteins, stiffness, and cell geometry, for mesenchymal stem cells derived from adipose tissue (AT-MSCs) and bone marrow (BM-MSCs). We uncover distinct differences in integrin expression, the magnitude of traction stress, and lineage specification to adipocytes and neuron-like cells between cell sources. In the absence of media supplements, adipogenesis in AT-MSCs is not significantly influenced by matrix properties, while the converse is true in BM-MSCs. Both cell types show changes in the expression of neurogenesis markers as matrix cues are varied. When cultured on laminin conjugated microislands of the same adhesive area, BM-MSCs display elevated adipogenesis markers, while AT-MSCs display elevated neurogenesis markers; integrin analysis suggests neurogenesis in AT-MSCs is guided by adhesion through integrin αvβ3. Overall, the properties of the extracellular matrix guides MSC adhesion and lineage specification to different degrees and outcomes, in spite of their similarities in general characteristics. This work will help guide the selection of MSCs and matrix components for applications where high fidelity of differentiation outcome is desired. Mesenchymal stem cells (MSCs) are an attractive cell type for stem cell therapies; however, in order for these cells to be useful in medicine, we need to understand how they respond to the physical and chemical environments of tissue. Here, we explore how two promising sources of MSCs-those derived from bone marrow and from adipose tissue-respond to the compliance and composition of tissue using model extracellular matrices. Our results demonstrate a source-specific propensity to undergo adipogenesis and neurogenesis, and

  11. Adipose Derived-Mesenchymal Stem Cells Viability and Differentiating Features for Orthopaedic Reparative Applications: Banking of Adipose Tissue

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    Ilaria Roato

    2016-01-01

    Full Text Available Osteoarthritis is characterized by loss of articular cartilage also due to reduced chondrogenic activity of mesenchymal stem cells (MSCs from patients. Adipose tissue is an attractive source of MSCs (ATD-MSCs, representing an effective tool for reparative medicine, particularly for treatment of osteoarthritis, due to their chondrogenic and osteogenic differentiation capability. The treatment of symptomatic knee arthritis with ATD-MSCs proved effective with a single infusion, but multiple infusions could be also more efficacious. Here we studied some crucial aspects of adipose tissue banking procedures, evaluating ATD-MSCs viability, and differentiation capability after cryopreservation, to guarantee the quality of the tissue for multiple infusions. We reported that the presence of local anesthetic during lipoaspiration negatively affects cell viability of cryopreserved adipose tissue and cell growth of ATD-MSCs in culture. We observed that DMSO guarantees a faster growth of ATD-MSCs in culture than trehalose. At last, ATD-MSCs derived from fresh and cryopreserved samples at −80°C and −196°C showed viability and differentiation ability comparable to fresh samples. These data indicate that cryopreservation of adipose tissue at −80°C and −196°C is equivalent and preserves the content of ATD-MSCs in Stromal Vascular Fraction (SVF, guaranteeing the differentiation ability of ATD-MSCs.

  12. 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

  13. 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.

  14. Enzymatically crosslinked gelatin hydrogel promotes the proliferation of adipose tissue-derived stromal cells

    Directory of Open Access Journals (Sweden)

    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.

  15. The potentials of human adipose tissue derived mesenchymal stem cells in targeted therapy of experimental glioma

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    FAN Cun-gang

    2012-12-01

    Full Text Available Glioblastoma is the most common primary malignant brain tumor in adults. With current standard therapy which includes extensive microsurgical resection along with concurrent chemoradiotherapy and adjuvant temozolomide (TMZ, the median survival of glioblastoma patients is only 14.60 months nowadays. Recent studies demonstrated that human adipose tissue derived mesenchymal stem cells (hAT-MSCs possessed the glioma-trophic migratory capacity. The engineered hAT-MSCs expressing herpes simplex virus-thymidine kinase (HSV-tk, yeast cytosine deaminase::uracil phosphoribosyltransferase (CDy:: UPRT, and rabbit carboxylesterase (rCE could exert inhibitory effects on glioma when combined with prodrugs, such as ganciclovir (GCV, 5-fluorocytosine (5-FC and irinotecan (CPT-11, respectively. hAT-MSCs carrying the oncolytic virus or expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL also could inhibit the growth of glioma. This paper summarizes the recent progress in this field to pave the way for hAT-MSCs based targeted therapy of glioma in future.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-01-01

    Full Text Available Osteoarthritis (OA is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs in the form of stromal vascular fraction (SVF may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP, have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.

  18. Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of Ovarian Cancers.

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    Yan Zhang

    Full Text Available Obesity, and in particular visceral obesity, has been associated with an increased risk of developing cancers as well as higher rates of mortality following diagnosis. The impact of obesity on adipose-derived stromal cells (ASC, which contribute to the formation of tumor stroma, is unknown. Here we hypothesized that visceral source and diet-induced obesity (DIO changes the ASC phenotype, contributing to the tumor promoting effects of obesity. We found that ASC isolated from subcutaneous (SC-ASC and visceral (V-ASC white adipose tissue(WAT of lean(Le and obese(Ob mice exhibited similar mesenchymal cell surface markers expression, and had comparable effects on ovarian cancer cell proliferation and migration. Obese and visceral derived ASC proliferated slower and exhibited impaired differentiation into adipocytes and osteocytes in vitro as compared to ASC derived from subcutaneous WAT of lean mice. Intraperitoneal co-injection of ovarian cancer cells with obese or visceral derived ASC, but not lean SC-ASC, increased growth of intraperitoneal ID8 tumors as compared to controls. Obese and V-ASC increased stromal infiltration of inflammatory cells, including CD3+ T cells and F4/80+ macrophages. Obese and visceral derived ASC, but not lean SC-ASC, increased expression of chemotactic factors IL-6, MIP-2, and MCP-1 when cultured with tumor cells. Overall, these results demonstrate that obese and V-ASC have a unique phenotype, with more limited proliferation and differentiation capacity but enhanced expression of chemotactic factors in response to malignant cells which support infiltration of inflammatory cells and support tumor growth and dissemination.

  19. Transport phenomena during freezing of adipose tissue derived adult stem cells.

    Science.gov (United States)

    Thirumala, Sreedhar; Gimble, Jeffrey M; Devireddy, Ram V

    2005-11-05

    In the present study a well-established differential scanning calorimeter (DSC) technique is used to measure the water transport phenomena during freezing of stromal vascular fraction (SVF) and adipose tissue derived adult stem (ADAS) cells at different passages (Passages 0 and 2). Volumetric shrinkage during freezing of adipose derived cells was obtained at a cooling rate of 20 degrees C/min in the presence of extracellular ice and two different, commonly used, cryoprotective agents, CPAs (10% DMSO and 10% Glycerol). The adipose derived cells were modeled as spheres of 50 microm diameter with an osmotically inactive volume (Vb) of 0.6Vo, where Vo is the isotonic cell volume. By fitting a model of water transport to the experimentally obtained volumetric shrinkage data, the "best-fit" membrane permeability parameters (reference membrane permeability to water, Lpg or Lpg[cpa] and the activation energy, ELp or ELp[cpa]) were determined. The "best-fit" membrane permeability parameters for adipose derived cells in the absence and presence of CPAs ranged from: Lpg=23.1-111.5x10(-15) m3/Ns (0.135-0.652 microm/min-atm) and ELp=43.1-168.8 kJ/mol (9.7-40.4 kcal/mol). Numerical simulations of water transport were then performed under a variety of cooling rates (5-100 degrees C/min) using the experimentally determined membrane permeability parameters. And finally, the simulation results were analyzed to predict the optimal rates of freezing adipose derived cells in the presence and absence of CPAs. Copyright (c) 2005 Wiley Periodicals, Inc.

  20. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose

    DEFF Research Database (Denmark)

    Bülow, J; Simonsen, L; Wiggins, D

    1999-01-01

    The integration of lipid metabolism in the splanchnic bed and in subcutaneous adipose tissue before and after ingestion of a 75 g glucose load was studied by Fick's principle in seven healthy subjects. Six additional subjects were studied during a hyperinsulinemic euglycemic clamp. Release of non...

  1. Basic fibroblast growth factor-treated adipose tissue-derived mesenchymal stem cell infusion to ameliorate liver cirrhosis via paracrine hepatocyte growth factor.

    Science.gov (United States)

    Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

    2015-06-01

    Recent studies show that adipose tissue-derived mesenchymal stem cells have potential clinical applications. However, the mechanism has not been fully elucidated yet. Here, we investigated the effect of basic fibroblast growth factor-treated adipose tissue-derived mesenchymal stem cells infusion on a liver fibrosis rat model and elucidated the underlying mechanism. Adipose tissue-derived mesenchymal stem cells were infused into carbon tetrachloride-induced hepatic fibrosis rats through caudal vein. Liver functions and pathological changes were assessed. A co-culture model was used to clarify the potential mechanism. Basic fibroblast growth factor treatment markedly improved the proliferation, differentiation, and hepatocyte growth factor expression ability of adipose tissue-derived mesenchymal stem cells. Although adipose tissue-derived mesenchymal stem cells infusion alone slightly ameliorated liver functions and suppressed fibrosis progression, basic fibroblast growth factor-treatment significantly enhanced the therapeutic effect in association with elevated hepatocyte growth factor expression. Moreover, double immunofluorescence staining confirmed that the infused cells located in fibrosis area. Furthermore, co-culture with adipose tissue-derived mesenchymal stem cell led to induction of hepatic stellate cell apoptosis and enhanced hepatocyte proliferation. However, these effects were significantly weakened by knockdown of hepatocyte growth factor. Mechanism investigation revealed that co-culture with adipose tissue-derived mesenchymal stem cells activated c-jun N-terminal kinase-p53 signaling in hepatic stellate cell and promoted apoptosis. Basic fibroblast growth factor treatment enhanced the therapeutic effect of adipose tissue-derived mesenchymal stem cells, and secretion of hepatocyte growth factor from adipose tissue-derived mesenchymal stem cells plays a critical role in amelioration of liver injury and regression of fibrosis. © 2015 Journal of

  2. Establishment and molecular characterization of mesenchymal stem cell lines derived from human visceral & subcutaneous adipose tissues.

    Science.gov (United States)

    Potdar, Pd; Sutar, Jp

    2010-01-01

    Mesenchymal stem cells (MSCs), are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, myocytes and adipocytes. We utilized adipose tissue as our primary source, since it is a rich source of MSCs as well as it can be harvested using a minimally invasive surgical procedure. Both visceral and subcutaneous adipose tissue (VSAT, SCAT respectively) samples were cultured using growth medium without using any substratum for their attachment. We observed growth of mesenchymal like cells within 15 days of culturing. In spite of the absence of any substratum, the cells adhered to the bottom of the petri dish, and spread out within 2 hours. Presently VSAT cells have reached at passage 10 whereas; SCAT cells have reached at passage 14. Morphologically MSCs obtained from visceral adipose tissue were larger in shape than subcutaneous adipose tissue. We checked these cells for presence or absence of specific stem cell molecular markers. We found that VSAT and SCAT cells confirmed their MSC phenotype by expression of specific MSC markers CD 105 and CD 13 and absence of CD34 and CD 45 markers which are specific for haematopoietic stem cells. These cells also expressed SOX2 gene confirming their ability of self-renewal as well as expressed OCT4, LIF and NANOG for their properties for pluripotency & plasticity. Overall, it was shown that adipose tissue is a good source of mesenchymal stem cells. It was also shown that MSCs, isolated from adipose tissue are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, cardiomyocytes, adipocytes and liver cells which may open a new era for cell based regenerative therapies for bone, cardiac and liver disorders.

  3. Establishment and Molecular Characterization of Mesenchymal Stem Cell Lines Derived From Human Visceral & Subcutaneous Adipose Tissues

    Directory of Open Access Journals (Sweden)

    Jyoti Prakash Sutar

    2010-01-01

    Full Text Available Mesenchymal stem cells (MSCs, are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, myocytes and adipocytes. We utilized adipose tissue as our primary source, since it is a rich source of MSCs as well as it can be harvested using a minimally invasive surgical procedure. Both visceral and subcutaneous adipose tissue (VSAT, SCAT respectively samples were cultured using growth medium without using any substratum for their attachment. We observed growth of mesenchymal like cells within 15 days of culturing. In spite of the absence of any substratum, the cells adhered to the bottom of the petri dish, and spread out within 2 hours. Presently VSAT cells have reached at passage 10 whereas; SCAT cells have reached at passage 14. Morphologically MSCs obtained from visceral adipose tissue were larger in shape than subcutaneous adipose tissue. We checked these cells for presence or absence of specific stem cell molecular markers. We found that VSAT and SCAT cells confirmed their MSC phenotype by expression of specific MSC markers CD 105 and CD13 and absence of CD34 and CD 45 markers which are specific for haematopoietic stem cells. These cells also expressed SOX2 gene confirming their ability of self-renewal as well as expressed OCT4, LIF and NANOG for their properties for pluripotency & plasticity. Overall, it was shown that adipose tissue is a good source of mesenchymal stem cells. It was also shown that MSCs, isolated from adipose tissue are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, cardiomyocytes, adipocytes and liver cells which may open a new era for cell based regenerative therapies for bone, cardiac and liver disorders.

  4. 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....

  5. Implantation of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in Foot Fat Pad in Rats.

    Science.gov (United States)

    Molligan, Jeremy; Mitchell, Reed; Bhasin, Priya; Lakhani, Aliya; Schon, Lew; Zhang, Zijun

    2015-11-01

    The foot fat pad (FFP) bears body weight and may become a source of foot pain during aging. This study investigated the regenerative effects of autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs) in the FFP of rats. Fat tissue was harvested from a total of 30 male Sprague-Dawley rats for isolation of AT-MSCs. The cells were cultured, adipogenic differentiation was induced for 1 week, and the AT-MSCs were labeled with fluorescent dye before injection. AT-MSCs (5 × 10(4) in 50 µL of saline) were injected into the second infradigital pad in the right hindfoot of the rat of origin. Saline only (50 µL) was injected into the corresponding fat pad in the left hind paw of each rat. Rats (n = 10) were euthanized at 1, 2, and 3 weeks, and the second infradigital fat pads were dissected for histologic examination. The fluorescence-labeled AT-MSCs were present in the foot pads throughout the 3-week experimental period. On histologic testing, the area of fat pad units (FPUs) in the fat pads that received AT-MSC injections was greater than that in the control fat pads. Although the thickness of septae was not changed by AT-MSC injections, the density of elastic fibers in the septae was increased in the fat pads with implanted AT-MSCs. In this short-term study, the implanted AT-MSCs largely survived and might have stimulated the expansion of individual FPUs and increased the density of elastic fibers in the FFP in this rat model. These data support the development of stem cell therapies for age-associated degeneration in FFP in humans. © The Author(s) 2015.

  6. Novel positively charged nanoparticle labeling for in vivo imaging of adipose tissue-derived stem cells.

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    Hiroshi Yukawa

    Full Text Available Stem cell transplantation has been expected to have various applications for regenerative medicine. However, in order to detect and trace the transplanted stem cells in the body, non-invasive and widely clinically available cell imaging technologies are required. In this paper, we focused on magnetic resonance (MR imaging technology, and investigated whether the trimethylamino dextran-coated magnetic iron oxide nanoparticle -03 (TMADM-03, which was newly developed by our group, could be used for labeling adipose tissue-derived stem cells (ASCs as a contrast agent. No cytotoxicity was observed in ASCs transduced with less than 100 µg-Fe/mL of TMADM-03 after a one hour transduction time. The transduction efficiency of TMADM-03 into ASCs was about four-fold more efficient than that of the alkali-treated dextran-coated magnetic iron oxide nanoparticle (ATDM, which is a major component of commercially available contrast agents such as ferucarbotran (Resovist, and the level of labeling was maintained for at least two weeks. In addition, the differentiation ability of ASCs labeled with TMADM-03 and their ability to produce cytokines such as hepatocyte growth factor (HGF, vascular endothelial growth factor (VEGF and prostaglandin E2 (PGE2, were confirmed to be maintained. The ASCs labeled with TMADM-03 were transplanted into the left kidney capsule of a mouse. The labeled ASCs could be imaged with good contrast using a 1T MR imaging system. These data suggest that TMADM-03 can therefore be utilized as a contrast agent for the MR imaging of stem cells.

  7. Effects of Hypoxia on the Immunomodulatory properties of Adipose tissue-derived Mesenchymal Stem Cells

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    M eRoemeling-Van Rhijn

    2013-07-01

    Full Text Available Adipose 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 than under standard culture conditions and ASC used for therapy therefore encounter a change from normoxic to hypoxic conditions. The effect of hypoxia on the regenerative potential of ASC has been investigated in a number of studies. The effect of hypoxia on the immunomodulatory function of ASC, however, remains to be determined. In the present study the effect of hypoxic (1% oxygen culture conditions on human ASC was examined. ASC showed no signs of toxicity under low oxygen levels and no major immunophenotypical changes were observed, apart from a down regulation of the marker CD105. Oxygen tension had no effect on the proliferation of ASC and colony forming unit (CFU efficiency remained the same under 1% and 20% oxygen. Under both oxygen levels ASC were capable of strong upregulation of the immunomodulatory molecules indolamine 2,3-dioxygenase (IDO and programmed death ligand-1 (PD-L1 upon stimulation with IFN- and TNF-, and, in addition, IDO activity as measured by the accumulation of L-kynurenine was not affected under hypoxia. The ability of ASC to inhibit anti-CD3/CD28 stimulated CD4+ and CD8+ T cell proliferation was enhanced under hypoxic conditions.The results of the present study demonstrate that the immunosuppressive capacity of ASC is maintained under hypoxic conditions. These findings are important for the therapeutic use of ASC and may be applied for the in vitro generation of ASC with improved functionality for therapeutic use.

  8. Effect of hypoxia on equine mesenchymal stem cells derived from bone marrow and adipose tissue

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    Ranera Beatriz

    2012-08-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs derived from bone marrow (BM-MSCs and adipose tissue (AT-MSCs are being applied to equine cell therapy. The physiological environment in which MSCs reside is hypoxic and does not resemble the oxygen level typically used in in vitro culture (20% O2. This work compares the growth kinetics, viability, cell cycle, phenotype and expression of pluripotency markers in both equine BM-MSCs and AT-MSCs at 5% and 20% O2. Results At the conclusion of culture, fewer BM-MSCs were obtained in hypoxia than in normoxia as a result of significantly reduced cell division. Hypoxic AT-MSCs proliferated less than normoxic AT-MSCs because of a significantly higher presence of non-viable cells during culture. Flow cytometry analysis revealed that the immunophenotype of both MSCs was maintained in both oxygen conditions. Gene expression analysis using RT-qPCR showed that statistically significant differences were only found for CD49d in BM-MSCs and CD44 in AT-MSCs. Similar gene expression patterns were observed at both 5% and 20% O2 for the remaining surface markers. Equine MSCs expressed the embryonic markers NANOG, OCT4 and SOX2 in both oxygen conditions. Additionally, hypoxic cells tended to display higher expression, which might indicate that hypoxia retains equine MSCs in an undifferentiated state. Conclusions Hypoxia attenuates the proliferative capacity of equine MSCs, but does not affect the phenotype and seems to keep them more undifferentiated than normoxic MSCs.

  9. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

    2017-03-01

    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. [Pretreatment with cyclosporin A nanoparticles emulsion protects apoptosis of swine adipose tissue-derived stem cells].

    Science.gov (United States)

    Yin, Qiao-xiang; Pei, Zhi-yong; Wang, Heng; Zhao, Yu-sheng

    2013-06-01

    To investigate the effect of cyclosporine A-nanoparticles emulsion (CsA-NP) on protecting apoptosis of swine adipose tissue-derived stem cells (ASC ) and related mechanisms. ASC were randomized to six groups: control group,single H2O2 group,CsA or CsA-NP 0.1 mg/ml+H2O2 group,CsA or CsA-NP 1.0 mg/ml+H2O2 group, CsA or CsA-NP 5.0 mg/ml+H2O2 group,CsA or CsA-NP 10.0 mg/ml+H2O2 group. ASC apoptosis was induced by hydrogen peroxide (H2O2100 µmol/L) in vitro. The morphology of apoptotic cells was observed and the number of apoptotic cells was measured. Apoptosis of ASC was detected by flow cytometry using an apoptosis kit. Cell activity was determined by CCK-8 assay. Caspase-3 activity was detected by applying a caspase-3 assay kit. Expression of cytochrome C was investigated by Western blot. H2O2 induced ASC apoptosis was evidenced by morphological and biochemical changes,which could be significantly reduced by pre-treatment with CsA or CsA-NP at concentration of 0.1-10.0 mg/ml, and the best effect was observed at concentration of 5 mg/ml (apoptosis rate: CsA: 10.6% ± 2.8% vs. 25.2% ± 3.8%; CsA-NP: 6.2% ± 2.6% vs. 25.2% ± 3.6% in control group, all P NP pre-treated ASC at concentration of 0.1-10.0 mg/ml than in H2O2 group (P NP (0.1-10.0 mg/ml) significantly down -regulated caspase-3 activity. Furthermore, CsA or CsA-NP (5 mg/ml) completely inhibited the H2O2-induced release of cytochrome C. These results suggest that CsA-NP and CsA could protect the oxidative stress-induced ASC apoptosis through decreasing the activation of caspase-3 and inhibiting the release of cytochrome C.

  13. Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?

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    Inatani, Hiroyuki; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Takeuchi, Akihiko; Miwa, Shinji; Higuchi, Takashi; Abe, Kensaku; Taniguchi, Yuta; Yamada, Satoshi; Asai, Kiyofumi; Otsuka, Takanobu; Tsuchiya, Hiroyuki

    2017-06-01

    The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs. We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients. During tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations. In terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency

  14. Ultra-structural morphology of long-term cultivated white adipose tissue-derived stem cells.

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    Varga, Ivan; Miko, Michal; Oravcová, Lenka; Bačkayová, Tatiana; Koller, Ján; Danišovič, Ľuboš

    2015-12-01

    White adipose tissue was long perceived as a passive lipid storage depot but it is now considered as an active and important endocrine organ. It also harbours not only adipocytes and vascular cells but also a wide array of immunologically active cells, including macrophages and lymphocytes, which may induce obesity-related inflammation. Recently, adipose tissue has been reported as a source of adult mesenchymal stem cells with wide use in regenerative medicine and tissue engineering. Their relatively non-complicated procurement and collection (often performed as liposuction during aesthetic surgery) and grand plasticity support this idea even more. We focused our research on exploring the issues of isolation and long-term cultivation of mesenchymal stem cells obtained from adipose tissue. Ultra-structural morphology of the cells cultivated in vitro has been studied and analysed in several cultivation time periods and following serial passages--up to 30 passages. In the first passages they had ultra-structural characteristics of cells with high proteosynthetic activity. Within the cytoplasm, big number of small lipid droplets and between them, sparsely placed, small and inconspicuous, electron-dense, lamellar bodies, which resembled myelin figures were observed. The cells from the later passages contained high number of lamellar electron-dense structures, which filled out almost the entire cytoplasm. In between, mitochondria were often found. These bodies were sometimes small and resembled myelin figures, but several of them reached huge dimensions (more than 1 µm) and their lamellar structure was not distinguishable. We did not have an answer to the question about their function, but they probably represented the evidence of active metabolism of lipids present in the cytoplasm of these cells or represented residual bodies, which arise after the breakdown of cellular organelles, notably mitochondria during long-term cultivation.

  15. Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue

    DEFF Research Database (Denmark)

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

    2016-01-01

    , low-grade inflammation, expression of fat translocase and scavenger receptor CD36, and the scavenger receptor class B type 1 (SR-BI). SR-BI binds to both lipids and lipopolysaccharide (LPS) from Gram-negative bacteria, which may promote incorporation of LPS in chylomicrons (CMs). These CMs...... activity absorb LPS-rich lipoproteins. In addition, macrophages in adipose tissue internalize LPS-lipoproteins. This may contribute to the polarization from M2 to M1 phenotype, which is a consequence of increased LPS delivery into the tissue during hypertrophy. In conclusion, evidence suggests that LPS...

  16. 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.

  17. Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.

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    Keith A Russell

    Full Text Available Mesenchymal stromal cells (MSC hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies.We hypothesized that canine adipose tissue (AT and bone marrow (BM MSC (derived from the same dogs will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1 proliferation rate, 2 cell surface marker expression, 3 DNA methylation levels, 4 potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5 immunomodulatory potency in vitro.1 AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days for passage (P 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21. 2 Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3 Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4 Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-β3-based induction medium. 5 Immunomodulatory capacity was equal regardless of cell source when tested in

  18. Effects of platelet-rich plasma, adipose-derived stem cells, and stromal vascular fraction on the survival of human transplanted adipose tissue.

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    Kim, Deok-Yeol; Ji, Yi-Hwa; Kim, Deok-Woo; Dhong, Eun-Sang; Yoon, Eul-Sik

    2014-11-01

    Traditional adipose tissue transplantation has unpredictable viability and poor absorption rates. Recent studies have reported that treatment with platelet-rich plasma (PRP), adipose-derived stem cells (ASCs), and stromal vascular fraction (SVF) are related to increased survival of grafted adipose tissue. This study was the first simultaneous comparison of graft survival in combination with PRP, ASCs, and SVF. Adipose tissues were mixed with each other, injected subcutaneously into the back of nude mice, and evaluated at 4, 8, and 12 weeks. Human adipocytes were grossly maintained in the ASCs and SVF mixtures. Survival of the adipose tissues with PRP was observed at 4 weeks and with SVF at 8 and 12 weeks. At 12 weeks, volume reduction in the ASCs and SVF mixtures were 36.9% and 32.1%, respectively, which were significantly different from that of the control group without adjuvant treatment, 51.0%. Neovascular structures were rarely observed in any of the groups. Our results suggest that the technique of adding ASCs or SVF to transplanted adipose tissue might be more effective than the conventional grafting method. An autologous adipose tissue graft in combination with ASCs or SVF may potentially contribute to stabilization of engraftment.

  19. 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

  20. Human adipose tissue-derived tenomodulin positive subpopulation of stem cells: A promising source of tendon progenitor cells.

    Science.gov (United States)

    Gonçalves, A I; Gershovich, P M; Rodrigues, M T; Reis, R L; Gomes, M E

    2018-03-01

    Cell-based therapies are of particular interest for tendon and ligament regeneration given the low regenerative potential of these tissues. Adipose tissue is an abundant source of stem cells, which may be employed for the healing of tendon lesions. However, human adult multipotent adipose-derived stem cells (hASCs) isolated from the stromal vascular fraction of adipose tissue originate highly heterogeneous cell populations that hinder their use in specific tissue-oriented applications. In this study, distinct subpopulations of hASCs were immunomagnetic separated and their tenogenic differentiation capacity evaluated in the presence of several growth factors (GFs), namely endothelial GF, basic-fibroblast GF, transforming GF-β1 and platelet-derived GF-BB, which are well-known regulators of tendon development, growth and healing. Among the screened hASCs subpopulations, tenomodulin-positive cells were shown to be more promising for tenogenic applications and therefore this subpopulation was further studied, assessing tendon-related markers (scleraxis, tenomodulin, tenascin C and decorin) both at gene and protein level. Additionally, the ability for depositing collagen type I and III forming extracellular matrix structures were weekly assessed up to 28 days. The results obtained indicated that tenomodulin-positive cells exhibit phenotypical features of tendon progenitor cells and can be biochemically induced towards tenogenic lineage, demonstrating that this subset of hASCs can provide a reliable source of progenitor cells for therapies targeting tendon regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Autologous adipose tissue-derived stem cells induce persistent bone-like tissue in osteonecrotic femoral heads.

    Science.gov (United States)

    Pak, Jaewoo

    2012-01-01

    Osteonecrosis, also known as avascular necrosis, of the femoral head is a debilitating disorder that commonly affects 30- to 50-year-old individuals. Currently, definitive treatment is limited to total hip replacement. However, recent studies have demonstrated bone regeneration in the femoral head after the infusion of bone marrow-derived mesenchymal stem cells. In addition, local injection of adipose tissue-derived stem cells has been shown to regenerate medullary bone-like tissue 3 months after treatment. However, there have been no long-term follow-up studies on humans treated with adipose tissue-derived stem cells for osteonecrosis. To determine if treatment with adipose tissue-derived stem cells and platelet-rich plasma leads to the regeneration of medullary bone-like tissue and long-term reduction of hip pain in patients with femoral head osteonecrosis. This report of two clinical cases was in compliance with the Declaration of Helsinki. Also, the Korean Food and Drug Administration has allowed the use of adipose tissue-derived stem cells (ADSCs) in medical treatments since 2009. To obtain ADSCs, lipoaspirates were obtained from lower abdominal subcutaneous adipose tissue. The stromal vascular fraction was separated from the lipoaspirates by centrifugation after treatment with collagenase. The stem-cell-containing stromal vascular fraction was mixed with calcium chloride-activated platelet rich plasma and hyaluronic acid, and this mixture was then injected into the diseased hip. The affected hip was reinjected with calcium chloride-activated platelet rich plasma weekly for 4 weeks. Patients were subjected to pre- and post-treatment magnetic resonance imaging (MRI) scans. Two patients (34- and 39-year-old men) with femoral head osteonecrosis and severe hip pain were treated with adipose-derived stem cells. The MRI scans of the affected hip in both patients showed segmental areas of low signal intensity (T1 axial views) in the subchondral bones with a "double

  2. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue.

    Science.gov (United States)

    Heo, June Seok; Choi, Youjeong; Kim, Han-Soo; Kim, Hyun Ok

    2016-01-01

    Mesenchymal stem cells (MSCs) are clinically useful due to their capacity for self-renewal, their immunomodulatory properties and tissue regenerative potential. These cells can be isolated from various tissues and exhibit different potential for clinical applications according to their origin, and thus comparative studies on MSCs from different tissues are essential. In this study, we investigated the immunophenotype, proliferative potential, multilineage differentiation and immunomodulatory capacity of MSCs derived from different tissue sources, namely bone marrow, adipose tissue, the placenta and umbilical cord blood. The gene expression profiles of stemness-related genes [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box (SOX)2, MYC, Krüppel-like factor 4 (KLF4), NANOG, LIN28 and REX1] and lineage‑related and differentiation stage-related genes [B4GALNT1 (GM2/GS2 synthase), inhibin, beta A (INHBA), distal-less homeobox 5 (DLX5), runt-related transcription factor 2 (RUNX2), proliferator‑activated receptor gamma (PPARG), CCAAT/enhancer-binding protein alpha (C/EBPA), bone morphogenetic protein 7 (BMP7) and SOX9] were compared using RT-PCR. No significant differences in growth rate, colony-forming efficiency and immunophenotype were observed. Our results demonstrated that MSCs derived from bone marrow and adipose tissue shared not only in vitro tri-lineage differentiation potential, but also gene expression profiles. While there was considerable inter-donor variation in DLX5 expression between MSCs derived from different tissues, its expression appears to be associated with the osteogenic potential of MSCs. Bone marrow-derived MSCs (BM-MSCs) significantly inhibited allogeneic T cell proliferation possibly via the high levels of the immunosuppressive cytokines, IL10 and TGFB1. Although MSCs derived from different tissues and fibroblasts share many characteristics, some of the marker genes, such as B4GALNT1 and DLX5 may be useful for

  3. The major plant-derived cannabinoid Δ(9)-tetrahydrocannabinol promotes hypertrophy and macrophage infiltration in adipose tissue.

    Science.gov (United States)

    Wong, A; Gunasekaran, N; Hancock, D P; Denyer, G S; Meng, L; Radford, J L; McGregor, I S; Arnold, J C

    2012-02-01

    Synthetic cannabinoid receptor agonists activate lipoprotein lipase and the formation of lipid droplets in cultured adipocytes. Here we extend this work by examining whether Δ(9)-tetrahydrocannabinol (THC), a major plant-derived cannabinoid, increases adipocyte size in vivo. Further, possibly as a consequence of hypertrophy, we hypothesize that THC exposure promotes macrophage infiltration into adipose tissue, an inflammatory state observed in obese individuals. Rats repeatedly exposed to THC in vivo had reduced body weight, fat pad weight, and ingested less food over the drug injection period. However, THC promoted adipocyte hypertrophy that was accompanied by a significant increase in cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) expression, an enzyme important in packaging triglycerides. We also showed that THC induced macrophage infiltration and increased expression of the inflammatory cytokine tumor necrosis factor alpha (TNF-α) in adipose tissue but did not induce apoptosis as measured by TUNEL staining. That THC increased adipocyte cell size in the absence of greater food intake, body weight and fat provides a unique model to explore mechanisms underlying changes in adipocyte size associated with a mild inflammatory state in fat tissue. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells

    Science.gov (United States)

    Garcia, MM; Fandel, TM; Lin, G; Shindel, AW; Banie, L; Lin, CS; Lue, TF

    2010-01-01

    Introduction Impotence, or erectile dysfunction (ED), is a major complication of type-II diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim To determine whether autologous adipose tissue derived stem cells (ADSC) injected into the penis of impotent obese type-II diabetic rats survive and improve erectile function. Main outcome measures Intracorporal pressure (ICP) increase with cavernous nerve (CN) electrostimulation, immunohistochemistry, real-time PCR, and serum glucose and testosterone assays. Methods Twenty-two 10-week old male fatty type-II diabetic ZDF rats underwent weight and blood glucose measurement every 2 weeks. At age 22 weeks, all animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence, and paragonadal adipose tissue (5 grams) was harvested and digested to yield 1.5 million ADSC. Impotent animals were randomized to ADSC treatment and sham control groups. At age 23 weeks, treatment group animals underwent penile injection of 1.5 million ADSC; control group animals received only PBS. Erectile function studies were repeated at age 26 weeks, followed by harvest of tissue and serum. Results Pre- and post-treatment stimulation ICP increase was significantly different between groups (ppenis appear to survive and improve erectile function. Autologous ADSC therapy is a promising approach to treat diabetic impotence. PMID:20104670

  5. 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.

  6. Safety of Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cell Intraspinal Transplantation in Dogs with Chronic Spinal Cord Injury

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    Cláudia Cardoso Maciel Escalhão

    2017-01-01

    Full Text Available This is a pilot clinical study primarily designed to assess the feasibility and safety of X-ray-guided percutaneous intraspinal injection of allogeneic canine adipose tissue-derived mesenchymal stem cells in dogs with chronic spinal cord injury. Six dogs with chronic paraplegia (≥six months were intraparenchymally injected with allogeneic cells in the site of lesion. Cells were obtained from subcutaneous adipose tissue of a healthy dog, cultured to passage 3, labeled with 99mTechnetium, and transplanted into the lesion by percutaneous X-ray-guided injection. Digital X-ray efficiently guided cell injection as 99mTechnetium-labeled cells remained in the injection site for at least 24 hours after transplantation. No adverse effects or complications (infection, neuropathic pain, or worsening of neurological function were observed during the 16-week follow-up period after transplantation. Three animals improved locomotion as assessed by the Olby scale. One animal walked without support, but no changes in deep pain perception were observed. We conclude that X-ray-guided percutaneous intraspinal transplantation of allogeneic cells in dogs with chronic spinal cord injury is feasible and safe. The efficacy of the treatment will be assessed in a new study involving a larger number of animals.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  9. [Isolation, culture and identification of adipose-derived stem cells from SD rat adipose tissues subjected to long-term cryopreservation].

    Science.gov (United States)

    Liu, Qin; Wang, Liping; Chen, Fang; Zhang, Yi

    2017-02-01

    Objective To study the feasibility of isolation and culture of adipose-derived stem cells (ADSCs) from SD rat adipose tissues subjected to long-term cryopreservation. Methods We took inguinal fat pads from healthy SD rats. Adipose tissues were stored with 100 mL/L dimethyl sulfoxide (DMSO) combined with 900 mL/L fetal bovine serum (FBS) in liquid nitrogen. Three months later, the adipose tissues were resuscitated for the isolation and culture of ADSCs. The growth status and morphology were observed. The growth curve and cell surface markers CD29, CD45, CD90 of the 3rd passage cells were analyzed respectively by CCK-8 assay and immunocytochemistry. The 3rd passage cells were induced towards adipogenic lineages and osteogenic lineages by different inducers, and the resulting cells were examined separately by oil red O staining and alizarin red staining. Results The ADSCs obtained from SD rat adipose tissues subjected to long-term cryopreservation showed a spindle-shape appearance and had a good proliferation ability. The cell growth curve was typical "S" curve. Immunocytochemistry showed that the 3rd passage cells were positive for CD29 and CD90, while negative for CD45. The cells were positive for oil red O staining after adipogenic induction, and also positive for alizarin red staining after osteogenic induction. Conclusion The ADSCs can be isolated from SD rat adipose tissues subjected to long-term cryopreservation.

  10. Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

    Science.gov (United States)

    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

  11. Human adipose tissue derived pericytes increase life span in Utrn (tm1Ked) Dmd (mdx) /J mice.

    Science.gov (United States)

    Valadares, M C; Gomes, J P; Castello, G; Assoni, A; Pellati, M; Bueno, C; Corselli, M; Silva, H; Bartolini, P; Vainzof, M; Margarido, P F; Baracat, E; Péault, B; Zatz, M

    2014-12-01

    Duchenne muscular dystrophy (DMD) is still an untreatable lethal X-linked disorder, which affects 1 in 3500 male births. It is caused by the absence of muscle dystrophin due to mutations in the dystrophin gene. The potential regenerative capacity as well as immune privileged properties of mesenchymal Stem Cells (MSC) has been under investigation for many years in an attempt to treat DMD. One of the questions to be addressed is whether stem cells from distinct sources have comparable clinical effects when injected in murine or canine muscular dystrophy animal models. Many studies comparing different stem cells from various sources were reported but these cells were obtained from different donors and thus with different genetic backgrounds. Here we investigated whether human pericytes obtained from 4 different tissues (muscle, adipose tissue, fallopian tube and endometrium) from the same donor have a similar clinical impact when injected in double mutant Utrn (tm1Ked) Dmd (mdx) /J mice, a clinically relevant model for DMD. After a weekly regimen of intraperitoneal injections of 10(6) cells per 8 weeks we evaluated the motor ability as well as the life span of the treated mice as compared to controls. Our experiment showed that only adipose tissue derived pericytes are able to increase significantly (39 days on average) the life span of affected mice. Microarray analysis showed an inhibition of the interferon pathway by adipose derived pericytes. Our results suggest that the clinical benefit associated with intraperitoneal injections of these adult stem cells is related to immune modulation rather than tissue regeneration.

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

    Science.gov (United States)

    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.

  13. 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.

  14. 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.

  15. Engineered cartilage regeneration from adipose tissue derived-mesenchymal stem cells: A morphomolecular study on osteoblast, chondrocyte and apoptosis evaluation.

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    Szychlinska, Marta Anna; Castrogiovanni, Paola; Nsir, Houda; Di Rosa, Michelino; Guglielmino, Claudia; Parenti, Rosalba; Calabrese, Giovanna; Pricoco, Elisabetta; Salvatorelli, Lucia; Magro, Gaetano; Imbesi, Rosa; Mobasheri, Ali; Musumeci, Giuseppe

    2017-08-15

    The poor self-repair capacity of cartilage tissue in degenerative conditions, such as osteoarthritis (OA), has prompted the development of a variety of therapeutic approaches, such as cellular therapies and tissue engineering based on the use of mesenchymal stem cells (MSCs). The aim of this study is to demonstrate, for the first time, that the chondrocytes differentiated from rat adipose tissue derived-MSCs (AMSCs), are able to constitute a morphologically and biochemically healthy hyaline cartilage after 6 weeks of culture on a Collagen Cell Carrier (CCC) scaffold. In this study we evaluated the expression of some osteoblasts (Runt-related transcription factor 2 (RUNX2) and osteocalcin), chondrocytes (collagen I, II and lubricin) and apoptosis (caspase-3) biomarkers in undifferentiated AMSCs, differentiated AMSCs in chondrocytes cultured in monolayer and AMSCs-derived chondrocytes seeded on CCC scaffolds, by different techniques such as immunohistochemistry, ELISA, Western blot and gene expression analyses. Our results showed the increased expression of collagen II and lubricin in AMSCs-derived chondrocytes cultured on CCC scaffolds, whereas the expression of collagen I, RUNX2, osteocalcin and caspase-3 resulted decreased, when compared to the controls. In conclusion, this innovative basic study could be a possible key for future therapeutic strategies for articular cartilage restoration through the use of CCC scaffolds, to reduce the morbidity from acute cartilage injuries and degenerative joint diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Subcutaneous Construction of Engineered Adipose Tissue with Fat Lobule-Like Structure Using Injectable Poly-Benzyl-L-Glutamate Microspheres Loaded with Adipose-Derived Stem Cells.

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    Wentao Sun

    Full Text Available Porous microcarriers were fabricated from synthesized poly(γ-benzyl-L-glutamate (PBLG polymer to engineer adipose tissue with lobule-like structure via the injectable approach. The adipogenic differentiation of human adipose-derived stem cells (hASCs seeded on porous PBLG microcarriers was determined by adipogenic gene expression and glycerol-3-phosphate dehydrogenase enzyme activity. In vitro adipogenic cultivation was performed for 7 days, and induced hASC/PBLG complex (Adi-ASC/PBLG group was subcutaneously injected into nude mice. Injections of PBLG microcarriers alone (PBLG group and non-induced hASC/PBLG complex (ASC/PBLG group served as controls. Newly formed tissues were harvested after 4 and 8 weeks. Generation of subcutaneous adipose tissue with typical lobule-like structure separated by fibrous septa was observed upon injection of adipogenic-induced hASC/microsphere complex. Adipogenesis significantly increased in the Adi-ASC/PBLG group compared with the control groups. The angiogenesis in the engineered adipose tissue was comparable to that in normal tissue as determined by capillary density and luminal diameter. Cell tracking assay demonstrated that labeled hASCs remained detectable in the neo-generated tissues 8 weeks post-injection using green fluorescence protein-labeled hASCs. These results indicate that adipose tissue with typical lobule-like structure could be engineered using injectable porous PBLG microspheres loaded with adipogenic-induced hASCs.

  17. Subcutaneous Construction of Engineered Adipose Tissue with Fat Lobule-Like Structure Using Injectable Poly-Benzyl-L-Glutamate Microspheres Loaded with Adipose-Derived Stem Cells.

    Science.gov (United States)

    Sun, Wentao; Fang, Jianjun; Yong, Qi; Li, Sufang; Xie, Qingping; Yin, Jingbo; Cui, Lei

    2015-01-01

    Porous microcarriers were fabricated from synthesized poly(γ-benzyl-L-glutamate) (PBLG) polymer to engineer adipose tissue with lobule-like structure via the injectable approach. The adipogenic differentiation of human adipose-derived stem cells (hASCs) seeded on porous PBLG microcarriers was determined by adipogenic gene expression and glycerol-3-phosphate dehydrogenase enzyme activity. In vitro adipogenic cultivation was performed for 7 days, and induced hASC/PBLG complex (Adi-ASC/PBLG group) was subcutaneously injected into nude mice. Injections of PBLG microcarriers alone (PBLG group) and non-induced hASC/PBLG complex (ASC/PBLG group) served as controls. Newly formed tissues were harvested after 4 and 8 weeks. Generation of subcutaneous adipose tissue with typical lobule-like structure separated by fibrous septa was observed upon injection of adipogenic-induced hASC/microsphere complex. Adipogenesis significantly increased in the Adi-ASC/PBLG group compared with the control groups. The angiogenesis in the engineered adipose tissue was comparable to that in normal tissue as determined by capillary density and luminal diameter. Cell tracking assay demonstrated that labeled hASCs remained detectable in the neo-generated tissues 8 weeks post-injection using green fluorescence protein-labeled hASCs. These results indicate that adipose tissue with typical lobule-like structure could be engineered using injectable porous PBLG microspheres loaded with adipogenic-induced hASCs.

  18. Elevated Expression of Dkk-1 by Glucocorticoid Treatment Impairs Bone Regenerative Capacity of Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Kato, Toshiki; Khanh, Vuong Cat; Sato, Kazutoshi; Kimura, Kenichi; Yamashita, Toshiharu; Sugaya, Hisashi; Yoshioka, Tomokazu; Mishima, Hajime; Ohneda, Osamu

    2018-01-15

    Glucocorticoids are steroid hormones used as anti-inflammatory treatments. However, this strong immunomodulation causes undesirable side effects that impair bones, such as osteoporosis. Glucocorticoid therapy is a major risk factor for developing steroid-induced osteonecrosis of the femur head (ONFH). Since ONFH is incurable, therapy with mesenchymal stem cells (MSCs) that can differentiate into osteoblasts are a first-line choice. Bone marrow-derived MSCs (BM-MSCs) are often used as a source of stem cell therapy for ONFH, but their proliferative activity is impaired after steroid treatment. Adipose tissue-derived MSCs (AT-MSCs) may be an attractive alternative source; however, it is unknown whether AT-MSCs from steroid-induced ONFH (sAT-MSCs) have the same differentiation ability as BM-MSCs or normal AT-MSCs (nAT-MSCs). In this study, we demonstrate that nAT-MSCs chronically exposed to glucocorticoids show lower alkaline phosphatase activity leading to reduced osteogenic differentiation ability. This impaired osteogenesis is mediated by high expression of Dickkopf1 (Dkk-1) that inhibits wnt/β-catenin signaling. Increased Dkk-1 also causes impaired osteogenesis along with reductions in bone regenerative capacity in sAT-MSCs. Of note, plasma Dkk-1 levels are elevated in steroid-induced ONFH patients. Collectively, our findings suggest that glucocorticoid-induced expression of Dkk-1 could be a key factor in modulating the differentiation ability of MSCs used for ONFH and other stem cell therapies.

  19. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

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    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.

  20. From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Gabr

    2017-01-01

    Full Text Available The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs and adipose tissue-derived mesenchymal stem cells (AT-MSCs, for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs, was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.

  1. 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

  2. Influence of low energy laser irradiation on the clinical treatment potential of adipose tissue-derived stem cells

    Directory of Open Access Journals (Sweden)

    Xuan LIAO

    2016-10-01

    Full Text Available Objective  To investigate the effects of low level gallium aluminum arsenide (GaAlAs laser irradiation on proliferation, cytokine secretion and adipogenic differentiation of cultured human adipose tissue-derived stem cells (hADSCs, and to find a safe and effective method for improving clinical treatment effect of ADSC. Methods  The cultured hADSCs from human adipose tissue were treated by using 650nm GaAlAs laser irradiation at a single of 2, 4 and 8J/cm2 respectively. Cell proliferation was quantified by MTT assay, cytokine secretion was determined by ELISA, and adipogenic differentiation was examined by oil red staining respectively. In addition, the expression profiles of putative hADSC surface markers were determined by real-time PCR. Results  MTT assay showed that treatment with GaAlAs laser irradiation at 4J/cm2 and 8J/cm2 (especially 4J/cm2 markedly promoted ADSCs proliferation from day 4 to day 6 after irradiation, when compared with the unirradiated group (P<0.05. ELISA results showed that the concentrations of VEGF, PDGF and TGF-βin culture supernatant were 287.5±15.2pg/ml, 36.0±0.7ng/ ml, and 292.6±10.5pg/ml when hADSCs were exposed to 4J/cm2 GaAlAs laser, and they were significantly higher than those of unirradiated group (145.3±21.6pg/ml, 26.7±0.6ng/ml and 130.6±6.0pg/ml, respectively, P<0.05. Quantitative PCR showed that the mRNA expression levels of cell surface marker CD13, CD29, CD44 and CD90 in hADSCs exposed to 4J/cm2 GaAlAs laser were 1.19, 22.05, 4.38 and 7.22 fold of those in unirradiated group (P<0.05. And the oil red staining revealed that GaAlAs laser irradiation could markedly accelerate the adipogenic differentiation of hADSCs (P<0.05. Conclusions  Low energy laser irradiation is a simple, safe and effective method, which can enhance the proliferation, cytokine secretion and adipogenic differentiation of ADSCs, may help to improve the therapeutic effect of ADSCs by clinical transformation application

  3. Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells.

    Science.gov (United States)

    Ritter, Andreas; Friemel, Alexandra; Fornoff, Friderike; Adjan, Mouhib; Solbach, Christine; Yuan, Juping; Louwen, Frank

    2015-10-27

    Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with tumor initiation and metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to cancer cells, whereas visceral adipose-derived stem cells incline to be "epithelial"-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of breast cancer cells by cell-cell contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs affect the low malignant breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell lymphoma and breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of breast cancer cells and render them resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727.

  4. Canine adipose tissue-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating T cells in rats.

    Science.gov (United States)

    Kim, Hyun-Wook; Song, Woo-Jin; Li, Qiang; Han, Sei-Myoung; Jeon, Kee-Ok; Park, Sang-Chul; Ryu, Min-Ok; Chae, Hyung-Kyu; Kyeong, Kweon; Youn, Hwa-Young

    2016-12-30

    Severe acute pancreatitis (SAP) is associated with systemic complications and high mortality rate in dogs. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in several inflammation models. In the present study, the effects of canine adipose tissue-derived (cAT)-MSCs in a rat model of SAP induced by retrograde injection of 3% sodium taurocholate solution into the pancreatic duct were investigated. cAT-MSCs labeled with dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchlorate (1 × 10⁷ cells/kg) were systemically administered to rats and pancreatic tissue was collected three days later for histopathological, quantitative real-time polymerase chain reaction, and immunocytochemical analyses. Greater numbers of infused cAT-MSCs were detected in the pancreas of SAP relative to sham-operated rats. cAT-MSC infusion reduced pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis, and decreased pancreatic expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, -6, -12, -17, and -23 and interferon-γ, while stimulating expression of the anti-inflammatory cytokines IL-4 and IL-10 in SAP rats. Moreover, cAT-MSCs decreased the number of clusters of differentiation 3-positive T cells and increased that of forkhead box P3-positive T cells in the injured pancreas. These results indicate that cAT-MSCs can be effective as a cell-based therapeutic strategy for treatment of SAP in dogs.

  5. Vanillin attenuates negative effects of ultraviolet A on the stemness of human adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Lee, Sang Yeol; Park, See-Hyoung; Kim, Mi Ok; Lim, Inhwan; Kang, Mingyeong; Oh, Sae Woong; Jung, Kwangseon; Jo, Dong Gyu; Cho, Il-Hoon; Lee, Jongsung

    2016-10-01

    Ultraviolet A (UVA) irradiation induces various changes in cell biology. The objective of this study was to determine the effect of vanillin on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). UVA-antagonizing mechanisms of vanillin were also examined. The results revealed that vanillin attenuated UVA-induced reduction of the proliferative potential and stemness of hAMSCs evidenced by increased proliferative activity in BrdU incorporation assay and upregulation of stemness-related genes (OCT4, NANOG and SOX2) in response to vanillin treatment. UVA-induced reduction in mRNA level of hypoxia-inducible factor (HIF)-1α was significantly recovered by vanillin. In addition, the antagonizing effect of vanillin on UVA was found to be mediated by reduced production of PGE2 through inhibiting JNK and p38 MAPK. Taken together, these findings showed that vanillin could improve the reduced stemness of hAMSCs induced by UVA. The effect of vanillin is mediated by upregulating HIF-1α via inhibiting PGE2-cAMP signaling. Therefore, vanillin might be used as an antagonizing agent to mitigate the effects of UVA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Gene expression analysis of human adipose tissue-derived stem cells during the initial steps of in vitro osteogenesis.

    Science.gov (United States)

    Robert, Anny Waloski; Angulski, Addeli Bez Batti; Spangenberg, Lucia; Shigunov, Patrícia; Pereira, Isabela Tiemy; Bettes, Paulo Sergio Loiacono; Naya, Hugo; Correa, Alejandro; Dallagiovanna, Bruno; Stimamiglio, Marco Augusto

    2018-03-16

    Mesenchymal stem cells (MSCs) have been widely studied with regard to their potential use in cell therapy protocols and regenerative medicine. However, a better comprehension about the factors and molecular mechanisms driving cell differentiation is now mandatory to improve our chance to manipulate MSC behavior and to benefit future applications. In this work, we aimed to study gene regulatory networks at an early step of osteogenic differentiation. Therefore, we analyzed both the total mRNA and the mRNA fraction associated with polysomes on human adipose tissue-derived stem cells (hASCs) at 24 h of osteogenesis induction. The RNA-seq results evidenced that hASC fate is not compromised with osteogenesis at this time and that 21 days of continuous cell culture stimuli are necessary for full osteogenic differentiation of hASCs. Furthermore, early stages of osteogenesis induction involved gene regulation that was linked to the management of cell behavior in culture, such as the control of cell adhesion and proliferation. In conclusion, although discrete initial gene regulation related to osteogenesis occur, the first 24 h of induction is not sufficient to trigger and drive in vitro osteogenic differentiation of hASCs.

  7. In Vivo Tracking of Murine Adipose Tissue-Derived Multipotent Adult Stem Cells and Ex Vivo Cross-Validation

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    Chiara Garrovo

    2013-01-01

    Full Text Available Stem cells are characterized by the ability to renew themselves and to differentiate into specialized cell types, while stem cell therapy is believed to treat a number of different human diseases through either cell regeneration or paracrine effects. Herein, an in vivo and ex vivo near infrared time domain (NIR TD optical imaging study was undertaken to evaluate the migratory ability of murine adipose tissue-derived multipotent adult stem cells [mAT-MASC] after intramuscular injection in mice. In vivo NIR TD optical imaging data analysis showed a migration of DiD-labelled mAT-MASC in the leg opposite the injection site, which was confirmed by a fibered confocal microendoscopy system. Ex vivo NIR TD optical imaging results showed a systemic distribution of labelled cells. Considering a potential microenvironmental contamination, a cross-validation study by multimodality approaches was followed: mAT-MASC were isolated from male mice expressing constitutively eGFP, which was detectable using techniques of immunofluorescence and qPCR. Y-chromosome positive cells, injected into wild-type female recipients, were detected by FISH. Cross-validation confirmed the data obtained by in vivo/ex vivo TD optical imaging analysis. In summary, our data demonstrates the usefulness of NIR TD optical imaging in tracking delivered cells, giving insights into the migratory properties of the injected cells.

  8. 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.

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

    Science.gov (United States)

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

    2017-04-01

    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 cells/cm 2 , 20,000 cells/cm 2 , 50,000 cells/cm 2 , and 400,000 cells/cm 2 with and without 10 or 20 ng/ml tumor necrosis factor alpha (TNFα) and 25 or 50 ng/ml interferon gamma (IFNγ). ASC-sheets formed at 400,000 cells/cm 2 after 48 h of culture. With increasing concentrations of TNFα and IFNγ, ASC-sheets with 400,000 cells/cm 2 had increased production of angiogenic factors Vascular Endothelial Growth Factor and Fibroblast Growth Factor and decreased expression of pro-inflammatory genes TNFA and Prostaglandin Synthase 2 (PTGS2) compared to lower density ASCs. Moreover, the conditioned medium of ASC-sheets with 400,000 cells/cm 2 stimulated with the low concentration of TNFα and IFNγ enhanced endothelial cell proliferation and fibroblast migration. These results suggest that a high cell density enhances ASC paracrine function might beneficial for wound repair, especially in pro-inflammatory conditions.

  10. Cytoprotection, proliferation and epidermal differentiation of adipose tissue-derived stem cells on emu oil based electrospun nanofibrous mat.

    Science.gov (United States)

    Pilehvar-Soltanahmadi, Younes; Nouri, Mohammad; Martino, Mikaël M; Fattahi, Amir; Alizadeh, Effat; Darabi, Masoud; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah

    2017-08-15

    Electrospun nanofibrous scaffolds containing natural substances with wound healing properties such as Emu oil (EO) may have a great potential for increasing the efficiency of stem cell-based skin bioengineering. For this purpose, EO blended PCL/PEG electrospun nanofibrous mats were successfully fabricated and characterized using FE-SEM, FTIR and Universal Testing Machine. The efficiency of the scaffolds in supporting the adherence, cytoprotection, proliferation and differentiation of adipose tissue-derived stem cells (ADSCs) to keratinocyte was evaluated. GC/MS and HPLC were used to determine the composition of pure EO, which revealed to be mainly fatty acids and carotenoids. FE-SEM and cell proliferation assays showed that adhesion and proliferation of ADSCs on EO-PCL/PEG nanofibers was significantly higher than on PCL/PEG nanofibers. Additionally, EO-PCL/PEG nanofibers with free radical scavenging properties conferred a cytoprotective effect against cell-damaging free radicals, while the ability to support cell adhesion and growth was maintained or even improved. Immunostaining of ADSCs on EO-PCL/PEG nanofibers confirmed the change in morphology of ADSCs from spindle to polygonal shape suggesting their differentiation toward an epidermal linage. Moreover, the expression levels of the keratin 10, filaggrin, and involucrin that are involved in epidermal differentiation were upregulated in a stage-specific manner. This preliminary study shows that EO-PCL/PEG nanofibers could be a good candidate for the fabrication of wound dressings and skin bioengineered substitutes with ADSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

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    Sebastian Gehmert

    2014-01-01

    Full Text Available Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs, these cells (ASCs provide a therapeutic option for Duchenne Muscular Dystrophy (DMD. But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases.

  12. Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration.

    Science.gov (United States)

    Rigol, Montserrat; Solanes, Núria; Farré, Jordi; Roura, Santiago; Roqué, Mercè; Berruezo, Antonio; Bellera, Neus; Novensà, Laura; Tamborero, David; Prat-Vidal, Cristina; Huzman, M A Angeles; Batlle, Montserrat; Hoefsloot, Margo; Sitges, Marta; Ramírez, José; Dantas, Ana Paula; Merino, Anna; Sanz, Ginés; Brugada, Josep; Bayés-Genís, Antoni; Heras, Magda

    2010-04-01

    Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization. (c) 2010 Elsevier Inc. All rights reserved.

  13. Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta.

    Science.gov (United States)

    Du, Wen Jing; Chi, Ying; Yang, Zhou Xin; Li, Zong Jin; Cui, Jun Jie; Song, Bao Quan; Li, Xue; Yang, Shao Guang; Han, Zhi Bo; Han, Zhong Chao

    2016-11-10

    Mesenchymal stem cells (MSCs) have been widely proven effective for therapeutic angiogenesis in ischemia animal models as well as clinical vascular diseases. Because of the invasive method, limited resources, and aging problems of adult tissue-derived MSCs, more perinatal tissue-derived MSCs have been isolated and studied as promising substitutable MSCs for cell transplantation. However, fewer studies have comparatively studied the angiogenic efficacy of MSCs derived from different tissues sources. Here, we evaluated whether the in-situ environment would affect the angiogenic potential of MSCs. We harvested MSCs from adult bone marrow (BMSCs), adipose tissue (AMSCs), perinatal umbilical cord (UMSCs), and placental chorionic villi (PMSCs), and studied their "MSC identity" by flow cytometry and in-vitro trilineage differentiation assay. Then we comparatively studied their endothelial differentiation capabilities and paracrine actions side by side in vitro. Our data showed that UMSCs and PMSCs fitted well with the minimum standard of MSCs as well as BMSCs and AMSCs. Interestingly, we found that MSCs regardless of their tissue origins could develop similar endothelial-relevant functions in vitro, including producing eNOS and uptaking ac-LDL during endothelial differentiation in spite of their feeble expression of endothelial-related genes and proteins. Additionally, we surprisingly found that BMSCs and PMSCs could directly form tubular structures in vitro on Matrigel and their conditioned medium showed significant proangiogenic bioactivities on endothelial cells in vitro compared with those of AMSCs and UMSCs. Besides, several angiogenic genes were upregulated in BMSCs and PMSCs in comparison with AMSCs and UMSCs. Moreover, enzyme-linked immunosorbent assay further confirmed that BMSCs secreted much more VEGF, and PMSCs secreted much more HGF and PGE2. Our study demonstrated the heterogeneous proangiogenic properties of MSCs derived from different tissue origins, and

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

    Science.gov (United States)

    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.

  15. Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    in the regulation of changes in key factors in WAT metabolism in response to HFD and HFD combined with exercise training. The study demonstrated that skeletal muscle derived IL-6 regulates iWAT but not eWAT metabolism. In addition, these finding showed that skeletal muscle derived IL-6 are important for the basal...... and HFD induced regulation of glucose metabolism, lipolysis and lipogenesis in iWAT, possibly through regulation of AMPK. Together these findings indicate that skeletal muscle derived IL-6 is important for basal iWAT metabolism both on chow and HFD, but only plays a minor role in exercise training......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...

  17. c-Kit-Positive Adipose Tissue-Derived Mesenchymal Stem Cells Promote the Growth and Angiogenesis of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Wenjie Li

    2017-01-01

    Full Text Available Background. Adipose tissue-derived mesenchymal stem cells (ASCs improve the regenerative ability and retention of fat grafts for breast reconstruction in cancer patients following mastectomy. However, ASCs have also been shown to promote breast cancer cell growth and metastasis. For the safety of ASC application, we aimed to identify specific markers for the subpopulation of ASCs that enhance the growth of breast cancer. Methods. ASCs and bone marrow-derived vascular endothelial progenitor cells (EPCs were isolated from Balb/c mice. c-Kit-positive (c-Kit+ or c-Kit-negative (c-Kit- ASCs were cocultured with 4T1 breast cancer cells. Orthotropic murine models of 4T1, EPCs + 4T1, and c-Kit+/-ASCs + 4T1/EPCs were established in Balb/c mice. Results. In coculture, c-Kit+ ASCs enhanced the viability and proliferation of 4T1 cells and stimulated c-Kit expression and interleukin-3 (IL-3 release. In mouse models, c-Kit+ASCs + 4T1/EPCs coinjection increased the tumor volume and vessel formation. Moreover, IL-3, stromal cell-derived factor-1, and vascular endothelial growth factor A in the c-Kit+ASCs + 4T1/EPCs coinjection group were higher than those in the 4T1, EPCs + 4T1, and c-Kit-ASCs + 4T1/EPCs groups. Conclusions. c-Kit+ ASCs may promote breast cancer growth and angiogenesis by a synergistic effect of c-Kit and IL-3. Our findings suggest that c-Kit+ subpopulations of ASCs should be eliminated in fat grafts for breast reconstruction of cancer patients following mastectomy.

  18. Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation.

    Science.gov (United States)

    Gouveia de Andrade, Ana Valéria; Bertolino, Giuliana; Riewaldt, Julia; Bieback, Karen; Karbanová, Jana; Odendahl, Marcus; Bornhäuser, Martin; Schmitz, Marc; Corbeil, Denis; Tonn, Torsten

    2015-06-01

    Recently, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have been suggested as an alternative to MSCs for the treatment of various inflammatory disorders. However, while a first case report observed beneficial therapeutic effects of repeated MSC-EV infusions in a patient with therapy-refractory graft-versus-host disease, in vitro findings revealed that MSC-EVs were significantly less immunosuppressive than their parental cells. In this study, we compared the immunosuppressive potency of MSCs derived from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs), with their secreted EVs in a standardized lymphocyte proliferation assay (LPA). Both BM-MSCs and AT-MSCs exhibited a remarkable inhibition of lymphocyte proliferation (LP) (88.1%±1.5% and 75.5%±1.5%, respectively), while isolated EVs derived from them failed to suppress LP at dose levels up to 100 μg/mL. Thus, our data further substantiate previous reports suggesting that cell-cell contact plays an important role on the immunosuppressive potential mediated by MSCs. Hence, MSC-EVs are still a matter of debate and might not be a reasonable substitute for MSCs with regard to the immunosuppressive function. Collectively, these contrasting findings may also reflect the importance of relevant translational aspects when designing new studies. Standardization of MSC culture conditions before EV collection as well as isolation and characterization methods with regard to EV purity are urged. Moreover, before clinical use, dose-finding studies evaluating MSC-EV preparations in suitable preclinical models are warranted.

  19. Update on cryopreservation of adipose tissue and adipose-derived stem cells.

    Science.gov (United States)

    Shu, Zhiquan; Gao, Dayong; Pu, Lee L Q

    2015-04-01

    This article first discusses some fundamentals of cryobiology and challenges for cell and tissue cryopreservation. Then, the results of cryopreservation of adipose cells and tissues, including adipose-derived stem cells, in the last decade are reviewed. In addition, from the viewpoint of cryobiology, some desired future work in fat cryopreservation is proposed that would benefit the optimization, standardization, and better application of such techniques. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Effect of hypothyroidism in the thyroidectomized rats on immunophenotypic characteristics and differentiation capacity of adipose tissue derived stem cells.

    Science.gov (United States)

    Simsek, T; Duruksu, G; Okçu, A; Aksoy, A; Erman, G; Utkan, Z; Cantürk, Z; Karaöz, E

    2014-01-01

    Thyroid hormones influence multiple physiological functions, like growth, differentiation, protein synthesis and metabolic rate. The hypothyroid state is a complex hormonal dysfunction rather than a single hormonal defect. The relation between hypothyroidism after thyroidectomy and stem cells is not clear. This study was designed to investigate the effect of thyroidectomy on the proliferation, telomerase enzyme activities, immunophenotypic properties and differentiation potentials of adipose tissue-derived (AT-) stem cells (SCs). AT-SCs after 60 and 120 days of thyroidectomized (Tx) rats were compared to normal rats by flow cytometry and immunocytochemistry analyses, and their telomerase activities were estimated. The telomerase activity was found to be positive for AT-SCs of Tx rats of both 60 and 120 days used in this study, but a decrease was noticed in the cells with the long-term exposure to hypothyroidism. This might indicate the decrease in the regenerative ability of the AT-SCs after 120 days of Tx compared to cells after 60 days of Tx. Both cell lines were induced to differentiate into adipogenic, osteogenic and neurogenic cell lineages, but osteogenic marker expression was not detected in the undifferentiated AT-SCs of the Tx rats. Osteogenic differentiation was also failed in stem cells derived from Tx rats, shown by Alizarin red S staining and alkaline phosphates enzyme assays. These results suggest that hypothyroidism affected SCs, altered stem cell characteristics, like telomerase activity and loss of in vitro bone formation, but not adipogenic or neurogenic differentiation ability. Hypothyroidism after Tx affects the osteogenic differentiation capacity of stem cells, which might be one of the factors of bone loss due to postnatal hypothyroidism.

  1. 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.

  2. Cholinergic and dopaminergic neuronal differentiation of human adipose tissue derived mesenchymal stem cells.

    Science.gov (United States)

    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.

  3. Proliferation of human mesenchymal stem cells derived from adipose tissue on polyurethanes with tunable biodegradability

    Directory of Open Access Journals (Sweden)

    Iaci M. Pereira

    2010-01-01

    Full Text Available Polyurethanes (PUs have been considered good candidates to be used in biomedical temporary devices that require mechanical properties comparable to soft tissues. However, toxicity of some PUs is still a concern, since these polyurethanes can contain potential toxic components and residual organic solvents derived from their synthesis. In this work, in vitro tests to measure viability and proliferation of human mesenchymal stem cells (hMSCs in contact with PUs with tunable biodegradability were performed by employing MTT, alkaline phosphatase and collagen secretion assays. PUs were produced in an aqueous environment by employing isophorone diisocyanate/hydrazine (hard segment and poly(caprolactone diol/2,2-bis (hydroxymethyl propionic acid (soft segment as the main reagents. Three series of PUs having different soft segment contents were synthesized. These PUs had their chemical structure, morphology and hydrolytic degradation investigated. The rate of hydrolysis of the obtained PUs was tailored by modifying the soft segment content of the polymers. In vitro results showed that PUs can provide a satisfactory environment for the adhesion and proliferation of hMSCs.

  4. Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models.

    Science.gov (United States)

    Shree, Nitya; Bhonde, Ramesh R

    2017-08-01

    The link between insulin resistance (IR) and type 2 diabetes has been recognized for a long time. Type 2 diabetes is often associated with basal hyperinsulinemia, reduced sensitivity to insulin, and disturbances in insulin release. There are evidences showing the reversal of IR by mesenchymal stem cells. However, the effect of conditioned media from adipose derived mesenchymal stem cells (ADSCs-CM) in reversal of IR has not been established. We established an insulin resistant model of 3T3L1 and C2C12 cells and treated with ADSCs-CM. 2-NBDG (2-[N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]Amino]-2-Deoxyglucose) uptake was performed to assess improvement in glucose uptake. Genes involved in glucose transport and in inflammation were also analysed. Western blot for glucose transporter-4 and Akt was performed to evaluate translocation of Glut4 and insulin signaling respectively. We found that the ADSCs-CM treated cells restored insulin, stimulated glucose uptake as compared to the untreated control indicating the insulin sensitizing effect of the CM. The treated cells also showed inhibition adipogenesis in 3T3L1 cells and significant reduction of intramuscular triglyceride accumulation in C2C12 cells. Gene expressions studies revealed the drastic upregulation of GLUT4 gene and significant reduction in IL6 and PAI1 gene in both 3T3L1 and C2C12 cells, indicating possible mechanism of glucose uptake with concomitant decrease in inflammation. Enhancement of GLUT4 and phospho Akt protein expression seems to be responsible for the increment in glucose uptake and enhanced insulin signaling, respectively. Our study revealed for the first time that ADSCs-CM acts as an alternative insulin sensitizer providing stem cell solution to IR. J. Cell. Biochem. 118: 2037-2043,2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Extensive characterization and comparison of endothelial cells derived from dermis and adipose tissue : Potential use in tissue engineering

    NARCIS (Netherlands)

    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

  6. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells.

    Science.gov (United States)

    Kucerova, Lucia; Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Kozovska, Zuzana

    2013-11-09

    Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Update on controls for isolation and quantification methodology of extracellular vesicles derived from adipose tissue mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Marcella eFranquesa

    2014-10-01

    Full Text Available The research field on extracellular vesicles (EV has rapidly expanded in recent years due to the therapeutic potential of EV. Adipose tissue human mesenchymal stem cells (ASC may be a suitable source for therapeutic EV.A major limitation in the field is the lack of standardization of the challenging techniques to isolate and characterize EV.The aim of our study was to incorporate new controls for the detection and quantification of EV derived from ASC and analyze the applicability and limitations of the available techniques.ASC were cultured in medium supplemented with 5% of vesicles-free fetal bovine serum. The EV were isolated from Conditioned Medium by differential centrifugation with size filtration (0.2 µm. As a control, non-conditioned culture medium was used (Control Medium. To detect EV, electron microscopy, conventional flow cytometry and Western Blot were used. The quantification of the EV was by total protein quantification, Exo-ELISA immunoassay, and Nanosight. Cytokines and growth factors in the EV samples were measured by Multiplex Bead Array Kit. The EV were detected by electron microscope. Total protein measurement was not useful to quantify EV as the Control Medium showed similar protein contents as the EV samples. The Exo-ELISA kits had technical troubles and it was not possible to quantify the concentration of exosomes in the samples. The use of Nanosight enabled quantification and size determination of the EV. It is however not possible to distinguish protein aggregates from EV with this method. The technologies for quantification and characterization of the EV need to be improved. In addition, we detected protein contaminants in the EV samples, which make it difficult to determine the real effect of EV in experimental models. It will be crucial in the future to optimize design novel methods for purification and characterization of EV.

  10. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Kucerova, Lucia; Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Kozovska, Zuzana

    2013-01-01

    Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses

  11. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    Directory of Open Access Journals (Sweden)

    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  12. Adipogenic Impairment of Adipose Tissue-Derived Mesenchymal Stem Cells in Subjects With Metabolic Syndrome: Possible Protective Role of FGF2.

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    Oliva-Olivera, Wilfredo; Coín-Aragüez, Leticia; Lhamyani, Said; Clemente-Postigo, Mercedes; Torres, Juan Alcaide; Bernal-López, Maria Rosa; El Bekay, Rajaa; Tinahones, Francisco José

    2017-02-01

    The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome. The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles. This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. University Hospital. Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study. ASCs were obtained from both visceral and subcutaneous adipose tissue. Adipogenic, fibrotic gene expression was quantified by quantitative polymerase chain reaction; Smad7 and fibroblast growth factor 2 were quantified by western blotting and enzyme-linked immunosorbent assay, respectively. The susceptibility of ASCs to apoptosis, their population doubling time, and their clonogenic potential were evaluated. The worsening metabolic profile of the patients was accompanied by a decrease in the intrinsic levels of adipogenic gene expression, reduced proliferation rate, clonogenic potential, and exportation of fibroblast growth factor 2 to the cell surface of the ASCs derived from both tissues. In addition, the ASCs from patients without metabolic syndrome showed differences in susceptibility to apoptosis and expression of TGFβ-signaling inhibitory protein Smad7 with respect to the ASCs from patients with metabolic syndrome. Our results suggest that the decrease in adipogenic-gene mRNA and clonogenic potential, as well as the accumulation of fibrotic proteins with metabolic alterations, could be a relevant mechanism controlling the number and size of neogenerated adipocytes and involved in alteration of adipose-tissue expansion. Copyright © 2017 by the Endocrine Society

  13. 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.

  14. 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.

  15. New Insights into the Role of Macrophages in Adipose Tissue Inflammation and Fatty Liver Disease: Modulation by Endogenous Omega-3 Fatty Acid-derived Lipid Mediators

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    Joan eClària

    2011-10-01

    Full Text Available Obesity is causally linked to a chronic state of low-grade inflammation in adipose tissue. Prolonged, unremitting inflammation in this tissue has a direct impact on insulin-sensitive tissues (i.e. liver and its timely resolution is a critical step toward reducing the prevalence of related co-morbidities such as insulin resistance and non-alcoholic fatty liver disease. This article describes the current state-of-the-art knowledge and novel insights into the role of macrophages in adipose tissue inflammation, with special emphasis on the progressive changes in macrophage polarization observed over the course of obesity. In addition, this article extends the discussion to the contribution of Kupffer cells, the liver resident macrophages, to metabolic liver disease. Special attention is given to the modulation of macrophage responses by omega-3-PUFAs, and more importantly by resolvins, which are potent anti-inflammatory and pro-resolving autacoids generated from docosahexaenoic and eicosapentaenoic acids. In fact, resolvins have been shown to work as endogenous stop signals in inflamed adipose tissue and to return this tissue to homeostasis by inducing a phenotypic switch in macrophage polarization toward a pro-resolving phenotype. Collectively, this article offers new views on the role of macrophages in metabolic disease and their modulation by endogenously-generated omega-3-PUFA-derived lipid mediators.

  16. Adipose tissue-derived stem cells in combination with xanthan gum attenuate osteoarthritis progression in an experimental rat model.

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    Mei, Li; Shen, Bojiang; Xue, Jiajun; Liu, Shaoying; Ma, Aibin; Liu, Fuyan; Shao, Huarong; Chen, Jianying; Chen, Qixin; Liu, Fei; Ying, Yong; Ling, Peixue

    2017-12-09

    The current study explored the efficacy of an intra-articular (IA) injection of allogeneic adipose tissue-derived stem cells (ADSCs) combined with xanthan gum (XG) in a rat osteoarthritis (OA) model. We confirmed that XG significantly inproved proliferation of ADSCs in a dose dependent manner in vitro. The rat OA model was induced by an anterior cruciate ligament transection (ACLT), and at 4 weeks after surgery, rats were divided into four groups: the XG-ADSCs group, the ADSCs group, the XG group and the phosphate-buffered saline (PBS) group. A single dose of 1 × 10 6 allogeneic ADSCs suspended in 1% XG, ADSCs suspended in PBS, 1% XG alone or PBS alone was injected into the OA joint of rats in the respective treatment groups. Rats were sacrificed at 8 weeks after surgery. Treatment outcomes were evaluated by weight-bearing control of the hind limbs, gross morphological analysis, histological analysis and specific staining of articular cartilage, and measurement of inflammatory factors in synovial fluid. For the rats in the XG-ADSC-s and ADSCs-treated groups, the weight-bearing percentage of the right hind limb was significantly increased compared to that in the PBS group and was sustained over 4 weeks. However, the positive effect in the XG-ADSCs group was significantly greater than that in the ADSCs group. For the rats in the XG group, the efficacy decreased during the third week after surgery. The articular cartilage was relatively normal in the XG-ADSCs group, and moderate degeneration was observed in the ADSCs and XG groups. ADSCs and XG-ADSC treatments significantly decreased the concentrations of IL-1β, TNF-α, MMP-3 and MMP-13 in synovial fluid; however, the attenuating effect of the XG-ADSCs treatment was significantly enhanced compared with that of the ADSCs treatment alone. These results indicate that a single IA injection of allogeneic ADSCs combined with XG efficiently attenuated OA progression with a therapeutic effect that was significantly

  17. Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue.

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    Saleh Heneidi

    Full Text Available Advances in stem cell therapy face major clinical limitations, particularly challenged by low rates of post-transplant cell survival. Hostile host factors of the engraftment microenvironment such as hypoxia, nutrition deprivation, pro-inflammatory cytokines, and reactive oxygen species can each contribute to unwanted differentiation or apoptosis. In this report, we describe the isolation and characterization of a new population of adipose tissue (AT derived pluripotent stem cells, termed Multilineage Differentiating Stress-Enduring (Muse Cells, which are isolated using severe cellular stress conditions, including long-term exposure to the proteolytic enzyme collagenase, serum deprivation, low temperatures and hypoxia. Under these conditions, a highly purified population of Muse-AT cells is isolated without the utilization of cell sorting methods. Muse-AT cells grow in suspension as cell spheres reminiscent of embryonic stem cell clusters. Muse-AT cells are positive for the pluripotency markers SSEA3, TR-1-60, Oct3/4, Nanog and Sox2, and can spontaneously differentiate into mesenchymal, endodermal and ectodermal cell lineages with an efficiency of 23%, 20% and 22%, respectively. When using specific differentiation media, differentiation efficiency is greatly enhanced in Muse-AT cells (82% for mesenchymal, 75% for endodermal and 78% for ectodermal. When compared to adipose stem cells (ASCs, microarray data indicate a substantial up-regulation of Sox2, Oct3/4, and Rex1. Muse-ATs also exhibit gene expression patterns associated with the down-regulation of genes involved in cell death and survival, embryonic development, DNA replication and repair, cell cycle and potential factors related to oncogenecity. Gene expression analysis indicates that Muse-ATs and ASCs are mesenchymal in origin; however, Muse-ATs also express numerous lymphocytic and hematopoietic genes, such as CCR1 and CXCL2, encoding chemokine receptors and ligands involved in stem cell

  18. Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model.

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    Li Mei

    Full Text Available Mesenchymal stem cell (MSC-based cell therapy is a promising avenue for osteoarthritis (OA treatment. In the present study, we evaluated the efficacy of intra-articular injections of culture-expanded allogenic adipose tissue-derived stem cells (ADSCs for the treatment of anterior cruciate ligament transection (ACLT induced rat OA model. The paracrine effects of major histocompatibility complex (MHC-unmatched ADSCs on chondrocytes were investigated in vitro. Rats were divided into an OA group that underwent ACLT surgery and a sham-operated group that did not undergo ACLT surgery. Four weeks after surgery mild OA was induced in the OA group. Subsequently, the OA rats were randomly divided into ADSC and control groups. A single dose of 1 × 106 ADSCs suspended in 60 μL phosphate-buffered saline (PBS was intra-articularly injected into the rats of the ADSC group. The control group received only 60 μL PBS. OA progression was evaluated macroscopically and histologically at 8 and 12 weeks after surgery. ADSC treatment did not cause any adverse local or systemic reactions. The degeneration of articular cartilage was significantly weaker in the ADSC group compared to that in the control group at both 8 and 12 weeks. Chondrocytes were co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1β-induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and MMP-13 and the pro-inflammatory cytokines TNF-α and IL-6 in chondrocytes. Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL-10 in chondrocytes. The results of this study indicated that the intra-articular injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration in an experimental rat OA model without inducing any adverse reactions. MHC-unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage. The paracrine effects

  19. Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model.

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    Mei, Li; Shen, Bojiang; Ling, Peixue; Liu, Shaoying; Xue, Jiajun; Liu, Fuyan; Shao, Huarong; Chen, Jianying; Ma, Aibin; Liu, Xia

    2017-01-01

    Mesenchymal stem cell (MSC)-based cell therapy is a promising avenue for osteoarthritis (OA) treatment. In the present study, we evaluated the efficacy of intra-articular injections of culture-expanded allogenic adipose tissue-derived stem cells (ADSCs) for the treatment of anterior cruciate ligament transection (ACLT) induced rat OA model. The paracrine effects of major histocompatibility complex (MHC)-unmatched ADSCs on chondrocytes were investigated in vitro. Rats were divided into an OA group that underwent ACLT surgery and a sham-operated group that did not undergo ACLT surgery. Four weeks after surgery mild OA was induced in the OA group. Subsequently, the OA rats were randomly divided into ADSC and control groups. A single dose of 1 × 106 ADSCs suspended in 60 μL phosphate-buffered saline (PBS) was intra-articularly injected into the rats of the ADSC group. The control group received only 60 μL PBS. OA progression was evaluated macroscopically and histologically at 8 and 12 weeks after surgery. ADSC treatment did not cause any adverse local or systemic reactions. The degeneration of articular cartilage was significantly weaker in the ADSC group compared to that in the control group at both 8 and 12 weeks. Chondrocytes were co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1β-induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and MMP-13 and the pro-inflammatory cytokines TNF-α and IL-6 in chondrocytes. Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL-10 in chondrocytes. The results of this study indicated that the intra-articular injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration in an experimental rat OA model without inducing any adverse reactions. MHC-unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage. The paracrine effects of ADSCs on

  20. Adipose Tissue Remodeling as Homeostatic Inflammation

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    Michiko Itoh

    2011-01-01

    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  1. The regulation of adipose tissue distribution in humans.

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    Björntorp, P

    1996-04-01

    The regulation of adipose tissue distribution is an important problem in view of the close epidemiological and metabolic associations between centralized fat accumulation and disease. With visceral fat accumulation multiple endocrine perturbations are found, including elevated cortisol and androgens in women, as well as low growth hormone (GH) and, in men, testosterone (T) secretion. These abnormalities probably derive from a hypersensitive hypothalamo-pituitary-adrenal axis, with hyperinsulinemia related to a marked insulin resistance as a consequence. These hormonal changes exert profound effects on adipose tissue metabolism and distribution. At the adipocyte level cortisol and insulin promote lipid accumulation by expressing lipoprotein lipase activity, while T, GH and probably estrogens exert opposite effects. The consequences will most likely be more expressed in visceral than subcutaneous adipose tissues because of a higher cellularity, innervation and blood flow. Furthermore, the density of cortisol and androgen receptors seems to be higher in this than other adipose tissue regions. The endocrine perturbations found in visceral obesity with an abundance of the lipid accumulating hormones cortisol and insulin, and a relatively low secretion of the lipid mobilizing sex steroid hormones and GH would therefore be expected to be followed by visceral fat accumulation. The potential significance of local synthesis of steroid hormones in adipose tissue requires more attention. Although studies in vitro are informative when elucidating detailed mechanisms of hormonal interactions, they might not give a true picture of the regional integrated regulation of adipose tissue lipid storage and mobilization. Such information can be obtained by regional measurements of lipid mobilization by free fatty acid turnover or by microdialysis techniques, both showing lower rates of mobilization in leg than in upper body adipose tissues. More detailed information can be obtained by

  2. Platelet-Derived Growth Factor Receptor-Positive Pericytic Cells of White Adipose Tissue from Critical Limb Ischemia Patients Display Mesenchymal Stem Cell-Like Properties.

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    Kim, Eo Jin; Seo, Sang Gyo; Shin, Hyuk Soo; Lee, Doo Jae; Kim, Ji Hye; Lee, Dong Yeon

    2017-06-01

    The pericytes in the blood vessel wall have recently been identified to be important in regulating vascular formation, stabilization, remodeling, and function. We isolated and identified pericyte-like platelet-derived growth factor receptor beta-positive (PDGFRβ+) cells from the stromal vascular fraction (SVF) of adipose tissue from critical limb ischemia (CLI) patients and investigated their potential as a reliable source of stem cells for cell-based therapy. De-identified subcutaneous fat tissues were harvested after amputation in CLI patients. Freshly isolated SVF cells and culture-expanded adipose-derived stem cells (ADSCs) were quantified using flow cytometry. A matrigel tube formation assay and multi-lineage differentiation were performed to assess pericytic and mesenchymal stem cell (MSC)-like characteristics of PDGFRβ+ ADSCs. PDGFRβ+ cells were located in the pericytic area of various sizes of blood vessels and coexpressed mesenchymal stem cell markers. PDGFRβ+ cells in freshly isolated SVF cells expressed a higher level of stem cell markers (CD34 and CXCR4) and mesenchymal markers (CD13, CD44, CD54, and CD90) than PDGFRβ- cells. In vitro expansion of PDGFRβ+ cells resulted in enrichment of the perivascular mesenchymal stem-like (PDGFRβ+/CD90+/CD45-/CD31-) cell fractions. The Matrigel tube formation assay revealed that PDGFRβ+ cells were located in the peritubular area. PDGFRβ+ ADSCs cells demonstrated a good multilineage differentiation potential. Pericyte-like PDGFRβ+ cells from the SVF of adipose tissue from CLI patients had MSC-like characteristics and could be amplified by in vitro culture with preservation of their cell characteristics. We believe PDGFRβ+ cells in the SVF of adipose tissue can be used as a reliable source of stem cells even in CLI patients.

  3. Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue-Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration-Approved Nerve Conduit.

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    Klein, Silvan M; Vykoukal, Jody; Li, De-Pei; Pan, Hui-Lin; Zeitler, Katharina; Alt, Eckhard; Geis, Sebastian; Felthaus, Oliver; Prantl, Lukas

    2016-07-01

    Conduits preseeded with either Schwann cells or stem cells differentiated into Schwann cells demonstrated promising results for the outcome of nerve regeneration in nerve defects. The concept of this trial combines nerve repair by means of a commercially available nerve guidance conduit and preseeding with autologous, undifferentiated, adipose tissue-derived stem cells. Adipose tissue-derived stem cells were harvested from rats and subsequently seeded onto a U.S. Food and Drug Administration-approved type I collagen conduit. Sciatic nerve gaps 10 mm in length were created, and nerve repair was performed by the transplantation of either conduits preseeded with autologous adipose tissue-derived stem cells or acellular (control group) conduits. After 6 months, the motor and sensory nerve conduction velocity were assessed. Nerves were removed and examined by hematoxylin and eosin, van Gieson, and immunohistochemistry (S100 protein) staining for the quality of axonal regeneration. Nerve gaps treated with adipose tissue-derived stem cells showed superior nerve regeneration, reflected by higher motor and sensory nerve conduction velocity values. The motor and sensory nerve conduction velocity were significantly greater in nerves treated with conduits preseeded with adipose tissue-derived stem cells than in nerves treated with conduits alone (p adipose tissue-derived stem cell group. In this group, axon arrangement inside the conduits was more organized. Transplantation of adipose tissue-derived stem cells significantly improves motor and sensory nerve conduction velocity in peripheral nerve gaps. Preseeded conduits showed a more organized axon arrangement inside the conduit in comparison with nerve conduits alone. The approach used here could readily be translated into a clinical therapy. Therapeutic, V.

  4. 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.

  5. 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.

  6. 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.

  7. 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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    Ha, Ki-Young; Park, Hojin; Park, Seung-Ha; Lee, Byung-Il; Ji, Yi-Hwa; Kim, Tae-Yeon; Yoon, Eul-Sik

    2015-11-01

    The 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. Adipose 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. In 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. ASCs 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.

  8. Reconstruction of epidural fat with engineered adipose tissue from adipose derived stem cells and PLGA in the rabbit dorsal laminectomy model.

    Science.gov (United States)

    Xu, Jianli; Chen, Yingchun; Yue, Yunlong; Sun, Jian; Cui, Lei

    2012-10-01

    Epidural fibrosis resulted from epidural fat destruction following laminectomy operation is regarded as a main cause of failed back surgery syndrome, which represents one of the most common complications in spine surgery. Up to now, the effectiveness of currently available treatments to prevent such a syndrome is quite limited. In the present study, we aimed to restore epidural fat using adipose tissue engineered from adipose derived stem cells (ASCs) in a rabbit dorsal laminectomy model. ASCs isolated from subcutaneous fat were first expanded to passage 3, seeded on porous poly(lactic-co-glycolic acid, PLGA) scaffold and then adipogenically induced for 7 days in vitro to form cell-scaffold complex. Laminectomy sites were created at T13-L1 level in each animal. The laminectomy defect was implanted either with cell-scaffold complex or PLGA scaffold alone. Non-treated defect was also included as a control. The animals were subjected to MRI evaluation at 1, 12 and 24 weeks post-surgery, and sacrificed at 24 weeks for gross and histological observation. It was demonstrated by MRI evaluation that scar tissue of coarse and high density was formed within laminectomy site in PLGA alone and non-treated groups as early as 12 weeks. However, the defect implanted with engineered adipose had formed a continuous linear adipose tissue regenerated along the spinal cord at 24 weeks. Histologically, a distinct area of adipose tissue just overlaying the dura mater could be identified in cell-scaffold complex treated group at 24 weeks post-operation. Regeneration of epidural fat was further confirmed by positive Oil Red O staining. As to the defect treated with PLGA alone or left untreated, either fine or dense scar tissue adhering to the dura mater was observed. Moreover, we could track the implanted ASCs labeled by magnetic nanoparticles within epidural area for as long as four weeks by MRI detection. Thus, adipose tissue engineered from ASCs exhibited great potential in restoration

  9. Subcutaneous adipose tissue classification

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    A. Sbarbati

    2010-11-01

    Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for

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

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    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

    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. Simultaneous expression profiles of miRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and LC-MS/MS proteomic analysis in porcine MSCs and their daughter EVs (n = 3 each). TargetScan and ComiR were used to predict miRNA target genes. Functional annotation analysis was performed using DAVID 6.7 database to rank primary gene ontology categories for the enriched mRNAs, miRNA target genes, and proteins. STRING was used to predict associations between mRNA and miRNA target genes. Differential expression analysis revealed 4 miRNAs, 255 mRNAs, and 277 proteins enriched in EVs versus MSCs (fold change >2, pextracellular matrix remodeling, blood coagulation, inflammation, and angiogenesis. Porcine MSC-derived EVs contain a genetic cargo of miRNAs and mRNAs that collectively control TF activity in EVs and recipient cells, as well as proteins capable of modulating cellular pathways linked to tissue repair. These properties provide the fundamental basis for considering therapeutic use of EVs in tissue regeneration.

  11. Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

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    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.

  12. 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 ...

  13. 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

  14. Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging

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    Giuliana Di Rocco

    2011-01-01

    Full Text Available Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1 at the wound site. Adipose tissue-associated stromal cells (AT-SCs can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production.

  15. Comparative analysis of human UCB and adipose tissue derived mesenchymal stem cells for their differentiation potential into brown and white adipocytes.

    Science.gov (United States)

    Rashnonejad, Afrooz; Ercan, Gulinnaz; Gunduz, Cumhur; Akdemir, Ali; Tiftikcioglu, Yigit Ozer

    2018-02-16

    The differentiation potential of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) into brown and white adipocytes in comparison to Adipose tissue derived MSCs (AD-MSCs) were investigated in order to characterize their potency for future cell therapies. MSCs were isolated from ten UCB samples and six liposuction materials. MSCs were differentiated into white and brown adipocytes after characterization by flow cytometry. Differentiated adipocytes were stained with Oil Red O and hematoxylin/eosin. The UCP1 protein levels in brown adipocytes were investigated by immunofluoresence and western blot analysis. Cells that expressed mesenchymal stem cells markers (CD34-, CD45-, CD90+ and CD105+) were successfully isolated from UCB and adipose tissue. Oil Red O staining demonstrated that white and brown adipocytes obtained from AD-MSCs showed 85 and 61% of red pixels, while it was 3 and 1.9%, respectively for white and brown adipocytes obtained from UCB-MSCs. Fluorescence microscopy analysis showed strong uncoupling protein 1 (UCP1) signaling in brown adipocytes, especially which were obtained from AD-MSCs. Quantification of UCP1 protein amount showed 4- and 10.64-fold increase in UCP1 contents of brown adipocytes derived from UCB-MSCs and AD-MSCs, respectively in comparison to undifferentiated MSCs (P stem cell type to be differentiated into these cell types. In contrast, high differentiation efficiency of AD-MSCs into brown and white adipocytes make it appropriate stem cell type to use in future regenerative medicine of soft tissue disorders or fighting with obesity and its related disorders.

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

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    Alfonso Eirin

    Full Text Available 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.Simultaneous expression profiles of miRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and LC-MS/MS proteomic analysis in porcine MSCs and their daughter EVs (n = 3 each. TargetScan and ComiR were used to predict miRNA target genes. Functional annotation analysis was performed using DAVID 6.7 database to rank primary gene ontology categories for the enriched mRNAs, miRNA target genes, and proteins. STRING was used to predict associations between mRNA and miRNA target genes.Differential expression analysis revealed 4 miRNAs, 255 mRNAs, and 277 proteins enriched in EVs versus MSCs (fold change >2, p<0.05. EV-enriched miRNAs target transcription factors (TFs and EV-enriched mRNAs encode TFs, but TF proteins are not enriched in EVs. Rather, EVs are enriched for proteins that support extracellular matrix remodeling, blood coagulation, inflammation, and angiogenesis.Porcine MSC-derived EVs contain a genetic cargo of miRNAs and mRNAs that collectively control TF activity in EVs and recipient cells, as well as proteins capable of modulating cellular pathways linked to tissue repair. These properties provide the fundamental basis for considering therapeutic use of EVs in tissue regeneration.

  17. NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells.

    Science.gov (United States)

    Pitrone, Maria; Pizzolanti, Giuseppe; Tomasello, Laura; Coppola, Antonina; Morini, Lorenzo; Pantuso, Gianni; Ficarella, Romina; Guarnotta, Valentina; Perrini, Sebastio; Giorgino, Francesco; Giordano, Carla

    2017-05-23

    The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 ± 5 and 30 ± 5 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90, CD105, CD29, CD31, CD45 and CD146 were analyzed by flow cytometry, and the stem cell transcription factors NANOG, SOX2 and OCT4 were detected by immunoblotting and real-time PCR. NANOG , SOX2 and OCT4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT4. NANOG silencing induced a significant OCT4 (70 ± 0.05%) and SOX2 (75 ± 0.03%) downregulation, whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency.

  18. Comparison of human mesenchymal stem cells derived from dental pulp, bone marrow, adipose tissue, and umbilical cord tissue by gene expression.

    Science.gov (United States)

    Stanko, Peter; Kaiserova, Katarina; Altanerova, Veronika; Altaner, Cestmir

    2014-09-01

    Our aims were to characterize human mesenchymal stem cells isolated from various tissues by pluripotent stem cells gene expression profile. Four strains of dental pulp stem cells (DP-MSCs) were isolated from dental pulp tissue fragments adhered to plastic tissue culture dishes. Mesenchymal stem cells derived from umbilical cord tissue (UBC-MSCs) were isolated with the same technique. Bone marrow derived mesenchymal stem cells (BM-MSCs) were isolated from nucleated cells of bone marrow obtained by density gradient centrifugation. Human mesenchymal stem cells from adipose tissue (AT-MSCs) were isolated by collagenase digestion. All kinds of MSCs used in this study were cultivated in low glucose DMEM containing 5% or human platelet extract. All stem cell manipulation was performed in GMP conditions. Expression of 15 pluripotent stem cells genes on the level of proteins was measured by Proteome Profiler Human Pluripotent Stem Cell Array. Induction of MSCs to in vitro differentiation to adipocytes, osteoblasts, chondroblasts was achieved by cultivation of cells in appropriate differentiation medium. All MSCs tested were phenotypically similar and of fibroblastoid morphology. DP-MSCs and UBC-MSCs were more proliferative than bone marrow BM-MSCs and AT-MSCs. Protein expression of 15 genes typical for pluripotent stem cells distinguished them into two groups. While the gene expression profiles of BM-MSC, AT-MSCs and UBC-MSCs were similar, DP-MSCS differed in relative gene expression on the level of their products in several genes. Dental pulp mesenchymal stem cells cultivated in vitro under the same conditions as MSCs from bone marrow, adipose tissue and umbilical cord tissue can be distinguished by pluripotent stem cell gene expression profile.

  19. [HUMAN ADIPOSE-DERIVED STEM CELLS COMBINED WITH SMALL INTESNITAL SUBMUCOSA POWDER/CHITOSAN CHLORIDE-β-GLYCEROL PHOSPHATE DISODIUM-HYDROXYETHYL CELLULOSE HYBRID FOR ADIPOSE TISSUE ENGINEERING].

    Science.gov (United States)

    Zhang, Shu; Luo, Jingcong; Lü, Qing; Deng, Xueqin; Xiong, Bingjun

    2015-08-01

    To study the feasibility of human adipose-derived stem cells (hADSCs) combined with small intestinal submucosa powder (SISP)/chitosan chloride (CSCl)-β-glycerol phosphate disodium (GP)-hydroxyethyl cellulose (HEC) for adipose tissue engineering. hADSCs were isolated from human breast fat with collagenase type I digestion, and the third passage hADSCs were mixed with SISP/CSCl-GP-HEC at a density of 1 x 10(6) cells/mL. Twenty-four healthy female nude mice of 5 weeks old were randomly divided into experimental group (n = 12) and control group (n=12), and the mice were subcutaneously injected with 1 mL hADSCs+SISP/CSCl-GP-HEC or SISP/CSCl-GP-HEC respectively at the neck. The degradation rate was evaluated by implant volume measurement at 0, 1, 2, 4, and 8 weeks. Three mice were euthanized at 1, 2, 4, and 8 weeks respectively for general, histological, and immunohistochemical observations. The ability of adipogenesis (Oil O staining), angiopoiesis (CD31), and localized the hADSCs (immunostaining for human Vimentin) were identified. The volume of implants of both groups decreased with time, but it was greater in experimental group than the control group, showing significant difference at 8 weeks (t = 3.348, P = 0.029). The general observation showed that the border of implants was clear with no adhesion at each time point; fat-liked new tissues were observed with capillaries on the surface at 8 weeks in 2 groups. The histological examinations showed that the structure of implants got compact gradually after injection, and SISP gradually degraded with slower degradation speed in experimental group; adipose tissue began to form, and some mature adipose tissue was observed at 8 weeks in the experimental group. The Oil O staining positive area of experimental group was greater than that of the control group at each time point, showing significant difference at 8 weeks (t = 3.41 1, P = 0.027). Immunohistochemical staining for Vemintin showed that hADSCs could survive at

  20. USE OF AUTOLOGOUS ADIPOSE TISSUE DERIVED STROMAL VASCULAR FRACTION IN TREATMENT OF KNEE OSTEOARTHRITIS AND CHONDRAL LESIONS

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    Vinay

    2015-10-01

    Full Text Available Osteoarthritis is a joint inflammation that results from cartilage degeneration. It can be caused by aging, heredity and injury from trauma or disease. Stromal vascular fraction (SVF, containing large amount of stem cells and other regenerative cells, can be easily obtained from loose connective tissue that is associated with adipose tissue. Here we evaluated safety and clinical efficacy of freshly isolated autologous SVF cells in patients with grade 2 - 4 degenerative osteoarthritis (OA. A total of 31 patients underwent standard liposuction under local anesthesia and SVF cells were isolated and prepared for application into joints. A total of 61 joints, mainly knee and hip joints, were treated with a single dose of SVF cells. 19 patients were fol lowed for minimum 6 weeks for safety and efficacy. Modified KOOS Clinical Score was used to evaluate clinical effect and was based on pain, non - steroid analgesic usage, limping, extent of joint movement, and stiffness evaluation before and at pre - operative , 1 week post - op, 1 month and 6 weeks after the treatment. No serious side effects, systemic infection or cancer was associated with SVF cell therapy. All patients improved after the treatment. Average KOOS score improved from pre - operative 37.5 to post - op erative 6 week average 66.6. All sub scale parameter for pain, symptoms, activity of living & quality of life are also improved. Higher grade of OA were associated with slower healing. In conclusion, here we report a novel and promising treatment approach for patients with degenerative OA that is safe, cost - effective, and relying only on autologous cells, and can be used as one of the minimal invasive treatment modality for osteoarthritis

  1. 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.

    Science.gov (United States)

    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.

  2. Telomerase reverse transcriptase genetically modified adipose tissue derived stem cells improves erectile dysfunction by inhibiting oxidative stress and enhancing proliferation in rat model.

    Science.gov (United States)

    Wu, Xiao-Jun; Shen, Wen-Hao; He, Peng; Zhou, Xiao-Zhou; Zhi, Yi; Dai, Qiang; Chen, Zhi-Wen; Zhou, Zhan-Song

    2017-08-01

    Erectile dysfunction (ED) is considered to be incapable of obtaining or/and keeping a sufficient erection function to receive the satisfactory during the sexual intercourse. This study aims to investigate the effects of telomerase reverse transcriptase (hTERT) modified adipose tissue derived stem cells (ADSCs) autologously injected into cavernosa of the ED rats on erectile function. The ADSCs were isolated form the rat subcutaneous adipose tissue sample, and identified by examining the CD29 and CD44 molecule. The ED model was established by using 100μg/kg apomorphine (APO). The adenovirus expressing rat hTERT (Ade-hTERT vector) was established, and transfected into ADSCs and injected into ED rat model, respectively. Telomerase activity, cell growth, cell apoptosis were analyzed by using TRAP ELISA assay, CCK8 assay and flow cytometry assay, respectively. The trophic growth factors were examined by using enzyme-linked immunosorbent assay (ELISA). The mRNA and proteins were detected by using semi-quantitative PCR and western blot assay, respectively. Ade-hTERT vector was highly expressed in both ADSCs and ED rat mode. The hTERT expression enhanced the telomerase activity, inhibits cell apoptosis and enhances proliferation of ADSCs (P<0.05). hTERT expression triggers the secretory function of ADSCs and induces differentiative potential of ADSCs. hTERT expression inhibits apoptosis and increases eNOS and nNOS levels in older ED rats compared to the Ade-vector injected ED rats (P<0.05). In conclusion, the hTERT modification could enhance the ADSCs proliferation, and hTERT modified ADSCs could increase the anti-oxidative stress capacity in the ED rat model. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

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    Pak Jaewoo

    2011-07-01

    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  4. 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

  5. Comparative Study Between Mesenchymal Stem Cells Derived from Bone Marrow and from Adipose Tissue, Associated with Xenograft, in Appositional Reconstructions: Histomorphometric Study in Rabbit Calvaria.

    Science.gov (United States)

    Coelho de Faria, Andrea Baptista; Chiantia, Fernando Biolcati; Teixeira, Marcelo Lucchesi; Aloise, Antonio Carlos; Pelegrine, André Antonio

    This study analyzed the use of bone marrow-derived mesenchymal stem cells and adipose tissue-derived stem cells, associated with xenograft, in appositional reconstructions in rabbit calvaria using histomorphometry. Fifteen New Zealand rabbits, weighing 3.5 to 4.0 kg and aged between 10 and 12 months, were randomly divided into three groups. Appositional bone reconstruction situations were created in the calvaria of the animals using titanium cylinders, fitted with titanium occlusive caps. Bone decortication was performed to promote bleeding. Inside the cylinders, only xenograft was positioned in the control group (CG; n = 5); xenograft combined with mesenchymal bone marrow-derived stem cells was positioned in group 1 (G1; n = 5), and a xenograft combined with adult mesenchymal stem cells derived from adipose tissue was positioned in group 2 (G2; n = 5). After 56 days, all rabbits were euthanized and their parietal bones processed for histomorphometric analysis, and the following parameters were evaluated: newly formed bone; residual graft particles; soft tissue; vital bone titanium contact, also called the level of osseointegration; and the level of bone volume contained inside the cylinders, also called the internal bone volume. The histomorphometric study revealed the following for CG, G1, and G2: newly formed bone of 18.96% ± 9.00%, 27.88% ± 9.98%, and 22.32% ± 7.45%; residual graft particles of 28.43% ± 2.44%, 23.31% ± 3.11%, and 27.58% ± 3.98%; soft tissue of 52.61% ± 10.80%, 50.23% ± 8.72%, and 49.90% ± 8.76%; vital bone titanium contact of 4.98% ± 4.30%, 34.91% ± 7.82%, and 20.87% ± 5.43%; and internal bone volume of 88.36% ± 25.97%, 98.73% ± 19.05%, and 98.52% ± 19.87%, respectively. No statistical difference between groups for newly formed bone, residual graft particles, soft tissue, and internal bone volume (P > .05) were verified. Regarding vital bone titanium contact, it was observed that the use of bone marrow mesenchymal stem cells

  6. The endocrine function of adipose tissue

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    Wagner de Jesus Pinto

    2014-09-01

    Full Text Available Currently it is considered the adipose tissue as a dynamic structure involved in many physiological and metabolic processes, produces and releases a variety of active peptides known by the generic name of adipokines that act performing endocrine, paracrine and autocrine. Furthermore, numbers expressed receptors that respond allows the afferent signals from endocrine organs, and also central nervous system. In 1987, the adipose tissue has been identified as the major site of metabolism of steroid hormones, thereafter, in 1994, it was recognized as an endocrine organ and the leptin being an early secretory products identified. In addition other biologically active substances were being isolated, such as adiponectin, resistin, TNF-a, interleukin-6 and others. The adipokines derived from adipose tissue modulate many metabolic parameters such as control of food intake, energy balance and peripheral insulin sensitivity, for example. Thus, the altered secretion of adipokines by adipose tissue may have metabolic effects may present complex relations with the pathophysiological process of obesity, endothelial dysfunction, inflammation, atherosclerosis and Diabetes mellitus. The understanding of the molecular processes occurring in the adipocytes may provide new tools for the treatment of pathophysiological conditions such as, for example, metabolic syndrome, obesity and diabetes mellitus.

  7. Derivation and validation of simple anthropometric equations to predict adipose tissue mass and total fat mass with MRI as the reference method.

    Science.gov (United States)

    Al-Gindan, Yasmin Y; Hankey, Catherine R; Govan, Lindsay; Gallagher, Dympna; Heymsfield, Steven B; Lean, Michael E J

    2015-12-14

    The reference organ-level body composition measurement method is MRI. Practical estimations of total adipose tissue mass (TATM), total adipose tissue fat mass (TATFM) and total body fat are valuable for epidemiology, but validated prediction equations based on MRI are not currently available. We aimed to derive and validate new anthropometric equations to estimate MRI-measured TATM/TATFM/total body fat and compare them with existing prediction equations using older methods. The derivation sample included 416 participants (222 women), aged between 18 and 88 years with BMI between 15·9 and 40·8 (kg/m2). The validation sample included 204 participants (110 women), aged between 18 and 86 years with BMI between 15·7 and 36·4 (kg/m2). Both samples included mixed ethnic/racial groups. All the participants underwent whole-body MRI to quantify TATM (dependent variable) and anthropometry (independent variables). Prediction equations developed using stepwise multiple regression were further investigated for agreement and bias before validation in separate data sets. Simplest equations with optimal R (2) and Bland-Altman plots demonstrated good agreement without bias in the validation analyses: men: TATM (kg)=0·198 weight (kg)+0·478 waist (cm)-0·147 height (cm)-12·8 (validation: R 2 0·79, CV=20 %, standard error of the estimate (SEE)=3·8 kg) and women: TATM (kg)=0·789 weight (kg)+0·0786 age (years)-0·342 height (cm)+24·5 (validation: R (2) 0·84, CV=13 %, SEE=3·0 kg). Published anthropometric prediction equations, based on MRI and computed tomographic scans, correlated strongly with MRI-measured TATM: (R (2) 0·70-0·82). Estimated TATFM correlated well with published prediction equations for total body fat based on underwater weighing (R (2) 0·70-0·80), with mean bias of 2·5-4·9 kg, correctable with log-transformation in most equations. In conclusion, new equations, using simple anthropometric measurements, estimated MRI-measured TATM with correlations and

  8. 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

  9. Characterization and osteogenic potential of equine muscle tissue- and periosteal tissue-derived mesenchymal stem cells in comparison with bone marrow- and adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Radtke, Catherine L; Nino-Fong, Rodolfo; Esparza Gonzalez, Blanca P; Stryhn, Henrik; McDuffee, Laurie A

    2013-05-01

    To characterize equine muscle tissue- and periosteal tissue-derived cells as mesenchymal stem cells (MSCs) and assess their proliferation capacity and osteogenic potential in comparison with bone marrow- and adipose tissue-derived MSCs. Tissues from 10 equine cadavers. Cells were isolated from left semitendinosus muscle tissue, periosteal tissue from the distomedial aspect of the right tibia, bone marrow aspirates from the fourth and fifth sternebrae, and adipose tissue from the left subcutaneous region. Mesenchymal stem cells were characterized on the basis of morphology, adherence to plastic, trilineage differentiation, and detection of stem cell surface markers via immunofluorescence and flow cytometry. Mesenchymal stem cells were tested for osteogenic potential with osteocalcin gene expression via real-time PCR assay. Mesenchymal stem cell cultures were counted at 24, 48, 72, and 96 hours to determine tissue-specific MSC proliferative capacity. Equine muscle tissue- and periosteal tissue-derived cells were characterized as MSCs on the basis of spindle-shaped morphology, adherence to plastic, trilineage differentiation, presence of CD44 and CD90 cell surface markers, and nearly complete absence of CD45 and CD34 cell surface markers. Muscle tissue-, periosteal tissue-, and adipose tissue-derived MSCs proliferated significantly faster than did bone marrow-derived MSCs at 72 and 96 hours. Equine muscle and periosteum are sources of MSCs. Equine muscle- and periosteal-derived MSCs have osteogenic potential comparable to that of equine adipose- and bone marrow-derived MSCs, which could make them useful for tissue engineering applications in equine medicine.

  10. Combined effects of electromagnetic field and low-level laser increase proliferation and alter the morphology of human adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Nurković, Jasmin; Zaletel, Ivan; Nurković, Selmina; Hajrović, Šefćet; Mustafić, Fahrudin; Isma, Jovan; Škevin, Aleksandra Jurišić; Grbović, Vesna; Filipović, Milica Kovačević; Dolićanin, Zana

    2017-01-01

    In recent years, electromagnetic field (EMF) and low-level laser (LLL) have been found to affect various biological processes, the growth and proliferation of cells, and especially that of stem cells. The aim of this study was to investigate the effects of EMF and LLL on proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and thus to examine the impact of these therapeutic physical modalities on stem cell engraftment. hAT-MSCs were isolated from subcutaneous adipose tissue of six persons ranging in age from 21 to 56 years. EMF was applied for a period of 7 days, once a day for 30 min, via a magnetic cushion surface at a frequency of 50 Hz and an intensity of 3 mT. LLL was applied also for 7 days, once a day for 5 min, at radiation energies of 3 J/cm 2 , with a wavelength of 808 nm, power output of 200 mW, and power density of 0.2 W/cm 2 . Nonexposed cells (control) were cultivated under the same culture conditions. Seven days after treatment, the cells were examined for cell viability, proliferation, and morphology. We found that after 7 days, the number of EMF-treated hAT-MSCs was significantly higher than the number of the untreated cells, LLL-treated hAT-MSCs were more numerous than EMF-treated cells, and hAT-MSCs that were treated with the combination of EMF and LLL were the most numerous. EMF and/or LLL treatment did not significantly affect hAT-MSC viability by itself. Changes in cell morphology were also observed, in terms of an increase in cell surface area and fractal dimension in hAT-MSCs treated with EMF and the combination of EMF and LLL. In conclusion, EMF and/or LLL treatment accelerated the proliferation of hAT-MSCs without compromising their viability, and therefore, they may be used in stem cell tissue engineering.

  11. AMP-Activated Kinase (AMPK Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype.

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    Omar Abdul-Rahman

    Full Text Available Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R-5-(4-Carbamoyl-5-aminoimidazol-1-yl-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR, a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained

  12. 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.

  13. In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis.

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    Jane Ru Choi

    Full Text Available Adipose tissue-derived stromal cells (ASCs natively reside in a relatively low-oxygen tension (i.e., hypoxic microenvironment in human body. Low oxygen tension (i.e., in situ normoxia, has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2 or in situ normoxia (2% O2. We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.

  14. Antioxidants inhibit advanced glycosylation end-product-induced apoptosis by downregulation of miR-223 in human adipose tissue-derived stem cells

    Science.gov (United States)

    Wang, Zhe; Li, Hongqiu; Guo, Ran; Wang, Qiushi; Zhang, Dianbao

    2016-01-01

    Advanced glycosylation end products (AGEs) are endogenous inflammatory mediators that induce apoptosis of mesenchymal stem cells. A potential mechanism includes increased generation of reactive oxygen species (ROS). MicroRNA-223 (miR-223) is implicated in the regulation of cell growth and apoptosis in several cell types. Here, we tested the hypothesis that antioxidants N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) inhibit AGE-induced apoptosis via a microRNA-dependent mechanism in human adipose tissue-derived stem cells (ADSCs). Results showed that AGE-HSA enhanced apoptosis and caspase-3 activity in ADSCs. AGE-HSA also increased ROS generation and upregulated the expression of miR-223. Interestingly, reductions in ROS generation and apoptosis, and upregulation of miR-223 were found in ADSCs treated with antioxidants NAC and AAP. Furthermore, miR-223 mimics blocked antioxidant inhibition of AGE-induced apoptosis and ROS generation. Knockdown of miR-223 amplified the protective effects of antioxidants on apoptosis induced by AGE-HSA. miR-223 acted by targeting fibroblast growth factor receptor 2. These results indicate that NAC and AAP suppress AGE-HSA-induced apoptosis of ADSCs, possibly through downregulation of miR-223. PMID:26964642

  15. Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal stem cells derived from menstrual blood, bone marrow and adipose tissue.

    Science.gov (United States)

    Kozhukharova, Irina; Zemelko, Victoria; Kovaleva, Zoya; Alekseenko, Larisa; Lyublinskaya, Olga; Nikolsky, Nikolay

    2018-03-01

    Doxorubicin (Dox) is an effective anticancer drug with known activity against a wide spectrum of malignancies, hematologic malignancies in particular. Despite extensive clinical use, the mechanisms of its side effects and negative action on normal cells remain under study. The aim of this study was to investigate the effect of Dox on cultured human mesenchymal stem cells (MSCs) derived from menstrual blood (eMSCs), bone marrow (BMSCs) and adipose tissue (AMSCs). Dox treatment in high doses decreased the survival of MSCs in a dose-dependent manner. Clinically relevant low doses of Dox induced premature senescence of eMSCs, BMSCs and AMSCs, but did not kill the cells. Dox caused cell cycle arrest and formation of γ-H2AX foci, and increased the number of SA-β-gal-positive cells. BMSCs entered premature senescence earlier than other MSCs. It has been reported that neural-like cells differentiated from MSCs of various origins are more sensitive to Dox than their parent cells. Dox-treated differentiated MSCs exhibited lower viability and earlier generation of γ-H2AX foci. Dox administration inhibited secretory activity in neural-like cells. These findings suggest that a clinically relevant Dox dose damages cultured MSCs, inducing their premature senescence. MSCs are more resistant to this damage than differentiated cells.

  16. Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells

    Science.gov (United States)

    Liao, Naishun; Wu, Ming; Pan, Fan; Lin, Jiumao; Li, Zuanfang; Zhang, Da; Wang, Yingchao; Zheng, Youshi; Peng, Jun; Liu, Xiaolong; Liu, Jingfeng

    2016-01-01

    Tracking and monitoring of cells in vivo after transplantation can provide crucial information for stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be an effective and non-invasive technique for cell tracking in living bodies. However, commercial superparamagnetic iron oxide nanoparticles (SPIONs) applied to label cells suffer from shortages such as potential toxicity, low labeling efficiency, and low contrast enhancing. Herein, the adipose tissue-derived stem cells (ADSCs) were efficiently labeled with SPIONs coated with poly (dopamine) (SPIONs cluster@PDA), without affecting their viability, proliferation, apoptosis, surface marker expression, as well as their self-renew ability and multi-differentiation potential. The labeled cells transplanted into the mice through tail intravenous injection exhibited a negative enhancement of the MRI signal in the damaged liver-induced by carbon tetrachloride, and subsequently these homed ADSCs with SPIONs cluster@PDA labeling exhibited excellent repair effects to the damaged liver. Moreover, the enhanced target-homing to tissue of interest and repair effects of SPIONs cluster@PDA-labeled ADSCs could be achieved by use of external magnetic field in the excisional skin wound mice model. Therefore, we provide a facile, safe, noninvasive and sensitive method for external magnetic field targeted delivery and MRI based tracking of transplanted cells in vivo.

  17. Acute myocardial infarction does not affect functional characteristics of adipose-derived stem cells in rats, but reduces the number of stem cells in adipose tissue.

    Science.gov (United States)

    Naaijkens, B A; Krijnen, P A J; Meinster, E; ter Horst, E N; Vo, K; Musters, R J P; Kamp, O; Niessen, H W M; Juffermans, L J M; van Dijk, A

    2015-12-01

    In most pre-clinical animal studies investigating stem cell therapy in acute myocardial infarction (AMI), the administered stem cells are isolated from healthy donors. In clinical practice, however, patients who suffer from AMI will receive autologous cells, for example using adipose-derived stem cells (ASC). During AMI, inflammation is induced and we hypothesized that this might affect characteristics of ASC. To investigate this, ASC were isolated from rat adipose tissue 1 day (1D group, n = 5) or 7 days (7D group, n = 6) post-AMI, and were compared with ASC from healthy control rats (Control group, n = 6) and sham-operated rats (Sham 1D group, n = 5). We found that significantly fewer ASC were present 1 day post-AMI in the stromal vascular fraction (SVF), determined by a colony-forming-unit assay (p cells in SVF of the 1D group. When cultured, no differences were found in proliferation rate and cell size between the groups in the first three passages. Also, no difference in the differentiation capacity of ASC was found. In conclusion, it was shown that significantly fewer stem cells were present in the SVF 1 day post-AMI; however, the stem cells that were present showed no functional differences.

  18. The combination of miR-122 overexpression and Let-7f silencing induces hepatic differentiation of adipose tissue-derived stem cells.

    Science.gov (United States)

    Davoodian, Nahid; Lotfi, Abbas S; Soleimani, Masoud; Ghaneialvar, Hori

    2017-10-01

    Human adipose tissue-derived stem cells (hADSCs) have been considered as a promising source for cell therapy of liver diseases due to their accessibility, abundance, and expression of hepatocyte markers. Currently, the important role of certain microRNAs (miRNAs) has been reported during hepatic differentiation of stem cells. However, the combination effect of miRNAs on hepatic differentiation of these cells needs to be more investigated. The present study seeks to determine whether the combination of miRNAs can enhance hepatic differentiation of hADSCs in the absence of any other stimulation. First, lentiviral transduction was used to overexpress miR-122 and silence d let-7f in hADSCs for up to 21 days. Then, hepatic functionality was evaluated by analyzing specific hepatocyte genes and biochemical markers at different time points of differentiation induction. Stable miR-122 overexpression and let-7f silencing together in hADSCs resulted in increased expression of hepatocyte markers including ALB, AFP, CK18, CK19, and HNF4a. In addition, urea and albumin production, immunocytochemistry, and glycogen staining confirmed that the treated cells differentiated toward hepatocyte-like cells. Therefore, our findings demonstrate the possibility of using microRNAs to induce hADSCs into functional hepatocyte-like cells. © 2017 International Federation for Cell Biology.

  19. Complete resolution of avascular necrosis of the human femoral head treated with adipose tissue-derived stem cells and platelet-rich plasma.

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Jeon, Jeong Ho; Lee, Sang Hee

    2014-12-01

    We report a case of a 43-year-old man with early stage (stage 1) avascular necrosis (AVN) of the femoral head treated with adipose tissue-derived stem cells (ASCs) and platelet-rich plasma (PRP). ASC-containing stromal vascular fraction was mixed with PRP and hyaluronic acid. This mixture was then injected into the diseased hip under ultrasound guidance. The affected hip was reinjected weekly with additional PRP for 4 weeks. The patient was followed-up with sequential magnetic resonance imaging (MRI) scans at 3, 18, and 21 months after treatment, together with Visual Analogue Scale (VAS) Walking Index, Functional Rating Index, Harris Hip Score, and Range of Motion (ROM) assessments. The patient's severe hip pain was considerably improved at 3 months after treatment, with pain scores, ROM and MRI showing near complete resolution of AVN. Pain scores, ROM and MRI at 18 and 21 months after treatment indicated complete resolution of AVN. This case represents the first evidence of complete resolution of early stage AVN of the hip following treatment with ASCs/PRP. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. Conditioned Media from Adipose-Tissue-Derived Mesenchymal Stem Cells Downregulate Degradative Mediators Induced by Interleukin-1β in Osteoarthritic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Julia Platas

    2013-01-01

    Full Text Available Osteoarthritis (OA is the most frequent joint disorder and an important cause of disability. Recent studies have shown the potential of adipose-tissue-derived mesenchymal stem cells (AD-MSC for cartilage repair. We have investigated whether conditioned medium from AD-MSC (CM may regulate in OA chondrocytes a number of key mediators involved in cartilage degeneration. CM enhanced type II collagen expression in OA chondrocytes while decreasing matrix metalloproteinase (MMP activity in cell supernatants as well as the levels of MMP-3 and MMP-13 proteins and mRNA in OA chondrocytes stimulated with interleukin- (IL- 1β. In addition, CM increased IL-10 levels and counteracted the stimulating effects of IL-1β on the production of tumor necrosis factor-α, IL-6, prostaglandin E2, and NO measured as nitrite and the mRNA expression of these cytokines, CCL-2, CCL-3, CCL-4, CCL-5, CCL-8, CCL-19, CCL-20, CXCL-1, CXCL-2, CXCL-3, CXCL-5, CXCL-8, cyclooxygenase-2, microsomal prostaglandin E synthase-1, and inducible NO synthase. These effects may be dependent on the inhibition of nuclear factor-κB activation by CM. Our data demonstrate the chondroprotective actions of CM and provide support for further studies of this approach in joint disease.

  1. Antagonizing Effects of Aspartic Acid against Ultraviolet A-Induced Downregulation of the Stemness of Human Adipose Tissue-Derived Mesenchymal Stem Cells.

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    Kwangseon Jung

    Full Text Available Ultraviolet A (UVA irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate effects of aspartic acid on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs. Furthermore, we elucidated the UVA-antagonizing mechanisms of aspartic acid. The results of this study showed that aspartic acid attenuated the UVA-induced reduction of the proliferative potential and stemness of hAMSCs, as evidenced by increased proliferative activity in the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and upregulation of stemness-related genes OCT4, NANOG, and SOX2 in response to the aspartic acid treatment. UVA-induced reduction in the mRNA level of hypoxia-inducible factor (HIF-1α was also significantly recovered by aspartic acid. In addition, the antagonizing effects of aspartic acid against the UVA effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show that aspartic acid improves reduced stemness of hAMSCs induced by UVA and its effects are mediated by upregulation of HIF-1α via the inhibition of PGE2-cAMP signaling. In addition, aspartic acid may be used as an antagonizing agent to mitigate the effects of UVA.

  2. The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines.

    Science.gov (United States)

    Visweswaran, Malini; Arfuso, Frank; Dilley, Rodney J; Newsholme, Philip; Dharmarajan, Arun

    2018-02-01

    Tumours exhibit a heterogeneous mix of cell types that reciprocally regulate their growth in the tumour stroma, considerably affecting the progression of the disease. Both adipose-derived mesenchymal stem cells and Wnt signalling pathway are vital in driving breast tumour growth. Hence, we examined the effect of secreted factors released by adipose-derived mesenchymal stem cells, and further explored the anti-tumour property of the Wnt antagonist secreted frizzled-related protein 4 (sFRP4) on MCF-7 and MDA-MB-231 breast tumour cells. We observed that conditioned medium and extracellular matrix derived from adipose-derived mesenchymal stem cells inhibited tumour viability. The inhibitory effect of the conditioned medium was retained within its low molecular weight and non-protein component. The conditioned medium also induced apoptosis accompanied by a decrease in the mitochondrial membrane potential in tumour cells, Furthermore, it downregulated the protein expression of active β-catenin and Cyclin D1, which are major target proteins of the Wnt signalling pathway, and reduced the expression of anti-apoptotic protein Bcl-xL. The combination of conditioned medium and sFRP4 further potentiated the effects, depending on the tumour cell line and experimental assay. We conclude that factors derived from conditioned medium of adipose-derived mesenchymal stem cells and sFRP4 significantly decreased the tumour cell viability and migration rates (MCF-7), accompanied with an enhanced apoptotic activity through inhibition of canonical Wnt signalling. Besides giving an insight to possible paracrine interactions and influence of signalling pathways, reflective of a breast tumour microenvironment, this study emphasises the utilization of cell free-secreted factors and Wnt antagonists to improve conventional anti-cancer strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. 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....

  4. The role of SDF-1-CXCR4/CXCR7 axis in biological behaviors of adipose tissue-derived mesenchymal stem cells in vitro

    International Nuclear Information System (INIS)

    Li, Qiang; Zhang, Aijun; Tao, Changbo; Li, Xueyang; Jin, Peisheng

    2013-01-01

    Highlights: •SDF-1 pretreating increased the levels of CXCR4, CXCR7 in ADSCs. •SDF-1 improved cells paracrine migration and proliferation abilities. •CXCR4 and CXCR7 could function in ADSCs paracrine, migration and proliferation. -- Abstract: Numerous studies have reported that CXCR4 and CXCR7 play an essential, but differential role in stromal cell-derived factor-1 (SDF-1)-inducing cell chemotaxis, viability and paracrine actions of BMSCs. Adipose tissue-derived mesenchymal stem cells (ADSCs) have been suggested to be potential seed cells for clinical application instead of bone marrow derived stroma cell (BMSCs). However, the function of SDF-1/CXCR4 and SDF-1/CXCR7 in ADSCs is not well understood. This study was designed to analyze the effect of SDF-1/CXCR4 and SDF-1/CXCR7 axis on ADSCs biological behaviors in vitro. Using Flow cytometry and Western blot methods, we found for the first time that CXCR4/CXCR7 expression was increased after treatment with SDF-1 in ADSCs. SDF-1 promoted ADSCs paracrine, proliferation and migration abilities. CXCR4 or CXCR7 antibody suppressed ADSCs paracrine action induced by SDF-1. The migration of ADSCs can be abolished by CXCR4 antibody, while the proliferation of ADSCs was only downregulated by CXCR7 antibody. Our study indicated that the angiogenesis of ADSCs is, at least partly, mediated by SDF-1/CXCR4 and SDF-1/CXCR7 axis. However, only binding of SDF-1/CXCR7 was required for proliferation of ADSCs, and CXCR7 was required for migration of ADSCs induced by SDF-1. Our studies provide evidence that the activation of either axis may be helpful to improve the effectiveness of ADSCs-based stem cell therapy

  5. The role of SDF-1-CXCR4/CXCR7 axis in biological behaviors of adipose tissue-derived mesenchymal stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qiang; Zhang, Aijun; Tao, Changbo; Li, Xueyang; Jin, Peisheng, E-mail: jinps2006@163.com

    2013-11-22

    Highlights: •SDF-1 pretreating increased the levels of CXCR4, CXCR7 in ADSCs. •SDF-1 improved cells paracrine migration and proliferation abilities. •CXCR4 and CXCR7 could function in ADSCs paracrine, migration and proliferation. -- Abstract: Numerous studies have reported that CXCR4 and CXCR7 play an essential, but differential role in stromal cell-derived factor-1 (SDF-1)-inducing cell chemotaxis, viability and paracrine actions of BMSCs. Adipose tissue-derived mesenchymal stem cells (ADSCs) have been suggested to be potential seed cells for clinical application instead of bone marrow derived stroma cell (BMSCs). However, the function of SDF-1/CXCR4 and SDF-1/CXCR7 in ADSCs is not well understood. This study was designed to analyze the effect of SDF-1/CXCR4 and SDF-1/CXCR7 axis on ADSCs biological behaviors in vitro. Using Flow cytometry and Western blot methods, we found for the first time that CXCR4/CXCR7 expression was increased after treatment with SDF-1 in ADSCs. SDF-1 promoted ADSCs paracrine, proliferation and migration abilities. CXCR4 or CXCR7 antibody suppressed ADSCs paracrine action induced by SDF-1. The migration of ADSCs can be abolished by CXCR4 antibody, while the proliferation of ADSCs was only downregulated by CXCR7 antibody. Our study indicated that the angiogenesis of ADSCs is, at least partly, mediated by SDF-1/CXCR4 and SDF-1/CXCR7 axis. However, only binding of SDF-1/CXCR7 was required for proliferation of ADSCs, and CXCR7 was required for migration of ADSCs induced by SDF-1. Our studies provide evidence that the activation of either axis may be helpful to improve the effectiveness of ADSCs-based stem cell therapy.

  6. Uremic Toxins Affect the Imbalance of Redox State and Overexpression of Prolyl Hydroxylase 2 in Human Adipose Tissue-Derived Mesenchymal Stem Cells Involved in Wound Healing.

    Science.gov (United States)

    Khanh, Vuong Cat; Ohneda, Kinuko; Kato, Toshiki; Yamashita, Toshiharu; Sato, Fujio; Tachi, Kana; Ohneda, Osamu

    2017-07-01

    Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions. Consistent with the uremic-treated AT-MSCs, there was a definite imbalance of redox state and high expression of ROS in CKD-AT-MSCs isolated from early-stage CKD patients. In addition, a transplantation study clearly revealed that nAT-MSCs promoted the recruitment of inflammatory cells and recovery from ischemia in the mouse flap model, whereas CKD-AT-MSCs had defective functions and the wound healing process was delayed. Of note, the expression of prolyl hydroxylase domain 2 (PHD2) is selectively increased in CKD-AT-MSCs and its inhibition can restore the expression of HIF-1α and the wound healing function of CKD-AT-MSCs. These results indicate that more studies about the functions of MSCs from CKD patients are required before they can be applied in the clinical setting.

  7. Estimation of CT-derived abdominal visceral and subcutaneous adipose tissue depots from anthropometry in Europeans, South Asians and African Caribbeans.

    Directory of Open Access Journals (Sweden)

    Sophie V Eastwood

    Full Text Available South Asians and African Caribbeans experience more cardiometabolic disease than Europeans. Risk factors include visceral (VAT and subcutaneous abdominal (SAT adipose tissue, which vary with ethnicity and are difficult to quantify using anthropometry.We developed and cross-validated ethnicity and gender-specific equations using anthropometrics to predict VAT and SAT.669 Europeans, 514 South Asians and 227 African Caribbeans (70 ± 7 years underwent anthropometric measurement and abdominal CT scanning. South Asian and African Caribbean participants were first-generation migrants living in London. Prediction equations were derived for CT-measured VAT and SAT using stepwise regression, then cross-validated by comparing actual and predicted means.South Asians had more and African Caribbeans less VAT than Europeans. For basic VAT prediction equations (age and waist circumference, model fit was better in men (R(2 range 0.59-0.71 than women (range 0.35-0.59. Expanded equations (+ weight, height, hip and thigh circumference improved fit for South Asian and African Caribbean women (R(2 0.35 to 0.55, and 0.43 to 0.56 respectively. For basic SAT equations, R(2 was 0.69-0.77, and for expanded equations it was 0.72-0.86. Cross-validation showed differences between actual and estimated VAT of <7%, and SAT of <8% in all groups, apart from VAT in South Asian women which disagreed by 16%.We provide ethnicity- and gender-specific VAT and SAT prediction equations, derived from a large tri-ethnic sample. Model fit was reasonable for SAT and VAT in men, while basic VAT models should be used cautiously in South Asian and African Caribbean women. These equations will aid studies of mechanisms of cardiometabolic disease in later life, where imaging data are not available.

  8. The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate.

    Science.gov (United States)

    Grudzenski, Saskia; Baier, Sebastian; Ebert, Anne; Pullens, Pim; Lemke, Andreas; Bieback, Karen; Dijkhuizen, Rick M; Schad, Lothar R; Alonso, Angelika; Hennerici, Michael G; Fatar, Marc

    2017-04-26

    In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 10 6 cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI). Male Wistar rats (n = 43) underwent a middle cerebral artery occlusion (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 × 10 6 , 3 × 10 5 , or 5 × 10 4 ASCs pre-labelled with very small superparamagnetic iron oxide particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo. Lesion volumes were assessed by analysis of T2-weighted images and cell signal tracking showing cell engraftment and active cell migration by an improved T2*-analysis. The ASC-derived signal intensity increased in the affected hemisphere 48 h post MCAo with injected cell number (p cell numbers between both MRI examinations but showed active ASC migration to the site of infarction. Our results confirm that IA injection is an efficient way of targeting damaged brain tissue but its usefulness strongly depends on the right dose of delivered stem cells since this factor has a strong influence on migration rate and infarct volume, with better results for doses below 1 × 10 6 cells. Future challenges will include the determination of therapeutic doses for best cellular engraftment and stroke outcome.

  9. Improved viability and activity of neutrophils differentiated from HL-60 cells by co-culture with adipose tissue-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yoon Shin; Lim, Goh-Woon [Department of Pediatrics, Ewha Womans University, School of Medicine, Ewha Medical Research Center, Seoul (Korea, Republic of); Cho, Kyung-Ah; Woo, So-Youn; Shin, Meeyoung [Department of Microbiology, Ewha Womans University, School of Medicine, Ewha Medical Research Center, Seoul (Korea, Republic of); Yoo, Eun-Sun [Department of Pediatrics, Ewha Womans University, School of Medicine, Ewha Medical Research Center, Seoul (Korea, Republic of); Chan Ra, Jeong [Stem Cell Research Center, RNL BIO, Seoul 153-768 (Korea, Republic of); Ryu, Kyung-Ha, E-mail: ykh@ewha.ac.kr [Department of Pediatrics, Ewha Womans University, School of Medicine, Ewha Medical Research Center, Seoul (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Neutropenia is a principal complication of cancer treatment. Black-Right-Pointing-Pointer Co-culture of neutrophils with AD-MSC retained cell survival and proliferation and inhibited neutrophil apoptosis under serum starved conditions. Black-Right-Pointing-Pointer AD-MSC increased functions of neutrophil. Black-Right-Pointing-Pointer AD-MSC promoted the viability of neutrophils by enhancing respiratory burst through the expression of IFN-{alpha}, G-CSF, and TGF-{beta}. Black-Right-Pointing-Pointer AD-MSC can be used to improve immunity for neutropenia treatment. -- Abstract: Neutropenia is a principal complication of cancer treatment. We investigated the supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on the viability and function of neutrophils. Neutrophils were derived from HL-60 cells by dimethylformamide stimulation and cultured with or without AD-MSCs under serum-starved conditions to evaluate neutrophil survival, proliferation, and function. Serum starvation resulted in the apoptosis of neutrophils and decreased cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell survival and inhibited neutrophil apoptosis under serum-starved conditions. The survival rate of neutrophils was prolonged up to 72 h, and the expression levels of interferon (IFN)-{alpha}, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-{beta} in AD-MSCs were increased after co-culture with neutrophils. AD-MSCs promoted the viability of neutrophils by inhibiting apoptosis as well as enhancing respiratory burst, which could potentially be mediated by the increased expression of IFN-{alpha}, G-CSF, and TGF-{beta}. Thus, we conclude that the use of AD-MSCs may be a promising cell-based therapy for increasing immunity by accelerating neutrophil function.

  10. 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.

  11. miR-21 modulates tumor outgrowth induced by human adipose tissue-derived mesenchymal stem cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Keun Koo; Lee, Ae Lim; Kim, Jee Young [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Sun Young [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Bae, Yong Chan [Department of Plastic Surgery, School of Medicine, Pusan National University, Pusan 602-739 (Korea, Republic of); Jung, Jin Sup, E-mail: jsjung@pusan.ac.kr [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Institute, Pusan National University, Pusan 602-739 (Korea, Republic of)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer miR-21 modulates hADSC-induced increase of tumor growth. Black-Right-Pointing-Pointer The action is mostly mediated by the modulation of TGF-{beta} signaling. Black-Right-Pointing-Pointer Inhibition of miR-21 enhances the blood flow recovery in hindlimb ischemia. -- Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs on tumor growth in vivo, and the long-term safety of the clinical applications of MSCs, can be more thoroughly understood. In this study, we determined whether microRNAs can modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR-21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor growth, and inhibition of miR-21 increased it. Downregulation of transforming growth factor beta receptor II (TGFBR2), but not of signal transducer and activator of transcription 3, in hADSCs showed effects similar to those of miR-21 overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased tumor vascularity. Inhibition of miR-21 and the addition of TGF-{beta} increased the levels of vascular endothelial growth factor and interleukin-6 in hADSCs. Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow recovery in a hind limb ischemia model of nude mice, compared with transplantation of control oligo-transfected cells. These findings indicate that MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    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

  14. Adhesion profile and differentiation capacity of human adipose tissue derived mesenchymal stem cells grown on metal ion (Zn, Ag and Cu) doped hydroxyapatite nano-coated surfaces.

    Science.gov (United States)

    Bostancioglu, R Beklem; Gurbuz, Mevlut; Akyurekli, Ayse Gul; Dogan, Aydin; Koparal, A Savas; Koparal, A Tansu

    2017-07-01

    Accelerated Mesenchymal Stem Cells (MSCs) condensation and robust MSC-matrix and MSC-MSC interactions on nano-surfaces may provide critical factors contributing to such events, likely through the orchestrated signal cascades and cellular events modulated by the extracellular matrix. In this study, human adipose tissue derived mesenchymal stem cells (hMSC)', were grown on metal ion (Zn, Ag and Cu) doped hydroxyapatite (HAP) nano-coated surfaces. These metal ions are known to have different chemical and surface properties; therefore we investigated their respective contributions to cell viability, cellular behavior, osteogenic differentiation capacity and substrate-cell interaction. Nano-powders were produced using a wet chemical process. Air spray deposition was used to accumulate the metal ion doped HAP films on a glass substrate. Cell viability was determined by MTT, LDH and DNA quantitation methods Osteogenic differentiation capacity of hMSCs was analyzed with Alizarin Red Staining and Alkaline Phosphatase Specific Activity. Adhesion of the hMSCs and the effect of cell adhesion on biomaterial biocompatibility were explored through cell adhesion assay, immunofluorescence staining for vinculin and f-actin cytoskeleton components, SEM and microarray including 84 known extracellular matrix proteins and cell adhesion pathway genes, since, adhesion is the first step for good biocompability. The results demonstrate that the viability and osteogenic differentiation of the hMSCs (in growth media without osteogenic stimulation) and cell adhesion capability are higher on nanocoated surfaces that include Zn, Ag and/or Cu metal ions than commercial HAP. These results reveal that Zn, Ag and Cu metal ions contribute to the biocompatibility of exogenous material. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept.

    Science.gov (United States)

    Angelone, Mario; Conti, Virna; Biacca, Cristiano; Battaglia, Beatrice; Pecorari, Laura; Piana, Francesco; Gnudi, Giacomo; Leonardi, Fabio; Ramoni, Roberto; Basini, Giuseppina; Dotti, Silvia; Renzi, Sabrina; Ferrari, Maura; Grolli, Stefano

    2017-10-11

    Laminitis, a highly debilitating disease of the foot in ungulates, is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial disease that involves perturbation of the vascular, hematological, and inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the disease resembles what is observed in metabolic syndromes and sepsis-induced organ failure in humans and animals. We hypothesized that local administration of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) might contribute to establishing an anti-inflammatory and pro-angiogenic environment, and could stimulate the injured tissue in order to restore its functional integrity. According to this assumption, an experimental protocol based on the local intravenous administration of adipose tissue-derived MSCs (aMSCs) in combination with PRP was developed for the treatment of horses affected by chronic laminitis. Nine horses with severely compromised venograms (showing grade III and IV laminitis) that had been unsuccessfully treated with conventional therapies were enrolled. aMSCs and PRP (15 × 10⁶ cells resuspended in 15 mL of PRP) were injected into the lateral or medial digital vein three times, at one-month intervals. The first administration was performed with allogeneic aMSCs, while for the following administrations, autologous aMSCs were used. There was no adverse short-term reaction to the intravenous injection of aMSCs. In the long term, venograms outlined, in all subjects, a progressive amelioration of the vascularization of the foot. An improvement in the structure and function of the hoof was also observed. No adverse events were reported during the follow-up, and the horses returned to a comfortable quality of life. Although the number of animals enrolled in the study is limited, both clinical observations and venography demonstrated an enhancement in the condition of all

  16. Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem cells, and platelet rich plasma, for treating surgically induced lesions of the equine superficial digital flexor tendon.

    Science.gov (United States)

    Romero, A; Barrachina, L; Ranera, B; Remacha, A R; Moreno, B; de Blas, I; Sanz, A; Vázquez, F J; Vitoria, A; Junquera, C; Zaragoza, P; Rodellar, C

    2017-06-01

    Several therapies have been investigated for equine tendinopathies, but satisfactory long term results have not been achieved consistently and a better understanding of the healing mechanism elicited by regenerative therapies is needed. The aim of this study was to assess the separate effects of autologous bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs), and platelet rich plasma (PRP), for treating lesions induced in the superficial digital flexor tendon (SDFT) of horses. Lesions were created surgically in both SDFTs of the forelimbs of 12 horses and were treated with BM-MSCs (six tendons), AT-MSCs (six tendons) or PRP (six tendons). The remaining six tendons received lactated Ringer's solution as control. Serial ultrasound assessment was performed prior to treatment and at 2, 6, 10, 20 and 45 weeks post-treatment. At 45 weeks, histopathology and gene expression analyses were performed. At week 6, the ultrasound echogenicity score in tendons treated with BM-MSCs suggested earlier improvement, whilst all treatment groups reached the same level at week 10, which was superior to the control group. Collagen orientation scores on histological examination suggested a better outcome in treated tendons. Gene expression was indicative of better tissue regeneration after all treatments, especially for BM-MSCs, as suggested by upregulation of collagen type I, decorin, tenascin and matrix metalloproteinase III mRNA. Considering all findings, a clear beneficial effect was elicited by all treatments compared with the control group. Although differences between treatments were relatively small, BM-MSCs resulted in a better outcome than PRP and AT-MSCs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

    Science.gov (United States)

    Mello, Debora B; Ramos, Isalira P; Mesquita, Fernanda C P; Brasil, Guilherme V; Rocha, Nazareth N; Takiya, Christina M; Lima, Ana Paula C A; Campos de Carvalho, Antonio C; Goldenberg, Regina S; Carvalho, Adriana B

    2015-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC) can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy. ASC were injected intraperitoneally at 3 days post-infection (dpi). Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV) dilation was prevented in ASC-treated mice. In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

  18. Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

    Directory of Open Access Journals (Sweden)

    Debora B Mello

    Full Text Available Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi, is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy.ASC were injected intraperitoneally at 3 days post-infection (dpi. Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV dilation was prevented in ASC-treated mice.In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

  19. Porcine adipose tissue-derived mesenchymal stem cells retain their proliferative characteristics, senescence, karyotype and plasticity after long-term cryopreservation.

    Directory of Open Access Journals (Sweden)

    Rafael Dariolli

    Full Text Available We and others have provided evidence that adipose tissue-derived mesenchymal stem cells (ASCs can mitigate rat cardiac functional deterioration after myocardial ischemia, even though the mechanism of action or the relevance of these findings to human conditions remains elusive. In this regard, the porcine model is a key translational step, because it displays heart anatomic-physiological features that are similar to those found in the human heart. Towards this end, we wanted to establish the cultural characteristics of porcine ASCs (pASCs with or without long-term cryostorage, considering that allogeneic transplantation may also be a future option. Compared to fresh pASCs, thawed cells displayed 90-95% viability and no changes in morphological characteristics or in the expression of surface markers (being pASCs characterized by positive markers CD29(+; CD90(+; CD44(+; CD140b(+; CD105(+; and negative markers CD31(-; CD34(-; CD45(- and SLA-DR(-; n = 3. Mean population doubling time was also comparable (64.26±15.11 hours to thawed cells vs. 62.74±18.07 hours to fresh cells and cumulative population doubling increased constantly until Passage 10 (P10 in the entire cell population, with a small and gradual increase in senescence (P5, 3.25%±0.26 vs. 3.47%±0.32 and P10, 9.6%±0.29 vs. 10.67%±1.25, thawed vs. fresh; SA-β-Gal staining. Chromosomal aberrations were not observed. In addition, under both conditions pASCs responded to adipogenic and osteogenic chemical cues in vitro. In conclusion, we have demonstrated the growth characteristics, senescence, and the capacity of pASCs to respond to chemical cues in vitro and have provided evidence that these properties are not influenced by cryostorage in 10% DMSO solution.

  20. Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.

    Science.gov (United States)

    Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa

    2017-10-01

    Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

  1. Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes.

    Science.gov (United States)

    Pérez-Merino, E M; Usón-Casaús, J M; Zaragoza-Bayle, C; Duque-Carrasco, J; Mariñas-Pardo, L; Hermida-Prieto, M; Barrera-Chacón, R; Gualtieri, M

    2015-12-01

    Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn's disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

    Directory of Open Access Journals (Sweden)

    Moriyama Mariko

    2012-08-01

    Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

  3. Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Young Woo [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Biomedical Research Institute, Lifeliver Co., Ltd., Suwon (Korea, Republic of); Lee, Jong Eun; Yang, Mal Sook; Jang, In Keun; Kim, Hyo Eun; Lee, Doo Hoon; Kim, Young Jin [Biomedical Research Institute, Lifeliver Co., Ltd., Suwon (Korea, Republic of); Park, Won Jin [Dr. Park' s Aesthetic Clinic, Seoul (Korea, Republic of); Kong, Jee Hyun; Shim, Kwang Yong [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Lee, Jong In, E-mail: oncochem@yonsei.ac.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kim, Hyun Soo, E-mail: khsmd@unitel.co.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

    2011-04-29

    Highlights: {yields} hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. {yields} Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. {yields} hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.

  4. Dual effects of human adipose tissue-derived mesenchymal stem cells in human lung adenocarcinoma A549 xenografts and colorectal adenocarcinoma HT-29 xenografts in mice.

    Science.gov (United States)

    Rhyu, Jung Joo; Yun, Jun-Won; Kwon, Euna; Che, Jeong-Hwan; Kang, Byeong-Cheol

    2015-10-01

    Human adipose tissue-derived mesenchymal stem cells (hATMSCs) have great potential as a therapy for various diseases. However, emerging evidence shows that there are conflicting results concerning effects of hATMSCs on tumor progression. Our objective was to determine whether and how hATMSCs modulate tumor growth. After cancer cell lines were subcutaneously inoculated into BALB/c-nude and hairless severe combined immunodeficient mice, hATMSCs were intratumorally injected into the mice. The growth of the A549 tumors was inhibited by hATMSCs, yet that of the HT-29 tumors was significantly promoted by hATMSCs in the in vivo xenograft models. In vitro study using a co-culture system of cancer cells and hATMSCs was consistent with the in vivo experiments. To reveal the molecular events induced by hATMSCs in the xenograft models, global gene expression profiles of the A549 and HT-29 tumors in the absence or presence of hATMSCs were determined. Significant numbers of genes involved in biological processes were altered in the hATMSC-treated A549 tumors, whereas no biological process was regulated by treatment with hATMSCs in the HT-29 tumors, reflecting the different effects of hATMSCs in the different types of cancer. Notably, histone cluster 1, H2aj and neuropeptide Y receptor Y4 were found to be expressed in direct or inverse proportion to tumor size in both xenograft models. In addition, nuclear factor κB (NF-κB) p65 was differentially phosphorylated by the hATMSCs dependent on the source of the cancer cells. In conclusion, the identified gene profiling and NF-κB signaling provide molecular evidence to explain the conflicting findings in tumor‑MSC studies, although further study is needed to confirm these findings using various types of cancer.

  5. Human adipose-tissue derived stromal cells in combination with hypoxia effectively support ex vivo expansion of cord blood haematopoietic progenitors.

    Directory of Open Access Journals (Sweden)

    Elena R Andreeva

    Full Text Available The optimisation of haematopoietic stem and progenitor cell expansion is on demand in modern cell therapy. In this work, haematopoietic stem/progenitor cells (HSPCs have been selected from unmanipulated cord blood mononuclear cells (cbMNCs due to adhesion to human adipose-tissue derived stromal cells (ASCs under standard (20% and tissue-related (5% oxygen. ASCs efficiently maintained viability and supported further HSPC expansion at 20% and 5% O2. During co-culture with ASCs, a new floating population of differently committed HSPCs (HSPCs-1 grew. This suspension was enriched with СD34+ cells up to 6 (20% O2 and 8 (5% O2 times. Functional analysis of HSPCs-1 revealed cobble-stone area forming cells (CAFCs and lineage-restricted colony-forming cells (CFCs. The number of CFCs was 1.6 times higher at tissue-related O2, than in standard cultivation (20% O2. This increase was related to a rise in the number of multipotent precursors - BFU-E, CFU-GEMM and CFU-GM. These changes were at least partly ensured by the increased concentration of MCP-1 and IL-8 at 5% O2. In summary, our data demonstrated that human ASCs enables the selection of functionally active HSPCs from unfractionated cbMNCs, the further expansion of which without exogenous cytokines provides enrichment with CD34+ cells. ASCs efficiently support the viability and proliferation of cord blood haematopoietic progenitors of different commitment at standard and tissue-related O2 levels at the expense of direct and paracrine cell-to-cell interactions.

  6. Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.

    Science.gov (United States)

    Lee, Chunwoo; Jang, Myoung Jin; Kim, Bo Hyun; Park, Jin Young; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Kim, Choung-Soo

    2017-06-01

    Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

  7. 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.

    Science.gov (United States)

    Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Wen; Zhang, Yu; Wang, Yiwei; Liu, Tianqing

    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 7days in culture medium and encapsulated cell in C/GP/Co hydrogel demonstrated a characteristic morphology with high viability over 5days. 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 4weeks 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. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  8. White adipose tissue: Getting nervous

    NARCIS (Netherlands)

    Fliers, E.; Kreier, F.; Voshol, P. J.; Havekes, L. M.; Sauerwein, H. P.; Kalsbeek, A.; Buijs, R. M.; Romijn, J. A.

    2003-01-01

    Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative

  9. Intracoronary Administration of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction.

    Science.gov (United States)

    Bobi, Joaquim; Solanes, Núria; Fernández-Jiménez, Rodrigo; Galán-Arriola, Carlos; Dantas, Ana Paula; Fernández-Friera, Leticia; Gálvez-Montón, Carolina; Rigol-Monzó, Elisabet; Agüero, Jaume; Ramírez, José; Roqué, Mercè; Bayés-Genís, Antoni; Sánchez-González, Javier; García-Álvarez, Ana; Sabaté, Manel; Roura, Santiago; Ibáñez, Borja; Rigol, Montserrat

    2017-05-03

    Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; P =0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P =0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P =0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P =0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118±18 versus 92.4±24.3 vessels/mm 2 in vehicle; P =0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative

  10. Comparison of immunological properties of bone marrow stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro

    DEFF Research Database (Denmark)

    Niemeyer, Philipp; Kornacker, Martin; Mehlhorn, Alexander

    2007-01-01

    T cells in vitro. Therefore, BMSCs are said to be available for allogenic cell therapy. Although the immunological characteristics of BMSCs have been the subject of various investigations, those of stem cells isolated from adipose tissue (ASCs) have not been adequately described. In addition......Mesenchymal stem cells (MSCs) can be isolated from various tissues and represent an attractive cell population for tissue-engineering purposes. MSCs from bone marrow (bone marrow stromal cells [BMSCs]) are negative for immunologically relevant surface markers and inhibit proliferation of allogenic...... were sought. The pattern of surface antigen expression of BMSCs is the same as that of ASCs. Analogous to BMSCs, undifferentiated cells isolated from adipose tissue lack expression of MHC-II; this is not lost in the course of the osteogenic differentiation process. In co-culture with allogenic PBMCs...

  11. Adipose tissue-derived stem cells in a fibrin implant enhance neovascularization in a peritoneal grafting site: a potential way to improve ovarian tissue transplantation.

    Science.gov (United States)

    Manavella, D D; Cacciottola, L; Desmet, C M; Jordan, B F; Donnez, J; Amorim, C A; Dolmans, M M

    2018-02-01

    Do two different concentrations of human adipose tissue-derived stem cells (ASCs) embedded inside a fibrin scaffold have the potential to differentiate into vessels and aid vascularization in a peritoneal grafting site intended for ovarian tissue transplantation? Human ASCs in low and high concentrations differentiated into vessels when transplanted to mouse peritoneum inside a fibrin matrix, but only high ASC concentrations significantly increased human vessel area 14 days after transplantation. ASCs have multilineage differentiation potential, including proangiogenic properties and have been used in tissue engineering to enhance vascularization in transplanted tissues. Fibrin has been studied and used as an ASC-compatible biomaterial. In vivo experimental model using 22 severe combined immunodeficient mice. In total, 16 mice (eight per group) were intraperitoneally grafted with a fibrin scaffold loaded with two different human ASC concentrations (either 150 000 [L-ASC] or 1 500 000 [H-ASC] cells) and lithium phthalocyanine (LiPc) crystals as oxygen-sensitive probes. Six mice were grafted with an empty fibrin (EF) implant containing only LiPc and served as controls. Levels of partial pressure of oxygen (pO2) in implants were monitored in vivo by electron paramagnetic resonance oximetry (EPR). ASC identification, proliferation, and host and human vascularization were analyzed by immunohistochemistry (IHC). All analyses were performed on post-grafting Days 3, 7 and 14. Prospective experimental study conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to perform pO2 measurements (EPR oximetry), as well as histological (hematoxylin-eosin staining) and IHC (anti-human vimentin, anti-human Ki67, anti-mouse and human double CD34) analyses. A significant increase in pO2 in implants was observed in all groups between Days 3 and 7 (P Scientifique de Belgique (FNRS-PDR Convention T.0077.14, Télévie Grant no. 7.6515.16F

  12. The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept

    Directory of Open Access Journals (Sweden)

    Mario Angelone

    2017-10-01

    Full Text Available Laminitis, a highly debilitating disease of the foot in ungulates, is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial disease that involves perturbation of the vascular, hematological, and inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the disease resembles what is observed in metabolic syndromes and sepsis-induced organ failure in humans and animals. We hypothesized that local administration of mesenchymal stem cells (MSCs and platelet-rich plasma (PRP might contribute to establishing an anti-inflammatory and pro-angiogenic environment, and could stimulate the injured tissue in order to restore its functional integrity. According to this assumption, an experimental protocol based on the local intravenous administration of adipose tissue-derived MSCs (aMSCs in combination with PRP was developed for the treatment of horses affected by chronic laminitis. Nine horses with severely compromised venograms (showing grade III and IV laminitis that had been unsuccessfully treated with conventional therapies were enrolled. aMSCs and PRP (15 × 106 cells resuspended in 15 mL of PRP were injected into the lateral or medial digital vein three times, at one-month intervals. The first administration was performed with allogeneic aMSCs, while for the following administrations, autologous aMSCs were used. There was no adverse short-term reaction to the intravenous injection of aMSCs. In the long term, venograms outlined, in all subjects, a progressive amelioration of the vascularization of the foot. An improvement in the structure and function of the hoof was also observed. No adverse events were reported during the follow-up, and the horses returned to a comfortable quality of life. Although the number of animals enrolled in the study is limited, both clinical observations and venography demonstrated an enhancement in the

  13. Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation

    Energy Technology Data Exchange (ETDEWEB)

    Tatrai, Peter, E-mail: peter.tatrai@biomembrane.hu [Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Karolina ut 29, H-1113 Budapest (Hungary); Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Szepesi, Aron, E-mail: aron.szepesi@biomembrane.hu [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Matula, Zsolt, E-mail: matula.zsolt@gmail.com [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Szigeti, Anna, E-mail: anna.szigeti@biomembrane.hu [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Buchan, Gyoengyi, E-mail: buchan@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Madi, Andras, E-mail: madi@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Stem Cell, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Uher, Ferenc, E-mail: uher@biomembrane.hu [Stem Cell Laboratory, Hungarian National Blood Transfusion Service, Dioszegi ut 64, H-1113 Budapest (Hungary); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer We immortalized human adipose stromal cells (ASCs) with hTERT, Bmi-1, and SV40T. Black-Right-Pointing-Pointer hTERT-only ASCs are prone to transformation, while Bmi-only ASCs become senescent. Black-Right-Pointing-Pointer SV40T introduced along with hTERT abrogates proliferation control and multipotency. Black-Right-Pointing-Pointer hTERT combined with Bmi-1 yields stable phenotype up to 140 population doublings. -- Abstract: Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASC{sup hTERT}, ASC{sup Bmi-1}, ASC{sup Bmi-1+hTERT} and ASC{sup SV40T+hTERT} were tested for transgene expression, telomerase activity, surface immunomarkers, proliferation, osteogenic and adipogenic differentiation, karyotype, tumorigenicity, and cellular senescence. All cell lines have maintained expression of characteristic surface immunomarkers, and none was tumorigenic. However, ASC{sup Bmi-1} had limited replicative potential, while the rapidly proliferating ASC{sup SV40T+hTERT} acquired chromosomal aberrations, departed from MSC phenotype, and lost differentiation capacity. ASC{sup hTERT} and ASC{sup hTERT+Bmi-1}, on the other hand, preserved all essential MSC features and did not senesce after 100 population doublings. Notably, a subpopulation of ASC{sup hTERT} also acquired aberrant karyotype and showed signs of transformation after long-term culture

  14. miR-34a inhibits differentiation of human adipose tissue-derived stem cells by regulating cell cycle and senescence induction.

    Science.gov (United States)

    Park, Ho; Park, Hyeon; Pak, Ha-Jin; Yang, Dong-Yun; Kim, Yun-Hong; Choi, Won-Jun; Park, Se-Jin; Cho, Jung-Ah; Lee, Kyo-Won

    2015-01-01

    MicroRNAs (miRNAs) are critical in the maintenance, differentiation, and lineage commitment of stem cells. Stem cells have the unique property to differentiate into tissue-specific cell types (lineage commitment) during cell division (self-renewal). In this study, we investigated whether miR-34a, a cell cycle-regulating microRNA, could control the stem cell properties of adipose tissue-derived stem cells (ADSCs). First, we found that the expression level of miR-34a was increased as the cell passage number was increased. This finding, however, was inversely correlated with our finding that the overexpression of miR-34a induced the decrease of cell proliferation. In addition, miR-34a overexpression decreased the expression of various cell cycle regulators such as CDKs (-2, -4, -6) and cyclins (-E, -D), but not p21 and p53. The cell cycle analysis showed accumulation of dividing cells at S phase by miR-34a, which was reversible by co-treatment with anti-miR-34a. The potential of adipogenesis and osteogenesis of ADSCs was also decreased by miR-34a overexpression, which was recovered by co-treatment with anti-miR-34a. The surface expression of stem cell markers including CD44 was also down-regulated by miR-34a overexpression as similar to that elicited by cell cycle inhibitors. miR-34a also caused a significant decrease in mRNA expression of stem cell transcription factors as well as STAT-3 expression and phosphorylation. Cytokine profiling revealed that miR-34a significantly modulated IL-6 and -8 production, which was strongly related to cellular senescence. These data suggest the importance of miR-34a for the fate of ADSCs toward senescence rather than differentiation. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  15. The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction.

    Science.gov (United States)

    Koellensperger, Eva; Bonnert, Lilly-Claire; Zoernig, Inka; Marmé, Frederik; Sandmann, Stefanie; Germann, Günter; Gramley, Felix; Leimer, Uwe

    2017-05-25

    In this study we evaluated the interactions of human adipose tissue-derived stem cells (ADSCs) and different human breast cancer cell lines (BRCAs) with regard to the safety of cell-assisted lipotransfers for breast reconstruction and a thereby unintended co-localization of ADSCs and BRCAs. ADSCs were co-cultured with five different human BRCAs (MCF-7, MDA-MB-231, SK-BR-3, ZR-75-30, and EVSA-T) and primary BRCAs from one patient in a transwell system, and cell-cell-interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real-time polymerase chain reaction (PCR) of more than 300 tumor-associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs). Results of co-culture were compared to those of the respective monoculture. Quantitative real-time PCR revealed remarkable changes in the expression of multiple tumor-associated genes in co-culture compared to monocultures of both ADSCs and BRCAs. Concomitantly, the concentration of several tumor-associated proteins, such as cytokines and MMPs, were strongly increased in co-culture. Furthermore, exclusively in co-culture with ADSCs, the different BRCAs were exposed to several important tumor-modulating proteins, such as CCL2, HGF, or interleukins. Co-culture did not significantly affect cellular proliferation of either ADSCs or BRCAs (p > 0.05). The migration of MCF-7 and MDA-MB-231 BRCAs was significantly increased in co-culture with ADSCs by a mean of 11% and 23%, respectively (p = 0.04 and 0.012), as well as that of ADSCs in co-culture with MDA-MB-231, ZR-75-30, and EVSA-T (+11-15%, p = 0.035-0.045). Co-culture with MDA-MB-231, SK-BR-3, and EVSA-T BRCAs significantly increased the invasive behavior of ADSCs by a mean of 24-41% (p = 0.014-0.039). There were no significant differences in the in vitro invasive properties of BRCAs in co-culture compared to monoculture. An in vitro angiogenesis

  16. Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel Therapy for Insulin-Dependent Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    A. V. Vanikar

    2010-01-01

    Full Text Available Aims. Insulin dependent diabetes mellitus (IDDM is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT, 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC and cultured bone marrow (CBM as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4 patients with 1–24-year disease duration, in age group: 13–43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac: 8.47%, and c-peptide levels: 0.1 ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1×103/μL, CD45−/90+/73+:40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1×103/μL, CD45−/34+:0.62%, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques.

  17. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Maroni, Paola [Istituto Ortopedico Galeazzi, Milano (Italy); Brini, Anna Teresa [Istituto Ortopedico Galeazzi, Milano (Italy); Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano (Italy); Arrigoni, Elena [Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano (Italy); Girolamo, Laura de [Istituto Ortopedico Galeazzi, Milano (Italy); Niada, Stefania [Istituto Ortopedico Galeazzi, Milano (Italy); Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano (Italy); Matteucci, Emanuela; Bendinelli, Paola [Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Universita degli Studi di Milano, Milano (Italy); Desiderio, Maria Alfonsina, E-mail: a.desiderio@unimi.it [Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Universita degli Studi di Milano, Milano (Italy)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Acetylation affected hASCs osteodifferentiation through Runx2-PPAR{gamma}. Black-Right-Pointing-Pointer HDACs knocking-down favoured the commitment effect of osteogenic medium. Black-Right-Pointing-Pointer HDACs silencing early activated Runx2 and ALP. Black-Right-Pointing-Pointer PPAR{gamma} reduction and calcium/collagen deposition occurred later. Black-Right-Pointing-Pointer Runx2/PPAR{gamma} target genes were modulated in line with HDACs role in osteo-commitment. -- Abstract: The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) {gamma}. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPAR{gamma} and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPAR{gamma}/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPAR{gamma} target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal

  18. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    OpenAIRE

    M?ller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. ...

  19. Pharmacological and non-pharmacological interventions to influence adipose tissue function

    OpenAIRE

    Westerink, Jan; Visseren, Frank LJ

    2011-01-01

    Abstract Obesity is associated with metabolic derangements such as insulin resistance, inflammation and hypercoagulobility which can all be understood as consequences of adipose tissue dysfunction. The potential role for adipose tissue derived cytokines and adipokines in the development of vascular disease and diabetes may produce a clinical need to influence adipose tissue function. Various pharmacological and non-pharmacological interventions affect plasma cytokine and adipokine levels. The...

  20. Adipose Tissue Immunity and Cancer

    Directory of Open Access Journals (Sweden)

    Victoria eCatalan

    2013-10-01

    Full Text Available Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete proinflammatory adipokines and cytokines providing a microenvironment favourable for tumour growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching towards M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumour growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumour cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumour microenvironment with more sophisticated and selective anti-tumoural drugs.

  1. 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.

  2. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain......-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P

  3. Control of adipose tissue lipolysis in ectotherm vertebrates.

    Science.gov (United States)

    Migliorini, R H; Lima-Verde, J S; Machado, C R; Cardona, G M; Garofalo, M A; Kettelhut, I C

    1992-10-01

    Lipolytic activity of fish (Hoplias malabaricus), toad (Bufo paracnemis), and snake (Philodryas patagoniensis) adipose tissue was investigated in vivo and in vitro. Catecholamines or glucagon did not affect the release of free fatty acids (FFA) by incubated fish and toad adipose tissue. Catecholamines also failed to activate snake adipose tissue lipolysis, which even decreased in the presence of epinephrine. However, glucagon stimulated both the lipolytic activity of reptilian tissue in vitro and the mobilization of FFA to plasma when administered to snakes in vivo. The release of FFA from incubated fish, amphibian, and reptilian adipose tissue increased markedly in the presence of cAMP or xanthine derivatives, inhibitors of phosphodiesterase. Forskolin or fluoride, activators of specific components of the adenylate cyclase system, strongly stimulated toad adipose tissue lipolysis. The data suggest that adipocyte triacylglycerol lipase of ectotherm vertebrates is activated by a cAMP-mediated phosphorylation and that the organization of the membrane-bound adenylate cyclase system is similar to that of mammals.

  4. Adipose tissue remodeling in lipedema: adipocyte death and concurrent regeneration.

    Science.gov (United States)

    Suga, Hirotaka; Araki, Jun; Aoi, Noriyuki; Kato, Harunosuke; Higashino, Takuya; Yoshimura, Kotaro

    2009-12-01

    Lipedema is a disease with unknown etiology presenting as bilateral and symmetric enlargement of the lower extremities due to subcutaneous deposition of the adipose tissue. Here we describe the histopathological features of the lipedema tissue and nonaffected adipose tissue obtained from a typical patient with severe lipedema. Immunohistochemical analyses indicated degenerative and regenerative changes of the lipedema tissue, characterized by crown-like structures (necrotizing adipocytes surrounded by infiltrating CD68+ macrophages; a feature commonly seen in obese adipose tissue) and proliferation of adipose-derived stem/progenitor/stromal cells (Ki67+CD34+ cells), respectively. These findings suggested increased adipogenesis in the lipedema tissue, which may further lead to hypoxia similar to that seen in obesity, resulting in adipocyte necrosis and macrophage recruitment. The confinement to the lower extremities and the difference from systemic obesity warrants further elucidation in future studies.

  5. Adipose tissue oxygenation: Effects on metabolic function

    OpenAIRE

    Hodson, Leanne

    2013-01-01

    With the increasing prevalence of obesity there is a concomitant increase in white adipose tissue dysfunction, with the tissue moving toward a proinflammatory phenotype. Adipose tissue hypoxia has been proposed as a key underlying mechanism triggering tissue dysfunction but data from human, in vivo studies, to support this hypothesis is limited. Human adipose tissue oxygenation has been investigated by direct assessment of tissue oxygen tension (pO2) or by expression of hypoxia-sensitive gene...

  6. Reduced UCP-1 content in in vitro differentiated beige/brite adipocytes derived from preadipocytes of human subcutaneous white adipose tissues in obesity.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available Brown adipose tissue (BAT is a potential therapeutic target to reverse obesity. The purpose of this study was to determine whether primary precursor cells isolated from human adult subcutaneous white adipose tissue (WAT can be induced to differentiate in-vitro into adipocytes that express key markers of brown or beige adipose, and whether the expression level of such markers differs between lean and obese young adult males.Adipogenic precursor cells were isolated from lean and obese individuals from subcutaneous abdominal WAT biopsies. Cells were grown to confluence, differentiated for 2.5 weeks then harvested for measurement of gene expression and UCP1 protein.There was no difference between groups with respect to differentiation into adipocytes, as indicated by oil red-O staining, rates of lipolysis, and expression of adipogenic genes (FABP4, PPARG. WAT genes (HOXC9, RB1 were expressed equally in the two groups. Post differentiation, the beige adipose specific genes CITED1 and CD137 were significantly increased in both groups, but classic BAT markers ZIC1 and LHX8 decreased significantly. Cell lines from both groups also equally increased post-differentiation expression of the thermogenic-responsive gene PPARGC1A (PGC-1α. UCP1 gene expression was undetectable prior to differentiation, however after differentiation both gene expression and protein content were increased in both groups and were significantly greater in cultures from lean compared with obese individuals (p<0.05.Human subcutaneous WAT cells can be induced to attain BAT characteristics, but this capacity is reduced in WAT cells from obese individuals.

  7. Farnesol Has an Anti-obesity Effect in High-Fat Diet-Induced Obese Mice and Induces the Development of Beige Adipocytes in Human Adipose Tissue Derived-Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Hye-Lin Kim

    2017-09-01

    Full Text Available Brown adipocytes dissipate energy as heat and hence have an important therapeutic capacity for obesity. Development of brown-like adipocytes (also called beige is also another attractive target for obesity treatment. Here, we investigated the effect of farnesol, an isoprenoid, on adipogenesis in adipocytes and on the browning of white adipose tissue (WAT as well as on the weight gain of high-fat diet (HFD-induced obese mice. Farnesol inhibited adipogenesis and the related key regulators including peroxisome proliferator-activated receptor γ (PPARγ and CCAAT/enhancer binding protein α through the up-regulation of AMP-activated protein kinase in 3T3-L1 murine adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs. Farnesol markedly increased the expression of uncoupling protein 1 and PPARγ coactivator 1 α in differentiated hAMSCs. In addition, farnesol limited the weight gain in HFD obese mice and induced the development of beige adipocytes in both inguinal and epididymal WAT. These results suggest that farnesol could be a potential therapeutic agent for obesity treatment.

  8. MicroRNA expression profiling in neurogenesis of adipose tissue ...

    Indian Academy of Sciences (India)

    [Cho J. A., Park H., Lim E. H. and Lee K. W. 2011 MicroRNA expression profiling in neurogenesis of adipose tissue-derived stem cells. J. Genet. 90, 81–93] ... capability, however there are considerable challenges to the use of these cells for ... tissues including brain, blood, muscle, skin, bone marrow, umbilical cord blood ...

  9. 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 ...

  10. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-12-01

    Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  11. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: A case report

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-08-01

    Full Text Available Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31-year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage. We generated adipose tissue derived neuronal differentiated mesenchymal stem cells (N-AD-MSC and bone marrow derived hematopoietic stem cells (HSC-BM. Neuronal stem cells expressed β-3 tubulin and glial fibrillary acid protein which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum was infused under local anesthesia in right brachial plexus sheath by brachial block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge needle. Nucleated cell count was 2 × 10 4 /μl, CD34+ was 0.06%, and CD45-/90+ and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were noted. He has sustained recovery with re-innervation over a follow-up of 4 years documented on electromyography-nerve conduction velocity study.

  12. Conditioned Media from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Umbilical Cord-Derived Mesenchymal Stem Cells Efficiently Induced the Apoptosis and Differentiation in Human Glioma Cell Lines In Vitro

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2014-01-01

    Full Text Available Human mesenchymal stem cells (MSCs have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs. We found (1 MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2 MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3 real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4 furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.

  13. The Adipose Tissue in Farm Animals

    DEFF Research Database (Denmark)

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura

    2014-01-01

    and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in farm animal adipose tissue proteomics, mainly in cattle and pigs, but also in poultry, i.e. chicken and in farmed fish. Proteomics...... and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance...... in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal...

  14. Conditioned Medium from Adipose Tissue-Derived Mesenchymal Stem Cells Induces CD4+FOXP3+ Cells and Increases IL-10 Secretion

    Directory of Open Access Journals (Sweden)

    Ekaterina Ivanova-Todorova

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs are a new and promising tool for therapy of autoimmune disorders. In recent years their possibility to take part in the modulation of the immune response is discussed. The exact mechanisms for immunoregulation realized by MSCs are not clear yet, but interactions with other immunoregulatory cells may be involved in this process. The investigation of the influence of MSCs on the expression of FoxP3 and cytokine secretion by T helper cells was the aim of this study. T helper cells were isolated from PBMCs by magnetic separation and MSCs were isolated from human adipose tissue, and CD4+ T cells were cultured with conditional medium of MSCs. The methods which were used include flow cytometry, ELISA, and Human Proteome profiler kits. The results demonstrated that secretory factors in MSCs conditional medium lead to increased expression of FoxP3 and increased secretion of IL-10 by T helpers. The obtained results give us opportunity to discuss the interaction between two kinds of immunoregulatory cells: MSCs and FoxP3+ T helpers. We suppose that this interaction leads to increased number of immunosuppressive helpers which secrete IL-10. MSCs provide some of their immunosuppressive functions acting on T regulatory cells, and we believe that IL-6 secreted by MSCs is involved in this process.

  15. Pharmacological and non-pharmacological interventions to influence adipose tissue function

    Directory of Open Access Journals (Sweden)

    Visseren Frank LJ

    2011-01-01

    Full Text Available Abstract Obesity is associated with metabolic derangements such as insulin resistance, inflammation and hypercoagulobility which can all be understood as consequences of adipose tissue dysfunction. The potential role for adipose tissue derived cytokines and adipokines in the development of vascular disease and diabetes may produce a clinical need to influence adipose tissue function. Various pharmacological and non-pharmacological interventions affect plasma cytokine and adipokine levels. The effects of these interventions depend on weight loss per se, changes in fat distribution without weight loss and/or direct effects on adipose tissue inflammation. Weight loss, as a result of diet, pharmacology and surgery, positively influences plasma adipokines and systemic inflammation. Several classes of drugs influence systemic inflammation directly through their anti-inflammatory actions. PPAR-γ agonism positively influences adipose tissue inflammation in several classes of intervention such as the thiazolidinediones and perhaps salicylates, CB1-antagonists and angiotensin II receptor blockers. Furthermore, within drug classes there are differential effects of individual pharmacologic agents on adipose tissue function. It can be concluded that several commonly used pharmacological and non-pharmacological interventions have unintended influences on adipose tissue function. Improving adipose tissue function may contribute to reducing the risk of vascular diseases and the development of type 2 diabetes.

  16. Biosynthesis of collagen I, II, RUNX2 and lubricin at different time points of chondrogenic differentiation in a 3D in vitro model of human mesenchymal stem cells derived from adipose tissue.

    Science.gov (United States)

    Musumeci, Giuseppe; Mobasheri, Ali; Trovato, Francesca Maria; Szychlinska, Marta Anna; Graziano, Adriana Carol Eleonora; Lo Furno, Debora; Avola, Rosanna; Mangano, Sebastiano; Giuffrida, Rosario; Cardile, Venera

    2014-10-01

    The first aim of the study was to identify the most appropriate time for differentiation of adipose tissue derived mesenchymal stem cells (MSCs) to chondrocytes, through the self-assembly process. For this purpose, the expression of some chondrocyte markers, such as collagen type I, collagen type II, RUNX2 and lubricin was investigated at different times (7, 14, 21 and 28 days) of chondrogenic differentiation of MSCs, by using immunohistochemistry and Western blot analysis. The second aim of the study was to demonstrate that the expression of lubricin, such as the expression of collagen type II, could be a possible biomarker for the detection of chondrocytes well-being and viability in the natural self-assembling constructs, called 'cell pellets'. Histology (hematoxylin and eosin) and histochemistry (alcian blue staining) methods were used to assess the chondrogenic differentiation of MSCs. The results showed that after 21 days the differentiated chondrocytes, when compared with MSCs cultured without chondrogenic medium (CD44, CD90 and CD105 positive; CD45, CD14 and CD34 negative), were able to produce significant quantities of collagen type I, collagen type II, and lubricin, suggesting hyaline cartilage formation. During the differentiation phase, the cells showed a reduced expression of RUNX2, a protein expressed by osteoblasts. Our studies demonstrated that 21 days is the optimum time for the implantation of chondrocytes differentiated from adipose tissue-derived MSCs. This information could be useful for the future development of cell-based repair therapies for degenerative diseases of articular cartilage. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Mechanical homeostasis regulating adipose tissue volume

    Directory of Open Access Journals (Sweden)

    Svedman Paul

    2007-09-01

    Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

  18. Evaluation of the effects of different culture media on the myogenic differentiation potential of adipose tissue- or bone marrow-derived human mesenchymal stem cells.

    Science.gov (United States)

    Stern-Straeter, Jens; Bonaterra, Gabriel Alejandro; Juritz, Stephanie; Birk, Richard; Goessler, Ulrich Reinhart; Bieback, Karen; Bugert, Peter; Schultz, Johannes; Hörmann, Karl; Kinscherf, Ralf; Faber, Anne

    2014-01-01

    The creation of functional muscles/muscle tissue from human stem cells is a major goal of skeletal muscle tissue engineering. Mesenchymal stem cells (MSCs) from fat/adipose tissue (AT-MSCs), as well as bone marrow (BM-MSCs) have been shown to bear myogenic potential, which makes them candidate stem cells for skeletal muscle tissue engineering applications. The aim of this study was to analyse the myogenic differentiation potential of human AT-MSCs and BM-MSCs cultured in six different cell culture media containing different mixtures of growth factors. The following cell culture media were used in our experiments: mesenchymal stem cell growth medium (MSCGM)™ as growth medium, MSCGM + 5-azacytidine (5-Aza), skeletal muscle myoblast cell growth medium (SkGM)-2 BulletKit™, and 5, 30 and 50% conditioned cell culture media, i.e., supernatant of human satellite cell cultures after three days in cell culture mixed with MSCGM. Following the incubation of human AT-MSCs or BM-MSCs for 0, 4, 8, 11, 16 or 21 days with each of the cell culture media, cell proliferation was measured using the alamarBlue® assay. Myogenic differentiation was evaluated by quantitative gene expression analyses, using quantitative RT-PCR (qRT-PCR) and immunocytochemical staining (ICC), using well-defined skeletal markers, such as desmin (DES), myogenic factor 5 (MYF5), myosin, heavy chain 8, skeletal muscle, perinatal (MYH8), myosin, heavy chain 1, skeletal muscle, adult (MYH1) and skeletal muscle actin-α1 (ACTA1). The highest proliferation rates were observed in the AT-MSCs and BM-MSCs cultured with SkGM-2 BulletKit medium. The average proliferation rate was higher in the AT-MSCs than in the BM-MSCs, taking all six culture media into account. qRT-PCR revealed the expression levels of the myogenic markers, ACTA1, MYH1 and MYH8, in the AT-MSC cell cultures, but not in the BM-MSC cultures. The muscle-specific intermediate filament, DES, was only detected (by ICC) in the AT-MSCs, but not in the BM

  19. Comparative Analyses of Immunosuppressive Characteristics of Bone-Marrow, Wharton’s Jelly, and Adipose Tissue-Derived Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Erdal Karaöz

    2017-09-01

    Full Text Available Objective: Mesenchymal stem cells (MSCs, which possess immunosuppressive characteristics on induced T-cells, were shown to be applicable in prevention and treatment of graft-versus-host disease. However, knowledge of effective cell sources is still limited. In this study, MSCs from different human tissues, i.e. bone marrow (BM, Wharton’s jelly (WJ, and adipose tissue, were isolated, and the immune suppression of stimulated T cells was analyzed comparatively. Materials and Methods: MSCs were co-cultured with phytohemagglutinin-induced T-cells with co-culture techniques with and without cell-to-cell contact. After co-culture for 24 and 96 h, the proliferation rate of T cells was estimated by carboxyfluorescein succinimidyl ester and apoptosis by annexin V/PI methods. Both T cells and MSCs were analyzed with respect to gene expressions by real-time polymerase chain reaction and their specific protein levels by ELISA. Results: The results showed that all three MSC lines significantly suppressed T-cell proliferation; BM-MSCs were most effective. Similarly, T-cell apoptosis was induced most strongly by BM-MSCs in indirect culture. In T cells, the genes in NFkB and tumor necrosis factor pathways were silenced and the caspase pathway was induced after co-culture. These results were confirmed with the measurement of protein levels, like transforming growth factor β1, IL-6, interferon-γ, interleukin (IL-2, and tumor necrosis factor-α. Additionally, IL-17A was detected in high levels in WJ-MSC co-cultures. We showed that IL-17A-producing Tregs are the key mediators in the treatment of graft-versus-host disease. Conclusion: BM-MSCs, which have been used in clinical applications for a while, showed the greatest immunosuppressive effect compared to other MSCs. However, a promising cell source could also be WJ, which is also effective in suppression with fewer ethical concerns. We described the molecular mechanism of WJ-MSCs in allogenic transplants for

  20. Aetiological factors behind adipose tissue inflammation

    DEFF Research Database (Denmark)

    von Scholten, Bernt J; Andresen, Erik N; Sørensen, Thorkild I A

    2013-01-01

    Despite extensive research into the biological mechanisms behind obesity-related inflammation, knowledge of environmental and genetic factors triggering such mechanisms is limited. In the present narrative review we present potential determinants of adipose tissue inflammation and suggest ways...

  1. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-08-01

    Full Text Available BACKGROUND: Over the past 50 years, scientists have recognized that not all adipose tissue is alike, and that health risk is associated with the location as well as the amount of body fat. Different depots are sufficiently distinct with respect to fatty-acid storage and release as to probably play unique roles in human physiology. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. CONTENT: The limited expandability of the subcutaneous adipose tissue leads to inappropriate adipose cell expansion (hypertrophic obesity with local inflammation and a dysregulated and insulin-resistant adipose tissue. The inability to store excess fat in the subcutaneous adipose tissue is a likely key mechanism for promoting ectopic fat accumulation in tissues and areas where fat can be stored, including the intra-abdominal and visceral areas, in the liver, epi/pericardial area, around vessels, in the myocardium, and in the skeletal muscles. Many studies have implicated ectopic fat accumulation and the associated lipotoxicity as the major determinant of the metabolic complications of obesity driving systemic insulin resistance, inflammation, hepatic glucose production, and dyslipidemia. SUMMARY: In summary, hypertrophic obesity is due to an impaired ability to recruit and differentiate available adipose precursor cells in the subcutaneous adipose tissue. Thus, the subcutaneous adipose tissue may be particular in its limited ability in certain individuals to undergo adipogenesis during weight increase. Inability to promote subcutaneous adipogenesis under periods of affluence would favor lipid overlow and ectopic fat accumulation with negative metabolic consequences. KEYWORDS: obesity, adipogenesis, subcutaneous adipose tissue, visceral adipose tissue, adipocyte dysfunction.

  2. Influencing Factors of Thermogenic Adipose Tissue Activity.

    Science.gov (United States)

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called "brite" or "beige" adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases.

  3. HIV Persistence in Adipose Tissue Reservoirs.

    Science.gov (United States)

    Couturier, Jacob; Lewis, Dorothy E

    2018-02-01

    The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

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

    Science.gov (United States)

    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

  5. Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load

    DEFF Research Database (Denmark)

    Bülow, J; Astrup, A; Christensen, N J

    1987-01-01

    Blood flow to the forearm, and the subcutaneous tissue and skin in the forearm were measured by strain gauge plethysmography, 133Xe-elimination and Laser Doppler flowmetry during an oral glucose load (I g glucose kg-1 lean body mass) and during control conditions. The forearm blood flow remained......, muscle blood flow decreased about 20-30% during both experiments. Proximal nervous blockade did not abolish the glucose-induced vasodilatation in subcutaneous tissue. In the glucose experiment, arterial glucose concentration increased to 7.8 +/- 1.17 mmol l-1 30 min after the load was given...... constant during both experiments. Glucose induced a two-fold vasodilatation in subcutaneous tissue. In skin, glucose induced a relative vasodilatation and later a relative vasoconstriction compared with control experiments. When estimated from forearm blood flow and subcutaneous and skin blood flows...

  6. 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...

  7. Labeling and in vivo visualization of transplanted adipose tissue-derived stem cells with safe cadmium-free aqueous ZnS coating of ZnS-AgInS2nanoparticles.

    Science.gov (United States)

    Ogihara, Yusuke; Yukawa, Hiroshi; Kameyama, Tatsuya; Nishi, Hiroyasu; Onoshima, Daisuke; Ishikawa, Tetsuya; Torimoto, Tsukasa; Baba, Yoshinobu

    2017-01-06

    The facile synthesis of ZnS-AgInS 2 (ZAIS) as cadmium-free QDs and their application, mainly in solar cells, has been reported by our groups. In the present study, we investigated the safety and the usefulness for labeling and in vivo imaging of a newly synthesized aqueous ZnS-coated ZAIS (ZnS-ZAIS) carboxylated nanoparticles (ZZC) to stem cells. ZZC shows the strong fluorescence in aqueous solutions such as PBS and cell culture medium, and a complex of ZZC and octa-arginine (R8) peptides (R8-ZZC) can achieve the highly efficient labeling of adipose tissue-derived stem cells (ASCs). The cytotoxicity of R8-ZZC to ASCs was found to be extremely low in comparison to that of CdSe-based QDs, and R8-ZZC was confirmed to have no influence on the proliferation rate or the differentiation ability of ASCs. Moreover, R8-ZZC was not found to induce the production of major inflammatory cytokines (TNF-α, IFN-γ, IL-12p70, IL-6 and MCP-1) in ASCs. Transplanted R8-ZZC-labeled ASCs could be quantitatively detected in the lungs and liver mainly using an in vivo imaging system. In addition, high-speed multiphoton confocal laser microscopy revealed the presence of aggregates of transplanted ASCs at many sites in the lungs, whereas individual ASCs were found to have accumulated in the liver.

  8. 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.

  9. Labeling and in vivo visualization of transplanted adipose tissue-derived stem cells with safe cadmium-free aqueous ZnS coating of ZnS-AgInS2 nanoparticles

    Science.gov (United States)

    Ogihara, Yusuke; Yukawa, Hiroshi; Kameyama, Tatsuya; Nishi, Hiroyasu; Onoshima, Daisuke; Ishikawa, Tetsuya; Torimoto, Tsukasa; Baba, Yoshinobu

    2017-01-01

    The facile synthesis of ZnS-AgInS2 (ZAIS) as cadmium-free QDs and their application, mainly in solar cells, has been reported by our groups. In the present study, we investigated the safety and the usefulness for labeling and in vivo imaging of a newly synthesized aqueous ZnS-coated ZAIS (ZnS-ZAIS) carboxylated nanoparticles (ZZC) to stem cells. ZZC shows the strong fluorescence in aqueous solutions such as PBS and cell culture medium, and a complex of ZZC and octa-arginine (R8) peptides (R8-ZZC) can achieve the highly efficient labeling of adipose tissue-derived stem cells (ASCs). The cytotoxicity of R8-ZZC to ASCs was found to be extremely low in comparison to that of CdSe-based QDs, and R8-ZZC was confirmed to have no influence on the proliferation rate or the differentiation ability of ASCs. Moreover, R8-ZZC was not found to induce the production of major inflammatory cytokines (TNF-α, IFN-γ, IL-12p70, IL-6 and MCP-1) in ASCs. Transplanted R8-ZZC-labeled ASCs could be quantitatively detected in the lungs and liver mainly using an in vivo imaging system. In addition, high-speed multiphoton confocal laser microscopy revealed the presence of aggregates of transplanted ASCs at many sites in the lungs, whereas individual ASCs were found to have accumulated in the liver.

  10. Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity

    Directory of Open Access Journals (Sweden)

    William Trim

    2018-02-01

    Full Text Available Ageing, like obesity, is often associated with alterations in metabolic and inflammatory processes resulting in morbidity from diseases characterised by poor metabolic control, insulin insensitivity, and inflammation. Ageing populations also exhibit a decline in immune competence referred to as immunosenescence, which contributes to, or might be driven by chronic, low-grade inflammation termed “inflammageing”. In recent years, animal and human studies have started to uncover a role for immune cells within the stromal fraction of adipose tissue in driving the health complications that come with obesity, but relatively little work has been conducted in the context of immunometabolic adipose function in ageing. It is now clear that aberrant immune function within adipose tissue in obesity—including an accumulation of pro-inflammatory immune cell populations—plays a major role in the development of systemic chronic, low-grade inflammation, and limiting the function of adipocytes leading to an impaired fat handling capacity. As a consequence, these changes increase the chance of multiorgan dysfunction and disease onset. Considering the important role of the immune system in obesity-associated metabolic and inflammatory diseases, it is critically important to further understand the interplay between immunological processes and adipose tissue function, establishing whether this interaction contributes to age-associated immunometabolic dysfunction and inflammation. Therefore, the aim of this article is to summarise how the interaction between adipose tissue and the immune system changes with ageing, likely contributing to the age-associated increase in inflammatory activity and loss of metabolic control. To understand the potential mechanisms involved, parallels will be drawn to the current knowledge derived from investigations in obesity. We also highlight gaps in research and propose potential future directions based on the current evidence.

  11. Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects

    DEFF Research Database (Denmark)

    Asmar, M; Simonsen, L; Arngrim, N

    2013-01-01

    OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested...... that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism would...... to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI...

  12. Omental adipose tissue is a more suitable source of canine Mesenchymal stem cells.

    Science.gov (United States)

    Bahamondes, Francisca; Flores, Estefania; Cattaneo, Gino; Bruna, Flavia; Conget, Paulette

    2017-06-08

    Mesenchymal Stem Cells (MSCs) are a promising therapeutic tool in veterinary medicine. Currently the subcutaneous adipose tissue is the leading source of MSCs in dogs. MSCs derived from distinct fat depots have shown dissimilarities in their accessibility and therapeutic potential. The aims of our work were to determine the suitability of omental adipose tissue as a source of MSCs, according to sampling success, cell yield and paracrine properties of isolated cells, and compared to subcutaneous adipose tissue. While sampling success of omental adipose tissue was 100% (14 collections from14 donors) for subcutaneous adipose tissue it was 71% (10 collections from 14 donors). MSCs could be isolated from both sources. Cell yield was significantly higher for omental than for subcutaneous adipose tissue (38 ± 1 vs. 30 ± 1 CFU-F/g tissue, p cell proliferation potential (73 ± 1 vs. 74 ± 1 CDPL) and cell senescence (at passage 10, both cultures presented enlarged cells with cytoplasmic vacuoles and cellular debris). Omental- and subcutaneous-derived MSCs expressed at the same level bFGF, PDGF, HGF, VEGF, ANG1 and IL-10. Irrespective of the source, isolated MSCs induced proliferation, migration and vascularization of target cells, and inhibited the activation of T lymphocytes. Compared to subcutaneous adipose tissue, omental adipose tissue is a more suitable source of MSCs in dogs. Since it can be procured from donors with any body condition, its collection procedure is always feasible, its cell yield is high and the MSCs isolated from it have desirable differentiation and paracrine potentials.

  13. 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.

  14. 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

    DEFF Research Database (Denmark)

    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...

  15. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andrew A. Bremer

    2013-01-01

    Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

  16. Insulin resistance causes inflammation in adipose tissue.

    Science.gov (United States)

    Shimobayashi, Mitsugu; Albert, Verena; Woelnerhanssen, Bettina; Frei, Irina C; Weissenberger, Diana; Meyer-Gerspach, Anne Christin; Clement, Nicolas; Moes, Suzette; Colombi, Marco; Meier, Jerome A; Swierczynska, Marta M; Jenö, Paul; Beglinger, Christoph; Peterli, Ralph; Hall, Michael N

    2018-03-12

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

  17. Cardio-adipose tissue cross-talk

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan Skov; Bjerre, Mette

    2014-01-01

    increases adiponectin secretion, indicating that NPs may improve adipose tissue function and in this way function as a cardio-protective agent in HF. Accordingly we investigated the interplay between plasma adiponectin, plasma proBNP, and development of HF. METHODS AND RESULTS: We prospectively followed...

  18. Mycobacterium canettii Infection of Adipose Tissues.

    Science.gov (United States)

    Bouzid, Fériel; Brégeon, Fabienne; Poncin, Isabelle; Weber, Pascal; Drancourt, Michel; Canaan, Stéphane

    2017-01-01

    Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii , a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18-22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii ( p = 0.02) and M. tuberculosis ( p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis ( p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii , it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.

  19. Browning and thermogenic programing of adipose tissue.

    Science.gov (United States)

    Kiefer, Florian W

    2016-08-01

    The view of adipose tissue as solely a fat storing organ has changed significantly over the past two decades with the discoveries of numerous adipocyte-secreted factors, so called adipokines, and their endocrine functions throughout the body. The newest chapter added to this story is the finding that adipose tissue is also a thermogenic organ contributing to energy expenditure through actions of specialized, heat-producing brown or beige adipocytes. In contrast to bone fide brown adipocytes, beige cells develop within white fat depots in response to various stimuli such as prolonged cold exposure, underscoring the great thermogenic plasticity of adipose tissue. The energy dissipating properties of beige and/or brown adipocytes hold great promise as a novel therapeutic concept against obesity and related complications. Hence, identifying the specific thermogenic adipocyte populations in humans and their pathways of activation are key milestones of current metabolism research. Here we will discuss the recent advances in the understanding of the molecular and physiological mechanisms of adipose tissue browning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 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

    DEFF Research Database (Denmark)

    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...... ventricle ejection fraction, myocardial mass, stroke volume, and cardiac output. Other secondary endpoints are change in clinical symptoms, 6-minute walking test, and the quality of life after 6 and 12 months. CONCLUSION: The aim of the present study is to demonstrate safety and the regenerative efficacy...

  1. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ra Jeong Chan

    2011-10-01

    Full Text Available Abstract Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

  2. Conventional vs. micro-fat harvesting: how fat harvesting technique affects tissue-engineering approaches using adipose tissue-derived stem/stromal cells.

    Science.gov (United States)

    Alharbi, Ziyad; Opländer, Christian; Almakadi, Sultan; Fritz, Andrea; Vogt, Michael; Pallua, Norbert

    2013-09-01

    Biocompatible scaffolds as dermal substitutes are used commonly in soft tissue reconstruction and tissue-engineering approaches. The combination of these scaffolds with mesenchymal stem and stromal cells would have additional benefits in multilayer soft tissue reconstruction. In addition, the use of lipoaspirate may be beneficial for this purpose containing high levels of regenerative cells and relevant growth factors. However there are many factors, which may impact the lipoaspirate content of isolated cells, cell behaviour and growth factors. There is a lack of data as to whether fat-harvesting procedures using different cannulas of small diameter will impact these parameters, which are relevant not only for tissue engineering but also for clinical outcome. Abdominal liposuctions were performed on 10 patients using the conventional fat harvesting by the Coleman cannula (3 mm, one-hole blunt tip) and the micro-fat-harvesting technique by the st'RIM cannula (2 mm, multi-perforated hole blunt tip) on contralateral area. Lipoaspirate contents of insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were measured by enzyme-linked immunosorbent assay (ELISA). The in vitro viability of lipoaspirates was tested by the alamarBlue™ assay. Adipose-derived stem/stromal cells (ASCs) were isolated and the yields determined. Furthermore, ACSs were seeded on collagen elastin matrices (Matriderm™) and cell migration/adhesion rate was examined by the alamarBlue™ assay and visualised by two-photon microscopy. Conventionally obtained lipoaspirates were found to contain significantly higher concentrations of IGF and VEGF, but not PDGF or bFGF. No significant effects on the yields of ASCs or the in vitro viability of lipoaspirates obtained from different cannula sizes were observable. However, the viability and migration of isolated ASCs obtained from micro

  3. Effects of different concentrations of Platelet-rich Plasma and Platelet-Poor Plasma on vitality and differentiation of autologous Adipose tissue-derived stem cells.

    Science.gov (United States)

    Felthaus, Oliver; Prantl, Lukas; Skaff-Schwarze, Mona; Klein, Silvan; Anker, Alexandra; Ranieri, Marco; Kuehlmann, Britta

    2017-01-01

    Autologous fat grafts and adipose-derived stem cells (ASCs) can be used to treat soft tissue defects. However, the results are inconsistent and sometimes comprise tissue resorption and necrosis. This might be due to insufficient vascularization. Platelet-rich plasma (PRP) is a source of concentrated autologous platelets. The growth factors and cytokines released by platelets can facilitate angiogenesis. The simultaneous use of PRP might improve the regeneration potential of fat grafts. The optimal ratio has yet to be elucidated. A byproduct of PRP preparation is platelet-poor plasma (PPP). In this study we investigated the influence of different concentrations of PRP on the vitality and differentiation of ASCs. We processed whole blood with the Arthrex Angel centrifuge and isolated ASCs from the same donor. We tested the effects of different PRP and PPP concentrations on the vitality using resazurin assays and the differentiation of ASCs using oil-red staining. Both cell vitality and adipogenic differentiation increase to a concentration of 10% to 20% PRP. With a PRP concentration of 30% cell vitality and differentiation decrease. Both PRP and PPP can be used to expand ASCs without xenogeneic additives in cell culture. A PRP concentration above 20% has inhibitory effects.

  4. Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial.

    Science.gov (United States)

    Riester, Scott M; Denbeigh, Janet M; Lin, Yang; Jones, Dakota L; de Mooij, Tristan; Lewallen, Eric A; Nie, Hai; Paradise, Christopher R; Radel, Darcie J; Dudakovic, Amel; Camilleri, Emily T; Larson, Dirk R; Qu, Wenchun; Krych, Aaron J; Frick, Matthew A; Im, Hee-Jeong; Dietz, Allan B; Smith, Jay; van Wijnen, Andre J

    2017-03-01

    Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x-ray, magnetic resonance imaging, and histopathology. Intra-articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra-articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910-922. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  5. A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial.

    Science.gov (United States)

    Sarveazad, Arash; Newstead, Graham L; Mirzaei, Rezvan; Joghataei, Mohammad Taghi; Bakhtiari, Mehrdad; Babahajian, Asrin; Mahjoubi, Bahar

    2017-02-21

    Anal sphincter defects are a major cause of fecal incontinence causing negative effects on daily life, social interactions, and mental health. Because human adipose-derived stromal/stem cells (hADSCs) are easier and safer to access, secrete high levels of growth factor, and have the potential to differentiate into muscle cells, we investigated the ability of hADSCs to improve anal sphincter incontinence. The present randomized double-blind clinical trial was performed on patients with sphincter defects. They were categorized into a cell group (n = 9) and a control group (n = 9). Either 6 × 10 6 hADSCs per 3 ml suspended in phosphate buffer saline (treatment) or 3 ml phosphate buffer saline (placebo) was injected. Two months after surgery, the Wexner score, endorectal sonography, and electromyography (EMG) results were recorded. Comparing Wexner scores in the cell group and the control group showed no significant difference. In our EMG and endorectal sonography analysis using ImageJ/Fiji 1.46 software, the ratio of the area occupied by the muscle to total area of the lesion showed a 7.91% increase in the cell group compared with the control group. The results of the current study show that injection of hADSCs during repair surgery for fecal incontinence may cause replacement of fibrous tissue, which acts as a mechanical support to muscle tissue with contractile function. This is a key point in treatment of fecal incontinence especially in the long term and may be a major step forward. Iranian Registry of Clinical Trials IRCT2016022826316N2 . Retrospectively registered 7 May 2016.

  6. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    Science.gov (United States)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L.; Gomes, Manuela E.

    2015-11-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages.

  7. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    Energy Technology Data Exchange (ETDEWEB)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L. [3Bs Research Group–Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães (Portugal); ICVS/3Bs–PT Government Associate Laboratory, Braga/Guimarães (Portugal); Gomes, Manuela E., E-mail: megomes@dep.uminho.pt [3Bs Research Group–Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães (Portugal); ICVS/3Bs–PT Government Associate Laboratory, Braga/Guimarães (Portugal)

    2015-11-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages. - Highlights: • Cellular viability was not negatively influenced by the nanoparticles. • Chondrogenic medium influences more the synthesis of cartilage-like ECM than MNPs. • Synergetic effect among

  8. Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage.

    Directory of Open Access Journals (Sweden)

    Jae-Yol Lim

    Full Text Available OBJECTIVES: Cell-based therapy has been reported to repair or restore damaged salivary gland (SG tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs can ameliorate radiation-induced SG damage. METHODS: hAdMSCs (1 × 10(6 were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs was observed in vitro using a co-culture system. RESULTS: The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18% were observed to transdifferentiate into SGCs. CONCLUSION: The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.

  9. Zinc Sulphate Mediates the Stimulation of Cell Proliferation of Rat Adipose Tissue-Derived Mesenchymal Stem Cells Under High Intensity of EMF Exposure.

    Science.gov (United States)

    Fathi, Ezzatollah; Farahzadi, Raheleh

    2017-11-30

    Unlike the role of mesenchymal stem cells (MSCs) in regenerative medicine, their application in cell therapy can be complicated by factors such as a reduction in the proliferation potential, senescent tendency of MSCs to expand, and an age-dependent decline in their number and functions. It was shown that there is an association between exposure to electromagnetic fields (EMFs) and response to stress, cell proliferation, aging, and cell death. Furthermore, the zinc ion, as an essential trace element, was reported to be involved in the regulation of the growth and cell proliferation. In this report, ratadipose tissue-derived mesenchymal stem cells (rADSCs) were randomly divided into four groups-group I (control without any ZnSO 4 and EMF); group II (ZnSO 4 treatment without EMF exposed); group III (EMF exposed without ZnSO 4 ); and group ІV (EMF exposed with ZnSO 4 )-to evaluate whether 0.14 μg/ml Zinc sulfate (ZnSO 4 ) could affect cell proliferation of rADSCs under extremely low frequency-electromagnetic field (ELF-EMF). The methyl thiazoltetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to ELF-EMF in the presence of ZnSO 4 . The immunocytochemistry method as well as flow-cytometry was used to identify the cell surface markers. Next, oil red O, alizarin red, toluidine blue, and cresyl violet staining was done to evaluate the adipogenic, osteogenic, chondrogenic, and neurogenic differentiation of rADSCs as the pluripotent capacity of rADSCs, respectively. The results showed that an exposure to ELF-EMF caused a decrease in the proliferation of rADSCs. However, the ZnSO 4 supplementation significantly increased the cell proliferation of ELF-EMF-exposed rADSCs. In addition, in the presence of 0.14 μg/ml ZnSO 4 , rADSCs appeared to be growing faster than the control group and ZnSO 4 significantly decreased the doubling time of ELF-EMF-exposed rADSCs. It seems that ZnSO 4 would be a good element to induce the cell

  10. Enhancement of osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells by zinc sulphate under electromagnetic field via the PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

    Directory of Open Access Journals (Sweden)

    Ezzatollah Fathi

    Full Text Available Zinc ion as an essential trace element and electromagnetic fields (EMFs has been reported to be involved in the regulation of bone metabolism. The aim of this study was to elucidate the effects of zinc sulphate (ZnSO4 on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs in the presence of EMF as a strategy in osteoporosis therapy. Alkaline phophatase (ALP activity measurement, calcium assay and expression of several osteoblastic marker genes were examined to assess the effect of ZnSO4 on the osteogenic differentiation of ADSCs under EMF. The expression of cAMP and PKA was evaluated by ELISA. The expression of β-catenin, Wnt1, Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5 and reduced dickkopf1 (DKK1 genes were used to detect the Wnt/β-catenin pathway. It was found that ZnSO4, in the presence of EMF, resulted in an increase in the expression of osteogenic genes, ALP activity and calcium levels. EMF, in the presence of ZnSO4, increased the cAMP level and protein kinase A (PKA activity. Treatment of ADSCs with (MAPK/ERK kinase 1/2 inhibitor, or PKA inhibitor, significantly inhibited the promotion of osteogenic markers, indicating that the induction of osteogenesis was dependent on the ERK and PKA signaling pathways. Real-time PCR analysis showed that ZnSO4, in the presence of EMF, increased the mRNA expressions of β-catenin, Wnt1, Wnt3a, LRP5 and DKK1. In this study, it was shown that 0.432 μg/ml ZnSO4, in the presence of 50 Hz, 20 mT EMF, induced the osteogenic differentiation of ADSCs via PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

  11. Cardio-adipose tissue cross-talk

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan Skov; Bjerre, Mette

    2014-01-01

    AIMS: There is increasing evidence of cross-talk between the heart, body metabolism, and adipose tissue, but the precise mechanisms are poorly understood. Natriuretic peptides (NPs) have recently emerged as the prime candidate for a mediator. In patients with heart failure (HF), infusion of NPs...... increases adiponectin secretion, indicating that NPs may improve adipose tissue function and in this way function as a cardio-protective agent in HF. Accordingly we investigated the interplay between plasma adiponectin, plasma proBNP, and development of HF. METHODS AND RESULTS: We prospectively followed...... and diastolic blood pressure, lipid profile, high sensitivity C-reactive protein, estimated glomerular filtration rate, and physical activity) by Cox regression analysis, adiponectin remained an independent predictor of HF: the hazard ratio (HR) per 1 standard deviation (SD) increase in adiponectin was 1.20 [95...

  12. [Differentiation of mesenchymal stem cells of adipose tissue].

    Science.gov (United States)

    Salyutin, R V; Zapohlska, K M; Palyanytsya, S S; Sirman, V M; Sokolov, M F

    2015-03-01

    Experimental investigation were conducted with the objective to determine a stem cells, capacity to differentiate in adipogenic direction, if they were obtained from adipose tissue. The investigation results have witnessed, that the cells, obtained from adipose tissue, are capable for a tissue-speciphic differentiation in osteogenic, chondrogenic, and, principally--in adipogenic direction, what confirms a multypotent nature of mesenchymal stem cells of adipose tissue. Adipose tissue constitutes an alternative to the bone marrow, as a source of multipotent mesenchymal stem cells, which may be applied in further investigations, concerning determination of their defense possibility for the transplanted autologous adipose tissue from the tissue resorption, made in a lipophiling way.

  13. Peptides from adipose tissue in mental disorders

    OpenAIRE

    Wędrychowicz, Andrzej; Zając, Andrzej; Pilecki, Maciej; Kościelniak, Barbara; Tomasik, Przemysław J

    2014-01-01

    Adipose tissue is a dynamic endocrine organ that is essential to regulation of metabolism in humans. A new approach to mental disorders led to research on involvement of adipokines in the etiology of mental disorders and mood states and their impact on the health status of psychiatric patients, as well as the effects of treatment for mental health disorders on plasma levels of adipokines. There is evidence that disturbances in adipokine secretion are important in the pathogenesis, clinical pr...

  14. 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

  15. Glucocorticoids Suppress the Browning of Adipose Tissue via miR-19b in Male Mice.

    Science.gov (United States)

    Lv, Yi-Fan; Yu, Jing; Sheng, Yun-Lu; Huang, Min; Kong, Xiao-Cen; Di, Wenj-Juan; Liu, Juan; Zhou, Hong; Liang, Hui; Ding, Guo-Xian

    2018-01-01

    Physiological levels of glucocorticoids (GCs) are required for proper metabolic control, and excessive GC action has been linked to a variety of pandemic metabolic diseases. MicroRNA (miRNA)-19b plays a critical role in the pathogenesis of GC-induced metabolic diseases. This study explored the potential of miRNA-based therapeutics targeting adipose tissue. Our results showed that overexpressed miR-19b in stromal vascular fraction (SVF) cells derived from subcutaneous adipose tissue had the same effects as dexamethasone (DEX) treatment on the inhibition of adipose browning and oxygen consumption rate. The inhibition of miR-19b blocked DEX-mediated suppression of the expression of browning marker genes as well as the oxygen consumption rate in differentiated SVF cells derived from subcutaneous and brown adipose tissue. Overexpressed miR-19b in SVF cells derived from brown adipose tissue had the same effects as DEX treatment on the inhibition of brown adipose differentiation and energy expenditure. Glucocorticoids transcriptionally regulate the expression of miR-19b via a GC receptor-mediated direct DNA binding mechanism. This study confirmed that miR-19b is an essential target for GC-mediated control of adipose tissue browning. It is hoped that the plasticity of the adipose organ can be exploited in the next generation of therapeutic strategies to combat the increasing incidence of metabolic diseases, including obesity and diabetes. Copyright © 2018 Endocrine Society.

  16. Does bariatric surgery improve adipose tissue function?

    Science.gov (United States)

    Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

    2017-01-01

    Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

  17. The Facial Adipose Tissue: A Revision.

    Science.gov (United States)

    Kruglikov, Ilja; Trujillo, Oscar; Kristen, Quick; Isac, Kerelos; Zorko, Julia; Fam, Maria; Okonkwo, Kasie; Mian, Asima; Thanh, Hyunh; Koban, Konstantin; Sclafani, Anthony P; Steinke, Hanno; Cotofana, Sebastian

    2016-12-01

    Recent advantages in the anatomical understanding of the face have turned the focus toward the subcutaneous and deep facial fat compartments. During facial aging, these fat-filled compartments undergo substantial changes along with other structures in the face. Soft tissue filler and fat grafting are valid methods to fight the signs of facial aging, but little is known about their precise effect on the facial fat. This narrative review summarizes the current knowledge about the facial fat compartments in terms of anatomical location, histologic appearance, immune-histochemical characteristics, cellular interactions, and therapeutic options. Three different types of facial adipose tissue can be identified, which are located either superficially (dermal white adipose tissue) or deep (subcutaneous white adipose tissue): fibrous (perioral locations), structural (major parts of the midface), and deposit (buccal fat pad and deep temporal fat pad). These various fat types differ in the size of the adipocytes and the collagenous composition of their extracellular matrix and thus in their mechanical properties. Minimal invasive (e.g., soft tissue fillers or fat grafting) and surgical interventions aiming to restore the youthful face have to account for the different fat properties in various facial areas. However, little is known about the macro- and microscopic characteristics of the facial fat tissue in different compartments and future studies are needed to reveal new insights to better understand the process of aging and how to fight its signs best. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Madsen, J

    1994-01-01

    A technique for catheterization of a vein draining abdominal subcutaneous tissue and a microdialysis technique that allows measurements of intercellular water concentrations in adipose tissue in humans have recently been described. In the present study, we compare the two techniques during an oral...

  19. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

    Directory of Open Access Journals (Sweden)

    Yumie Morimoto-Kobayashi

    Full Text Available Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA. Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional

  20. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong [State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Ma, Qinyun, E-mail: qinyunma@126.com [State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

  1. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-κB pathway

    International Nuclear Information System (INIS)

    Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong; Ma, Qinyun

    2012-01-01

    Highlights: ► Stevioside ameliorates high-fat diet-induced insulin resistance. ► Stevioside alleviates the adipose tissue inflammation. ► Stevioside reduces macrophages infiltration into the adipose tissue. ► Stevioside suppresses the activation of NF-κB in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-α, IL6, IL10, IL1β, KC, MIP-1α, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-κB) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-κB pathway.

  2. 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.

  3. Intratunical Injection of Genetically Modified Adipose Tissue-Derived Stem Cells with Human Interferon α-2b for Treatment of Erectile Dysfunction in a Rat Model of Tunica Albugineal Fibrosis.

    Science.gov (United States)

    Gokce, Ahmet; Abd Elmageed, Zakaria Y; Lasker, George F; Bouljihad, Mostafa; Braun, Stephen E; Kim, Hogyoung; Kadowitz, Philip J; Abdel-Mageed, Asim B; Sikka, Suresh C; Hellstrom, Wayne J

    2015-07-01

    Peyronie's disease (PD) has frequently been associated with erectile dysfunction (ED) and may further compromise coitus. To investigate the efficacy of intratunical injection of genetically modified rat adipose tissue-derived stem cells (ADSCs) expressing human interferon α-2b (ADSCs-IFN) in decreasing fibrosis and restoring erectile function in a rat model of tunica albugineal fibrosis (TAF). A total of 36 Sprague-Dawley rats (12 weeks old; 300-350 g) were randomly divided in six equal groups: (i) sham group (50 μL saline-injected into the tunica albuginea [TA]); (ii) TAF group (transforming growth factor [TGF]-β1 [0.5 μg/50 μL] injected into the TA); (iii) TGF-β1 plus 5 × 10(5) control ADSCs injected same day; (iv) TGF-β1 plus 5 × 10(5) ADSCs-IFN injected same day; (v) TGF-β1 plus 5 × 10(5) control ADSCs injected after 30 days; and (vi) TGF-β1 plus 5 × 10(5) ADSCs-IFN injected after 30 days. Rat allogeneic ADSCs were harvested from inguinal fat tissue. Forty-five days following the TGF-β1 injection, erectile function was assessed, and penile tissues were harvested for further evaluations. In the same-day injection groups, intratunical injection of ADSCs and ADSC-IFN improved erectile response observed upon stimulation of cavernous nerve compared with TAF group. Intratunical ADSC-IFN injection at day 30 improved erectile responses 3.1, 1.8, and 1.3 fold at voltages of 2.5, 5.0, and 7.0, respectively, when compared with TAF group. Furthermore, at voltages of 2.5 and 5.0, treatment on day 30 with ADSCs-IFN improved erectile responses 1.6- and 1.3-fold over treatment with ADSCs alone. Local injection of ADSCs or ADSCs-IFN reduced Peyronie's-like manifestations, and these effects might be associated with a decrease in the expression of tissue inhibitors of metalloproteinases. This study documents that transplantation of genetically modified ADSCs, with or without human IFN α-2b, attenuated Peyronie's-like changes and enhanced

  4. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okura, Hanayuki [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Saga, Ayami; Soeda, Mayumi [Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Miyagawa, Shigeru; Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Daimon, Takashi [Division of Biostatistics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Ichinose, Akihiro [Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); Matsuyama, Akifumi, E-mail: akifumi-matsuyama@umin.ac.jp [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); RIKEN Program for Drug Discovery and Medical Technology Platforms, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  5. Fish oil-derived long-chain n-3 polyunsaturated fatty acids reduce expression of M1-associated macrophage markers in an ex vivo adipose tissue culture model, in part through adiponectin

    Directory of Open Access Journals (Sweden)

    Anna A. De Boer

    2015-10-01

    Full Text Available Adipose tissue (AT macrophages (ATM play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad, may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil n-6 PUFA-rich diet or an isocaloric fish-oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM. We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute (18 h ACM plus LPS for the last 6 h or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2 and Ccl5 compared with CON ACM (p≤0.05; however, these effects were largely attenuated when Ad was neutralized (p>0.05. Further, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2 and Il1β and IL-6 and CCL2 secretion (p≤0.05; however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT inflammation.

  6. Fish Oil-Derived Long-Chain n-3 Polyunsaturated Fatty Acids Reduce Expression of M1-Associated Macrophage Markers in an ex vivo Adipose Tissue Culture Model, in Part through Adiponectin.

    Science.gov (United States)

    De Boer, Anna A; Monk, Jennifer M; Liddle, Danyelle M; Power, Krista A; Ma, David W L; Robinson, Lindsay E

    2015-01-01

    Adipose tissue (AT) macrophages (ATM) play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad), may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil) n-6 PUFA-rich diet or an isocaloric fish oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil)-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM). We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute [18 h ACM plus lipopolysaccharide (LPS) for the last 6 h] or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h) inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2, and Ccl5) compared with CON ACM (p ≤ 0.05); however, these effects were largely attenuated when Ad was neutralized (p > 0.05). Furthermore, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2, and Il1β) and IL-6 and CCL2 secretion (p ≤ 0.05); however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT

  7. 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.

    Science.gov (United States)

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

    2016-02-01

    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 this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Four adult warmblood horses received a unilateral injection of 10 × 10(6) autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 10(6) AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional

  8. Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

    Science.gov (United States)

    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.

  9. Lipolysis in human adipose tissue during exercise

    DEFF Research Database (Denmark)

    Lange, Kai Henrik Wiborg; Lorentsen, Jeanne; Isaksson, Fredrik

    2002-01-01

    exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue...... venous glycerol concentrations increased substantially from rest to exercise but were similar both at rest and during later stages of exercise. In contrast, during the initial approximately 40 min of exercise, calculated glycerol concentration was significantly lower (approximately 40%) than measured...... and continuous prolonged exercise. However, during shorter periods of exercise (

  10. Adipose tissue in muscle : a novel depot similar in size to visceral adipose tissue

    NARCIS (Netherlands)

    Gallagher, Dympna; Kuznia, Patrick; Heshka, Stanley; Albu, Jeanine; Heymsfield, Steven B; Goodpaster, Bret H; Visser, Marjolein; Harris, Tamara B

    BACKGROUND: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. OBJECTIVE: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and

  11. Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity.

    Directory of Open Access Journals (Sweden)

    Tal Pecht

    Full Text Available Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient.We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65 undergoing elective abdominal surgery.Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,p<0.05 and ATM lipid content (r = 0.303,p<0.05. Among patients with BMI≥25Kg/m2, linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, particularly in men.Collectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs.

  12. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume

    Directory of Open Access Journals (Sweden)

    Sanders Prashanthan

    2009-05-01

    Full Text Available Abstract Background Pericardial adipose tissue (PAT has been shown to be an independent predictor of coronary artery disease. To date its assessment has been restricted to the use of surrogate echocardiographic indices such as measurement of epicardial fat thickness over the right ventricular free wall, which have limitations. Cardiovascular magnetic resonance (CMR offers the potential to non-invasively assess total PAT, however like other imaging modalities, CMR has not yet been validated for this purpose. Thus, we sought to describe a novel technique for assessing total PAT with validation in an ovine model. Methods 11 merino sheep were studied. A standard clinical series of ventricular short axis CMR images (1.5T Siemens Sonata were obtained during mechanical ventilation breath-holds. Beginning at the mitral annulus, consecutive end-diastolic ventricular images were used to determine the area and volume of epicardial, paracardial and pericardial adipose tissue. In addition adipose thickness was measured at the right ventricular free wall. Following euthanasia, the paracardial adipose tissue was removed from the ventricle and weighed to allow comparison with corresponding CMR measurements. Results There was a strong correlation between CMR-derived paracardial adipose tissue volume and ex vivo paracardial mass (R2 = 0.89, p ex vivo paracardial mass (R2 = 0.003, p = 0.878. Conclusion In this ovine model, CMR-derived paracardial adipose tissue volume, but not the corresponding and conventional measure of paracardial adipose thickness over the RV free wall, accurately reflected paracardial adipose tissue mass. This study validates for the first time, the use of clinically utilised CMR sequences for the accurate and reproducible assessment of pericardial adiposity. Furthermore this non-invasive modality does not use ionising radiation and therefore is ideally suited for future studies of PAT and its role in cardiovascular risk prediction and

  13. Fish oil-derived long-chain n-3 polyunsaturated fatty acids reduce expression of M1-associated macrophage markers in an ex vivo adipose tissue culture model, in part through adiponectin

    OpenAIRE

    Anna A. De Boer; Jennifer M. Monk; Jennifer M. Monk; Danyelle M. Liddle; Krista A. Power; David W.L. Ma; Lindsay E. Robinson

    2015-01-01

    Adipose tissue (AT) macrophages (ATM) play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad), may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an es...

  14. 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

  15. 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.

  16. Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients.

    Science.gov (United States)

    Goossens, Chloë; Vander Perre, Sarah; Van den Berghe, Greet; Langouche, Lies

    2017-12-01

    In prolonged non-obese critically ill patients, preservation of adipose tissue is prioritized over that of the skeletal muscle and coincides with increased adipogenesis. However, we recently demonstrated that in obese critically ill mice, this priority was switched. In the obese, the use of abundantly available adipose tissue-derived energy substrates was preferred and counteracted muscle wasting. These observations suggest that different processes are ongoing in adipose tissue of lean vs. overweight/obese critically ill patients. We hypothesize that to preserve adipose tissue mass during critical illness, adipogenesis is increased in prolonged lean critically ill patients, but not in overweight/obese critically ill patients, who enter the ICU with excess adipose tissue. To test this, we studied markers of adipogenesis in subcutaneous and visceral biopsies of matched lean (n = 24) and overweight/obese (n = 24) prolonged critically ill patients. Secondly, to further unravel the underlying mechanism of critical illness-induced adipogenesis, local production of eicosanoid PPARγ agonists was explored, as well as the adipogenic potential of serum from matched lean (n = 20) and overweight/obese (n = 20) critically ill patients. The number of small adipocytes, PPARγ protein, and CEBPB expression were equally upregulated (p ≤ 0.05) in subcutaneous and visceral adipose tissue biopsies of lean and overweight/obese prolonged critically ill patients. Gene expression of key enzymes involved in eicosanoid production was reduced (COX1, HPGDS, LPGDS, ALOX15, all p ≤ 0.05) or unaltered (COX2, ALOX5) during critical illness, irrespective of obesity. Gene expression of PLA2G2A and ALOX15B was upregulated in lean and overweight/obese patients (p ≤ 0.05), whereas their end products, the PPARγ-activating metabolites 15s-HETE and 9-HODE, were not increased in the adipose tissue. In vitro, serum of lean and overweight/obese prolonged critically ill

  17. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Directory of Open Access Journals (Sweden)

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  18. Brown adipose tissue in cetacean blubber.

    Directory of Open Access Journals (Sweden)

    Osamu Hashimoto

    Full Text Available Brown adipose tissue (BAT plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1, within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool

  19. Brown adipose tissue in cetacean blubber.

    Science.gov (United States)

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  20. Regulation of glucose utilization and lipogenesis in adipose tissue ...

    Indian Academy of Sciences (India)

    ... in adipose tissue of control and diabetic animals of different ages are presented together with the effect of manganese on adipose tissue from high fat milk diet fed animals ... Hormone and Drug Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India; Molecular Medicine Unit, ...

  1. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol,

  2. A hot interaction between immune cells and adipose tissue

    NARCIS (Netherlands)

    van den Berg, S.M.

    2017-01-01

    Systemic as well as adipose tissue inflammation contributes to the development of obesity-associated diseases. This thesis describes three targets to battle this chronic inflammation in a model of diet-induced obesity in mice. First, we studied inflammation in obese white - and brown adipose tissue

  3. Mechanisms of inflammatory responses in obese adipose tissue

    NARCIS (Netherlands)

    Sun, S.Y.; Yewei, Ji; Kersten, A.H.; Qi, L.

    2012-01-01

    The fields of immunology and metabolism are rapidly converging on adipose tissue. During obesity, many immune cells infiltrate or populate in adipose tissue and promote a low-grade chronic inflammation. Studies to date have suggested that perturbation of inflammation is critically linked to nutrient

  4. Microarray analysis of adipose tissue gene expression profiles ...

    Indian Academy of Sciences (India)

    Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by the broiler industry nowadays. In order to visualize the mechanisms involved in the gene expression and regulation of lipid metabolism in adipose tissue, cDNA microarray containing 9 024 cDNA was used to construct gene ...

  5. Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty.

    Science.gov (United States)

    Stout, Michael B; Justice, Jamie N; Nicklas, Barbara J; Kirkland, James L

    2017-01-01

    Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

  6. Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology.

    Science.gov (United States)

    Louveau, I; Perruchot, M-H; Bonnet, M; Gondret, F

    2016-11-01

    Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.

  7. Maternal nutrition induces gene expression changes in fetal muscle and adipose tissues in sheep.

    Science.gov (United States)

    Peñagaricano, Francisco; Wang, Xin; Rosa, Guilherme Jm; Radunz, Amy E; Khatib, Hasan

    2014-11-28

    Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep. Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR ≤0.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR ≤0.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR ≤0.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes. These findings provide evidence that maternal nutrition during pregnancy can alter the programming of fetal muscle and fat tissues in sheep. The ramifications of the observed gene expression changes, in terms of postnatal growth, body composition, and meat quality of the offspring, warrant future investigation.

  8. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  9. Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

    Directory of Open Access Journals (Sweden)

    Craig Porter

    2013-01-01

    Full Text Available The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies.

  10. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  11. Innate immunity orchestrates adipose tissue homeostasis.

    Science.gov (United States)

    Lin, Yi-Wei; Wei, Li-Na

    2017-06-23

    Obesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

  12. Activation of brown adipose tissue in hypothyroidism.

    Science.gov (United States)

    Lapa, Constantin; Maya, Yoshifumi; Wagner, Martin; Arias-Loza, Paula; Werner, Rudolf A; Herrmann, Ken; Higuchi, Takahiro

    2015-01-01

    Brown adipose tissue (BAT) attracts growing interest as a potential therapeutic target for obesity and diabetes. Hyperthyroidism is well-known to increase BAT activity, but the role of hypothyroidism is controversial. We aimed to investigate the association between different thyroid hormone (TH) states and BAT activity. FDG-PET studies were retrospectively evaluated in thyroid cancer patients after total thyroidectomy both at euthyroidism during TH replacement or at hypothyroidism after TH cessation. Serum TH levels were compared between patients with active BAT and control patients with non-active BAT matched for age, gender, and body mass index. Additionally, animal experiments with controls (n = 5) and hypothyroid rats (n = 5) were performed. Out of 124 patients, 6 patients with active BAT were identified. These patients showed significantly higher thyroid-stimulating hormone (TSH) levels than matched controls (P hypothyroid animals showed BAT activation at room temperature (24 °C), whereas controls did not (P hypothyroidism, which might be the result of a feedback mechanism to maintain body temperature in a state of reduced basal thermogenesis. Future research needs to explore the underlying mechanistic and biological implications.

  13. New concepts in white adipose tissue physiology

    International Nuclear Information System (INIS)

    Proença, A.R.G.; Sertié, R.A.L.; Oliveira, A.C.; Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B.

    2014-01-01

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT

  14. New concepts in white adipose tissue physiology

    Energy Technology Data Exchange (ETDEWEB)

    Proença, A.R.G. [Universidade Estadual de Campinas, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Limeira, SP, Brasil, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP (Brazil); Sertié, R.A.L. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Oliveira, A.C. [Universidade Estadual do Ceará, Instituto Superior de Ciências Biomédicas, Fortaleza, CE, Brasil, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE (Brazil); Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-03-03

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

  15. Cryolipolysis for reduction of excess adipose tissue.

    Science.gov (United States)

    Nelson, Andrew A; Wasserman, Daniel; Avram, Mathew M

    2009-12-01

    Controlled cold exposure has long been reported to be a cause of panniculitis in cases such as popsicle panniculitis. Cryolipolysis is a new technology that uses cold exposure, or energy extraction, to result in localized panniculitis and modulation of fat. Presently, the Zeltiq cryolipolysis device is FDA cleared for skin cooling, as well as various other indications, but not for lipolysis. There is, however, a pending premarket notification for noninvasive fat layer reduction. Initial animal and human studies have demonstrated significant reductions in the superficial fat layer thickness, ranging from 20% to 80%, following a single cryolipolysis treatment. The decrease in fat thickness occurs gradually over the first 3 months following treatment, and is most pronounced in patients with limited, discrete fat bulges. Erythema of the skin, bruising, and temporary numbness at the treatment site are commonly observed following treatment with the device, though these effects largely resolve in approximately 1 week. To date, there have been no reports of scarring, ulceration, or alterations in blood lipid or liver function profiles. Cryolipolysis is a new, noninvasive treatment option that may be of benefit in the treatment of excess adipose tissue.

  16. Interactions between adipose tissue and the immune system in health and malnutrition.

    Science.gov (United States)

    Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Polić, Bojan

    2015-09-01

    Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Assessment of in situ adipose tissue inflammation by microdialysis

    DEFF Research Database (Denmark)

    Langkilde, Anne; Andersen, Ove; Henriksen, Jens H

    2015-01-01

    Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore...

  18. Adipose tissue, the skeleton and cardiovascular disease

    International Nuclear Information System (INIS)

    Wiklund, Peder

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western World, although the incidence of myocardial infarction (MI) has declined over the last decades. However, obesity, which is one of the most important risk factors for CVD, is increasingly common. Osteoporosis is also on the rise because of an aging population. Based on considerable overlap in the prevalence of CVD and osteoporosis, a shared etiology has been proposed. Furthermore, the possibility of interplay between the skeleton and adipose tissue has received increasing attention the last few years with the discovery that leptin can influence bone metabolism and that osteocalcin can influence adipose tissue. A main aim of this thesis was to investigate the effects of fat mass distribution and bone mineral density on the risk of MI. Using dual-energy x-ray absorptiometry (DEXA) we measured 592 men and women for regional fat mass in study I. In study II this was expanded to include 3258 men and women. In study III 6872 men and women had their bone mineral density measured in the total hip and femoral neck using DEXA. We found that a fat mass distribution with a higher proportion of abdominal fat mass was associated with both an adverse risk factor profile and an increased risk of MI. In contrast, a higher gynoid fat mass distribution was associated with a more favorable risk factor profile and a decreased risk of MI, highlighting the different properties of abdominal and gynoid fat depots (study I-II). In study III, we investigated the association of bone mineral density and risk factors shared between CVD and osteoporosis, and risk of MI. We found that lower bone mineral density was associated with hypertension, and also tended to be associated to other CVD risk factors. Low bone mineral density was associated with an increased risk of MI in both men and women, apparently independently of the risk factors studied (study III). In study IV, we investigated 50 healthy, young men to determine if

  19. Adipose tissue, the skeleton and cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Wiklund, Peder

    2011-07-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western World, although the incidence of myocardial infarction (MI) has declined over the last decades. However, obesity, which is one of the most important risk factors for CVD, is increasingly common. Osteoporosis is also on the rise because of an aging population. Based on considerable overlap in the prevalence of CVD and osteoporosis, a shared etiology has been proposed. Furthermore, the possibility of interplay between the skeleton and adipose tissue has received increasing attention the last few years with the discovery that leptin can influence bone metabolism and that osteocalcin can influence adipose tissue. A main aim of this thesis was to investigate the effects of fat mass distribution and bone mineral density on the risk of MI. Using dual-energy x-ray absorptiometry (DEXA) we measured 592 men and women for regional fat mass in study I. In study II this was expanded to include 3258 men and women. In study III 6872 men and women had their bone mineral density measured in the total hip and femoral neck using DEXA. We found that a fat mass distribution with a higher proportion of abdominal fat mass was associated with both an adverse risk factor profile and an increased risk of MI. In contrast, a higher gynoid fat mass distribution was associated with a more favorable risk factor profile and a decreased risk of MI, highlighting the different properties of abdominal and gynoid fat depots (study I-II). In study III, we investigated the association of bone mineral density and risk factors shared between CVD and osteoporosis, and risk of MI. We found that lower bone mineral density was associated with hypertension, and also tended to be associated to other CVD risk factors. Low bone mineral density was associated with an increased risk of MI in both men and women, apparently independently of the risk factors studied (study III). In study IV, we investigated 50 healthy, young men to determine if

  20. Omental adipose tissue fibrosis and insulin resistance in severe obesity

    OpenAIRE

    Guglielmi, V; Cardellini, M; Cinti, F; Corgosinho, F; Cardolini, I; D'Adamo, M; Zingaretti, M C; Bellia, A; Lauro, D; Gentileschi, P; Federici, M; Cinti, S; Sbraccia, P

    2015-01-01

    Background/Objectives: The unresolved chronic inflammation of white adipose tissue (WAT) in obesity leads to interstitial deposition of fibrogenic proteins as reparative process. The contribution of omental adipose tissue (oWAT) fibrosis to obesity-related complications remains controversial. The aim of our study was to investigate whether oWAT fibrosis may be related to insulin resistance in severely obese population. Subjects/Methods: Forty obese subjects were studied by glucose clamp befor...

  1. 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...

  2. Central control of brown adipose tissue thermogenesis

    Directory of Open Access Journals (Sweden)

    Shaun F. Morrison

    2012-01-01

    Full Text Available Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. Mitochondrial oxidation in brown adipose tissue (BAT is a significant source of neurally-regulated metabolic heat production in many species from mouse to man. BAT thermogenesis is regulated by neural networks in the central nervous system which responds to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate BAT sympathetic nerve activity. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates BAT thermogenesis and includes the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature during fever. The cold thermal afferent circuit from cutaneous thermal receptors, through second-order thermosensory neurons in the dorsal horn of the spinal cord ascends to activate neurons in the lateral parabrachial nucleus which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of BAT thermogenesis-promoting neurons in the dorsomedial hypothalamus activates BAT sympathetic premotor neurons in the rostral ventromedial medulla, including the rostral raphe pallidus, which provide excitatory, and possibly disinhibitory, inputs to spinal sympathetic circuits to drive BAT thermogenesis. Other recently recognized central sites influencing BAT thermogenesis and energy expenditure are also described.

  3. Visceral adipose tissue quantification using Lunar Prodigy.

    Science.gov (United States)

    Ergun, David L; Rothney, Megan P; Oates, Mary K; Xia, Yi; Wacker, Wynn K; Binkley, Neil C

    2013-01-01

    A dual-energy X-ray absorptiometry (DXA) application to measure visceral adipose tissue (VAT) in the android region of a total body DXA scan has recently been developed. This new application, CoreScan, has been validated on the Lunar iDXA (GE Healthcare, Madison, WI) densitometer against volumetric computed tomography. The geometric assumptions underlying the CoreScan model are the same on the Prodigy (GE Healthcare, Madison, WI) densitometer. However, differences between the peak X-ray voltage and detector array configurations may lead to differences in VAT quantification. The purpose of this study was to evaluate the agreement of Prodigy and iDXA CoreScan values and to characterize differences in VAT precision between the instruments. Data from volunteers with paired Prodigy and iDXA measurements were used to define empirical adjustments to the VAT algorithm parameters (n=59) and validate performance on Prodigy (n=62). Prodigy VAT measurements were highly correlated to iDXA (r=0.984). The mean of the Prodigy-iDXA VAT volume differences was -13.8cm³ with a 95% confidence interval of -45 to +17cm³. The Bland-Altman 95% limits of agreement for the 2 methods were -252 to +224cm³. Measurement of short-term precision showed that measurement error variance on iDXA was smaller (pProdigy (coefficient of variance: 7.3% vs 9.8%). Precision results are in agreement with previous reports on the differences between Prodigy and iDXA for body composition measures. Prodigy and iDXA measures of VAT are similar, but the lower precision of the Prodigy may require investigators to target larger changes in VAT. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  4. Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue.

    Science.gov (United States)

    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.

  5. Metabolic syndrome pathophysiology: the role of adipose tissue.

    Science.gov (United States)

    Laclaustra, Martin; Corella, Dolores; Ordovas, José M

    2007-02-01

    Several pathophysiological explanations for the metabolic syndrome have been proposed involving insulin resistance, chronic inflammation and ectopic fat accumulation following adipose tissue saturation. However, current concepts create several paradoxes, including limited cardiovascular risk reduction with intensive glucose control in diabetics, therapies that result in weight gain (PPAR agonists), and presence of some of the metabolic traits among some lipodystrophies. We propose the functional failure of an organ, in this case, the adipose tissue as a model to interpret its manifestations and to reconcile some of the apparent paradox. A cornerstone of this model is the failure of the adipose tissue to buffer postprandial lipids. In addition, homeostatic feedback loops guide physiological and pathological adipose tissue activities. Fat turnover is determined by a complex equilibrium in which insulin is a main factor but not the only one. Chronically inadequate energy balance may be a key factor, stressing the system. In this situation, an adipose tissue functional failure occurs resulting in changes in systemic energy delivery, impaired glucose consumption and activation of self-regulatory mechanisms that extend their influence to whole body homeostasis system. These include changes in adipokines secretion and vascular effects. The functional capacity of the adipose tissue varies among subjects explaining the incomplete overlapping among the metabolic syndrome and obesity. Variations at multiple gene loci will be partially responsible for these interindividual differences. Two of those candidate genes, the adiponectin (APM1) and the perilipin (PLIN) genes, are discussed in more detail.

  6. Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment

    Directory of Open Access Journals (Sweden)

    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.

  7. The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue.

    Science.gov (United States)

    He, Yunfan; Dong, Ziqing; Xie, Gan; Zhou, Tao; Lu, Feng

    2017-04-01

    Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.

  8. Brown adipose tissue in morbidly obese subjects.

    Directory of Open Access Journals (Sweden)

    Guy H E J Vijgen

    Full Text Available BACKGROUND: Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI and body fat percentage (BF%, suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. METHODS AND FINDINGS: After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT. Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39 from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001, respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001 and BF% (r = 0.75; P<0.001. Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26 mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001, and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001, indicating a role for BAT in CIT in humans. CONCLUSIONS: This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid obesity.

  9. Exercise Regulation of Marrow Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Gabriel M Pagnotti

    2016-07-01

    Full Text Available Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally-supportive tissues, inhibits bone resorption and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot, or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a 5-fold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  10. Adipose tissue as mesenchymal stem cells source in equine tendinitis treatment

    Directory of Open Access Journals (Sweden)

    Armando de Mattos Carvalho

    2016-12-01

    Full Text Available Tendinitis is an important high-relapse-rate disease, which compromises equine performance and may result in early athletic life end to affected animals. Many therapies have been set to treat equine tendinitis; however, just few result in improved relapse rates, quality of extracellular matrix (ECM and increased biomechanical resistance of the treated tissue. Due to advances in the regenerative medicine, promising results were initially obtained through the implantation of mesenchymal stem cells (MSC derived from the bone marrow in the equine tendon injury. Since then, many studies have been using MSCs from different sources for therapeutic means in equine. The adipose tissue has appeared as feasible MSC source. There are promising results involving equine tendinitis therapy using mesenchymal stem cells from adipose tissue (AdMSCs.

  11. Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues.

    Science.gov (United States)

    Contreras, G Andres; Strieder-Barboza, Clarissa; de Souza, Jonas; Gandy, Jeff; Mavangira, Vengai; Lock, Adam L; Sordillo, Lorraine M

    2017-01-01

    The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis. However, the effect of lipolysis intensity during the transition from gestation to lactation on fatty acid substrate availability and subsequent AT oxylipid biosynthesis is currently unknown. We hypothesized that in periparturient dairy cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide with changes in lipolysis intensity and stage of lactation. Blood and subcutaneous AT samples were collected from periparturient cows at -27±7 (G1) and -10±5 (G2) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA concentrations increased as parturition approached and were highest at PP. Cows exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L) had higher body condition scores at G1 compared to cows with low lipolysis rate (FFAoxylipids including 5- and 15-HETE and 13-HODE. These results support a role for certain linoleic and arachidonic acid-derived oxylipids as positive and negative modulators of AT inflammation during periparturient lipolysis.

  12. Epicardial Adipose Tissue Thickness and Ablation Outcome of Atrial Fibrillation

    Science.gov (United States)

    Tsao, Hsuan-Ming; Lin, Yenn-Jiang; Yun, Chun-Ho; Lai, Yau-Huei; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chang, Hung-Yu; Kuo, Jen-Yuan; Yeh, Hung-I; Wu, Tsu-Juey; Hsieh, Ming-Hsiung; Yu, Wen-Chung; Chen, Shih-Ann

    2013-01-01

    Objectives Epicardial fat was closely related to atrial fibrillation (AF). Transthoracic echocardiography (TTE) has been proposed to be a convenient imaging tool in assessing epicardial adipose tissue (EAT). The goal of the present study was to investigate whether the EAT thickness measured on TTE was a useful parameter in predicting procedural outcomes of AF ablations. Methods and Results A total of 227 paroxysmal AF (PAF) and 56 non-paroxysmal AF (non-PAF) patients receiving catheter ablations from 2008-2010 were enrolled. Echocardiography-derived regional EAT thickness from parasternal long-axis view was quantified for each patient. Free of recurrence was defined as the absence of atrial arrhythmias without using antiarrhythmic agents after ablations. The mean EAT thickness of the study population was 6.1 ± 0.8 mm. Non-PAF patients had a thicker EAT than that of PAF patients (7.0 ± 0.7 mm versus 5.9 ± 0.7 mm, p value EAT thickness were independent predictors of recurrence after catheter ablations. At a cutoff value of 6 mm for PAF and 6.9 mm for non-PAF, the measurement of EAT thickness could help us to identify patients at risk of recurrences. Conclusions EAT thickness may serve as a useful parameter in predicting recurrences after AF ablations. Compared to other imaging modalities, TTE can be an alternative choice with less cost and time in assessing the effects of EAT on ablation outcomes. PMID:24066158

  13. β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Darimont Christian

    2004-08-01

    Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

  14. Local androgen inactivation in abdominal visceral adipose tissue.

    Science.gov (United States)

    Blouin, Karine; Richard, Christian; Bélanger, Chantal; Dupont, Pierre; Daris, Marleen; Laberge, Philippe; Luu-The, Van; Tchernof, André

    2003-12-01

    We examined the expression and activity of two enzymes from the aldoketoreductase (AKR) family 1C, namely type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD-5, AKR1C3) and type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD-3, AKR1C2) in female sc and omental adipose tissue and in preadipocyte primary cultures. 17beta-HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor androstenedione, whereas 3alpha-HSD-3 inactivates dihydrotestosterone. mRNAs of both enzymes were detected in adipose tissue from the omental and sc compartments. Real-time PCR quantification indicated a 3-fold higher 3alpha-HSD-3 expression compared with 17beta-HSD-5, and the expression of both enzymes tended to be higher in the sc vs. the omental depot. Accordingly, dose-response and time-course experiments performed in preadipocyte primary cultures indicated that 3alpha-HSD activity was higher than 17beta-HSD activity (13-fold maximum velocity difference). We measured 3alpha-HSD activity in omental and sc adipose tissue samples of 32 women for whom body composition and body fat distribution were evaluated by dual-energy x-ray absorptiometry and CT, respectively. We found that androgen inactivation in omental adipose tissue through 3alpha-HSD activity was significantly higher in women with elevated vs. low visceral adipose tissue accumulation (1.7-fold difference; P < 0.05). Moreover, omental adipose tissue 3alpha-HSD activity was positively and significantly associated with CT-measured visceral adipose tissue (r = 0.43; P < 0.02) and omental adipocyte diameter (r = 0.42; P < 0.02). These results indicate that local androgen inactivation is a predominant reaction in female abdominal adipose tissue, with the greatest conversion rates observed in the presence of abdominal visceral obesity. Increased androgen inactivation in omental adipose tissue of abdominally obese women may impact locally on the regulation of adipocyte metabolism.

  15. Factors affecting adipose tissue development in chickens: A review.

    Science.gov (United States)

    Wang, Guoqing; Kim, Woo Kyun; Cline, Mark A; Gilbert, Elizabeth R

    2017-10-01

    The intense genetic selection for rapid growth in broilers has resulted in an increase in voluntary feed intake and growth rate, accompanied by increased fat deposition in adipose tissue depots throughout the body. Adipose tissue expansion is a result of the formation of adipocytes (several processes collectively referred to as adipogenesis) and cellular accumulation of triacylglycerols inside lipid droplets. In mammals, different anatomical depots are metabolically distinct. The molecular and cellular mechanisms underlying adipose tissue development have been characterized in mammalian models, whereas information in avian species is scarce. The purpose of this review is to describe factors regulating adipogenesis in chickens, with an emphasis on dietary factors and the broiler. Results from many studies have demonstrated effects of dietary nutrient composition on adipose tissue development and lipid metabolism. Transcription factors, such as peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding proteins α and β, and sterol regulatory element binding proteins orchestrate a series of cellular events that lead to an increase in activity of fatty acid transport proteins and enzymes that are responsible for triacylglycerol synthesis. Understanding the mechanisms underlying adipose tissue development may provide a practical strategy to affect body composition of the commercial broiler while providing insights on diets that maximize conversion into muscle rather than fat and affect depot-dependent deposition of lipids. Because of the propensity to overeat and become obese, the broiler chicken also represents an attractive biomedical model for eating disorders and obesity in humans. © 2017 Poultry Science Association Inc.

  16. Ghrelin receptor regulates adipose tissue inflammation in aging.

    Science.gov (United States)

    Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

  17. Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

    Science.gov (United States)

    Santosa, Sylvia; Bush, Nikki C; Jensen, Michael D

    2017-08-01

    Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. This was a prospective, randomized trial. Mayo Clinic Clinical Research Unit. Thirty-two male volunteers ages 18 to 50 participated in these studies. Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group. We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content. Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity. These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.

  18. Ghrelin receptor regulates adipose tissue inflammation in aging

    Science.gov (United States)

    Buras, Eric D.; Yu, Kaijiang; Wang, Ruitao; Smith, C. Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr−/− mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr−/− mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsr−/− mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID:26837433

  19. Increased Ratio of Visceral to Subcutaneous Adipose Tissue in Septic Patients Is Associated With Adverse Outcome.

    Science.gov (United States)

    Pisitsak, Chawika; Lee, Joseph G H; Boyd, John H; Coxson, Harvey O; Russell, James A; Walley, Keith R

    2016-11-01

    Visceral and subcutaneous adipose tissue may contribute differentially to the septic inflammatory response. Accordingly, we tested the hypothesis that the ratio of visceral to subcutaneous adipose tissue is associated with altered sepsis outcome. A retrospective analysis from a cohort of sepsis patients admitted between 2004 and 2009. A mixed medical-surgical ICU at St. Paul's Hospital in Vancouver, Canada. Patients older than 16 years old who had sepsis and underwent abdominal CT scan (n = 257) for clinical reasons. None. We measured the visceral adipose tissue and subcutaneous adipose tissue areas and calculated the visceral adipose tissue-to-subcutaneous adipose tissue ratio. Visceral adipose tissue/subcutaneous adipose tissue was not correlated with body mass index (r = -0.015, p = NS) and therefore provides additional unique information independent of body mass index. Sepsis patients with higher visceral adipose tissue/subcutaneous adipose tissue had greater 90-day mortality than patients with lower visceral adipose tissue/subcutaneous adipose tissue (log-rank test, linear-by linear association p ratios of 2.01 (95% CI, 1.01-3.99) for the third visceral adipose tissue/subcutaneous adipose tissue quartile compared with the first quartile and 2.32 (95% CI, 1.15-4.69) for the highest visceral adipose tissue/subcutaneous adipose tissue quartile when compared with the first quartile. Increased mortality for patients with higher visceral adipose tissue/subcutaneous adipose tissue was found for both patients with body mass index less than 25 kg/m (p = 0.004) and for body mass index greater than or equal to 25 kg/m (p = 0.023). Furthermore, we found significantly greater need for mechanical ventilation, renal replacement therapy, and ICU stay in patients in the highest visceral adipose tissue/subcutaneous adipose tissue quartile. The ratio of proinflammatory (interleukin-8) to anti-inflammatory (interleukin-10) plasma cytokine levels was greater in patients with

  20. Growth hormone and adipose tissue: beyond the adipocyte.

    Science.gov (United States)

    Berryman, Darlene E; List, Edward O; Sackmann-Sala, Lucila; Lubbers, Ellen; Munn, Rachel; Kopchick, John J

    2011-06-01

    The last two decades have seen resurgence in research focused on adipose tissue. In part, the enhanced interest stems from an alarming increase in obesity rates worldwide. However, an understanding that this once simple tissue is significantly more intricate and interactive than previously realized has fostered additional attention. While few would argue that growth hormone (GH) radically alters fat mass, newer findings revealing the complexity of adipose tissue requires that GH's influence on this tissue be reexamined. Therefore, the objective of this review is to describe the more recent understanding of adipose tissue and to summarize our current knowledge of how GH may influence and contribute to these newer complexities of this tissue with special focus on the available data from mice with altered GH action. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Biomarkers of Habitual Fish Intake in Adipose-Tissue

    DEFF Research Database (Denmark)

    Marckmann, P.; Lassen, Anne Dahl; Haraldsdottir, H.

    1995-01-01

    /d) was significantly associated with adipose tissue docosahexaenoic acid content (DHA; r = 0.55 and 0.58, respectively, P eicosapentaenoic and docosapentaenoic acid contents. Our study indicates that the adipose tissue DHA content is the biomarker of choice for the assessment of long......The association between habitual fish and marine n-3 polyunsaturated fatty acid (PUFA) intake, and the fatty acid composition of subcutaneous fat was studied in 24 healthy young volunteers. Habitual dietary intakes were estimated from three 7-d weighed food records made at months 0, 5, and 8...... of the 8-mo study period. The adipose tissue fatty acid composition of each individual was determined by gas chromatography as the mean of two gluteal biopsies, obtained in the first and the last month of the study. The daily consumption of fish and of marine n-3 PUFAs in absolute terms (g...

  2. The effect of hypokinesia on lipid metabolism in adipose tissue

    Science.gov (United States)

    Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

    The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

  3. The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Silva Meirelles, Lindolfo da, E-mail: lindolfomeirelles@gmail.com [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Laboratory for Stem Cells and Tissue Engineering, PPGBioSaúde, Lutheran University of Brazil, Av. Farroupilha 8001, 92425-900 Canoas, RS (Brazil); Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre [Laboratory of Large-Scale Functional Biology (LLSFBio), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); and others

    2016-12-10

    Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

  4. Defective regulation of adipose tissue autophagy in obesity.

    Science.gov (United States)

    Nuñez, C E; Rodrigues, V S; Gomes, F S; Moura, R F de; Victorio, S C; Bombassaro, B; Chaim, E A; Pareja, J C; Geloneze, B; Velloso, L A; Araujo, E P

    2013-11-01

    Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. Adipose tissue autophagy was evaluated in mice and humans. First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.

  5. The influence of retrobulbar adipose tissue volume upon intraocular pressure in obesity

    Directory of Open Access Journals (Sweden)

    Stojanov Oliver

    2013-01-01

    Full Text Available Background/Aim. It is known that glaucoma is associated with elevated intraocular pressure and obesity, yet the precise etiology remains unclear. The aim of this study was to determine whether there is a potential causality between the volume of retrobulbar adipose tissue and the level of intraocular pressure in obese subjects compared with non-obese. Methods. A total of 100 subjects were divided according to the body mass index (BMI, into two groups: normal weight (n = 50, BMI = 18-24.9 kg/m2 and obese (n = 50, BMI ≥ 30 kg/m2 subjects. Anthropometric measurements, body composition analysis, measurement of intraocular pressure, as well as magnetic resonance imaging (MRI of the head at the level of the optic nerve, and the derived retrobulbar adipose tissue volume, were undertaken in all subjects. Results. The obese subjects, as compared with normal weight ones, had a significantly higher mean retrobulbar adipose tissue volume (6.23 cm3 vs 4.85 cm3, p < 0.01 and intraocular pressure (15.96 mmHg vs 12.99 mmHg, p < 0.01. Furthermore, intraocular pressure correlated positively with retrobulbar adipose tissue volume. Conclusion. In obese people, elevated intraocular pressure may be caused by changes in ocular blood flow, affected by the physical pressure exerted by higher retrobulbar adiposity, and/or by internal vascular changes secondary to complications of obesity. These findings indicate the need for more frequent measurement of intraocular pressure in obese individuals to earlier detect glaucoma, and in so doing prevent irreversible blindness.

  6. Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Ma, Shuai; Li, Fen; Yuan, Miao; Xu, Huibi; Huang, Kaixun

    2015-11-27

    Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.

  7. Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

    International Nuclear Information System (INIS)

    Zhou, Jun; Xu, Gang; Ma, Shuai; Li, Fen; Yuan, Miao; Xu, Huibi; Huang, Kaixun

    2015-01-01

    Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.

  8. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

    2011-01-01

    in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate......Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...

  9. Visceral adipose tissue area measurement at a single level: can it represent visceral adipose tissue volume?

    Science.gov (United States)

    Noumura, Yusuke; Kamishima, Tamotsu; Sutherland, Kenneth; Nishimura, Hideho

    2017-08-01

    Measurement of visceral adipose tissue (VAT) needs to be accurate and sensitive to change for risk monitoring. The purpose of this study is to determine the CT slice location where VAT area can best reflect changes in VAT volume and body weight. 60 plain abdominal CT images from 30 males [mean age (range) 51 (41-68) years, mean body weight (range) 71.1 (101.9-50.9) kg] who underwent workplace screenings twice within a 1-year interval were evaluated. Automatically calculated and manually corrected areas of the VAT of various scan levels using "freeform curve" region of interest on CT were recorded and compared with body weight changes. The strongest correlations of VAT area with VAT volume and body weight changes were shown in a slice 3 cm above the lower margin of L3 with r values of 0.853 and 0.902, respectively. VAT area measurement at a single level 3 cm above the lower margin of the L3 vertebra is feasible and can reflect changes in VAT volume and body weight. Advances in knowledge: As VAT area at a CT slice 3cm above the lower margin of L3 can best reflect interval changes in VAT volume and body weight, VAT area measurement should be selected at this location.

  10. The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes.

    Science.gov (United States)

    Tobin, L; Simonsen, L; Bülow, J

    2011-11-01

    Postprandially, the blood flow and uptake of non-esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin-resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age- and weight-matched healthy subjects were studied. Contrast-enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75-g oral glucose load. Abdominal subcutaneous ATBF was measured using (133) Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  11. Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Madsen, J

    1994-01-01

    A technique for catheterization of a vein draining abdominal subcutaneous tissue and a microdialysis technique that allows measurements of intercellular water concentrations in adipose tissue in humans have recently been described. In the present study, we compare the two techniques during an oral...... agreement between the concentrations obtained by the two techniques with respect to glucose and glycerol, whereas lactate concentrations are very different. With regard to substrate fluxes calculated by Fick's principle, the catheterization technique is probably the most reliable, considering the numerous...

  12. Microarray analysis of adipose tissue gene expression profiles ...

    Indian Academy of Sciences (India)

    MADU

    and provides a major protein source from meat and eggs throughout the world. Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by ..... important role in cholesterol homeostasis (Bhattacharyya et al 1993). Cholesterol is removed from peripheral tissues and transported either directly ...

  13. Limitations of ractopamine to affect adipose tissue metabolism in swine.

    Science.gov (United States)

    Liu, C Y; Grant, A L; Kim, K H; Ji, S Q; Hancock, D L; Anderson, D B; Mills, S E

    1994-01-01

    To determine the temporal effect of ractopamine (Rac), a phenethanolamine, on adipose lipogenic enzyme activity and gene expression, 20 crossbred barrows were fed Rac (20 mg/kg of diet) for 0, 1, 8, or 24 d before slaughter (105 +/- 1 kg). Ractopamine had no effect (P > .05) on the activity of acetyl-coenzyme A carboxylase or malic enzyme in either the middle or outer layers of subcutaneous adipose tissue. Similarly, mRNA abundance for acetyl-coenzyme A carboxylase and the glucose transport proteins Glut 1 and Glut 4 were not affected by Rac in either adipose depot. Despite the inability of Rac to affect adipose tissue metabolism, Rac increased nitrogen retention, longissimus muscle area, and alpha-actin gene expression in skeletal muscle. Results indicate that Rac was not a functional beta-adrenergic agonist toward adipose tissue in this study. We suggest that the response to Rac in adipose tissue is masked by a combination of factors including tissue insensitivity, Rac-dose limitation, inherent partial agonism of Rac, and beta-adrenoceptor down-regulation.

  14. Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content

    DEFF Research Database (Denmark)

    Morgan-Bathke, Maria; Harteneck, Debra; Jaeger, Philippa

    2017-01-01

    OBJECTIVE: The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ...

  15. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    DEFF Research Database (Denmark)

    Sun, Kai; Park, Jiyoung; Gupta, Olga T

    2014-01-01

    We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonst...

  16. Chagas disease, adipose tissue and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fnu Nagajyothi

    2009-07-01

    Full Text Available Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor ³, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

  17. 12- and 15-Lipoxygenases in Adipose Tissue Inflammation

    Science.gov (United States)

    Cole, Banumathi K.; Lieb, David C.; Dobrian, Anca D.; Nadler, Jerry L.

    2012-01-01

    The lipoxygenases (LOs) are principal enzymes involved in the oxidative metabolism of polyunsaturated fatty acids, including arachidonic acid. 12- and 15-LO and their lipid metabolites have been implicated in the development of insulin resistance and diabetes. Adipose tissue, and in particular visceral adipose tissue, plays a primary role in the development of the inflammation seen in these conditions. 12- and 15-LO and their lipid metabolites act as upstream regulators of many of the cytokines involved in the inflammatory response in adipose tissue. While the role that 12- and 15-LO play in chronically inflamed adipose tissue is becoming clearer, there are still many questions that remain unanswered regarding their activation, signaling pathways, and roles in healthy fat. 12- and 15-LO also generate products with anti-inflammatory properties that are under investigation. Therefore, 12- and 15-LO have the potential to be very important targets for therapeutics aimed at reducing insulin resistance and the comorbid conditions associated with obesity. PMID:22951339

  18. Adipose Tissue Tumours in Port Harcourt (A ten year review ...

    African Journals Online (AJOL)

    Conclusion: Adipose tissue tumors are one of the commonest soft tissue tumors. Though not given much attention in medical practice and in literature, it posed cosmetic problems. The location and size of the tumor determined the symptoms which ranges from dyspnea to a feeling of fullness and discomfort on motion.

  19. Quantification of visceral adipose tissue in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Frøssing, Signe; Nylander, Malin Chatarina; Chabanova, Elizaveta

    2018-01-01

    Background Polycystic ovary syndrome (PCOS) is associated with frequent overweight and abdominal obesity. Quantifying visceral adipose tissue (VAT) in PCOS patients can be a tool to assess metabolic risk and monitor effects of treatment. The latest dual-energy X-ray absorptiometry (DXA) technology...

  20. Regulation of glucose utilization and lipogenesis in adipose tissue ...

    Indian Academy of Sciences (India)

    Unknown

    Both insulin and manganese caused an increased oxidation of carbon-1 of glucose and an increase of its incorporation into 14C-lipids in ... of the importance of obesity to cardiovascular problems,. NIDDM and insulin resistance ... genesis in liver and adipose tissue caused by manganese treatment of rats fed a high fat diet ...

  1. Regulation of glucose utilization and lipogenesis in adipose tissue ...

    Indian Academy of Sciences (India)

    Unknown

    In order to evaluate the modulatory effects of manganese, high fat diet fed and alloxan diabetic rats were taken and the changes in the glucose oxidation, glycerol release and effects of manganese on these parameters were measured from adipose tissue. An insulin-mimetic effect of manganese was observed in the adipose ...

  2. Spice Up Your Life: Adipose Tissue and Inflammation

    Science.gov (United States)

    Agarwal, Anil K.

    2014-01-01

    Cells of the immune system are now recognized in the adipose tissue which, in obesity, produces proinflammatory chemokines and cytokines. Several herbs and spices have been in use since ancient times which possess anti-inflammatory properties. In this perspective, I discuss and propose the usage of these culinary delights for the benefit of human health. PMID:24701352

  3. Spice Up Your Life: Adipose Tissue and Inflammation

    Directory of Open Access Journals (Sweden)

    Anil K. Agarwal

    2014-01-01

    Full Text Available Cells of the immune system are now recognized in the adipose tissue which, in obesity, produces proinflammatory chemokines and cytokines. Several herbs and spices have been in use since ancient times which possess anti-inflammatory properties. In this perspective, I discuss and propose the usage of these culinary delights for the benefit of human health.

  4. Adipose tissue fatty acid patterns and changes in anthropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

    2011-01-01

    Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissu...... fatty acids and changes in anthropometry....

  5. Adipose tissue as an immunological organ : implications for childhood obesity

    NARCIS (Netherlands)

    Schipper, H.S.

    2013-01-01

    Obesity is increasingly considered as an inflammatory disorder. In adults, obesity induces inflammation of adipose tissue (AT). Through the release of inflammatory lipids and immune mediating proteins called adipokines, AT inflammation spreads to other tissues ranging from liver and muscle to the

  6. Epicardial adipose tissue in endocrine and metabolic diseases.

    Science.gov (United States)

    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  7. Vitamin D and adipose tissue - more than storage

    Directory of Open Access Journals (Sweden)

    Shivaprakash Jagalur Mutt

    2014-06-01

    Full Text Available The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OHD, no evidence was obtained for a BMI lowering effect by higher 25(OHD. Some of the physiological functions of 1,25(OH2D3 (1,25-dihydroxycholecalciferol or calcitriol via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g. in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH2D3, vitamin D binding proteins (VDBPs and nuclear vitamin D receptor (VDR after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR -/- and CYP27B1 knock out (CYP27B1 -/- mouse models: Both VDR -/- and CYP27B1 -/- models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH2D3. Experimental studies demonstrate that 1,25(OH2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases.

  8. Vitamin D and adipose tissue-more than storage.

    Science.gov (United States)

    Mutt, Shivaprakash J; Hyppönen, Elina; Saarnio, Juha; Järvelin, Marjo-Riitta; Herzig, Karl-Heinz

    2014-01-01

    The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR(-/-)) and CYP27B1 knock out (CYP27B1 (-/-)) mouse models: Both VDR(-/-) and CYP27B1(-/-) models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases.

  9. Alternative mechanism for white adipose tissue lipolysis after thermal injury.

    Science.gov (United States)

    Diao, Li; Patsouris, David; Sadri, Ali-Reza; Dai, Xiaojing; Amini-Nik, Saeid; Jeschke, Marc G

    2015-12-29

    Extensively burned patients often suffer from sepsis, a complication that enhances post-burn hypermetabolism and contributes to increased incidence of multiple organ failure, morbidity and mortality. Despite the clinical importance of burn sepsis, the molecular and cellular mechanisms of such infection-related metabolic derangements and organ dysfunction are still largely unknown. We recently found that upon endoplasmic reticulum (ER) stress, the white adipose tissue (WAT) interacts with the liver via inflammatory and metabolic signals leading to profound hepatic alterations, including hepatocyte apoptosis and hepatic fatty infiltration. We therefore hypothesized that burn plus infection causes an increase in lipolysis of WAT after major burn, partially through induction of ER stress, contributing to hyperlipidemia and profound hepatic lipid infiltration. We used a two-hit rat model of 60% total body surface area scald burn, followed by intraperitoneal injection of Pseudomonas Aeruginosa-derived lipopolysaccharide (LPS) 3 days post-burn. One day later, animals were sacrificed and liver and epididymal WAT (EWAT) samples were collected for gene expression, protein analysis and histological study of inflammasome activation, ER stress, apoptosis and lipid metabolism. Our results showed that burn plus LPS profoundly increased lipolysis in WAT associated with significantly increased hepatic lipid infiltration. Burn plus LPS augmented ER stress by upregulating CHOP and activating ATF6, inducing NLRP3 inflammasome activation and leading to increased apoptosis and lipolysis in WAT with a distinct enzymatic mechanism related to inhibition of AMPK signaling. In conclusion, burn sepsis causes profound alterations in WAT and liver which are associated with changes in organ function and structure.

  10. The influence of perivascular adipose tissue on vascular homeostasis

    Directory of Open Access Journals (Sweden)

    Szasz T

    2013-03-01

    Full Text Available Theodora Szasz,1 Gisele Facholi Bomfim,2 R Clinton Webb1 1Department of Physiology, Georgia Regents University, Augusta, USA; 2Department of Pharmacology, University of São Paulo, São Paulo, Brazil Abstract: The perivascular adipose tissue (PVAT is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT. Keywords: adipokines

  11. Articular and subcutaneous adipose tissues of rheumatoid arthritis patients represent equal sources of immunoregulatory mesenchymal stem cells.

    Science.gov (United States)

    Skalska, Urszula; Kuca-Warnawin, Ewa; Kornatka, Anna; Janicka, Iwona; Musiałowicz, Urszula; Burakowski, Tomasz; Kontny, Ewa

    2017-12-01

    Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties, but their activity is dependent on signals provided by the local microenvironment. It is likely that highly inflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) has been analysed. Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from rheumatoid arthritis (RA) patients undergoing total knee joint replacement surgery. ASCs were isolated accordingly to the routinely applied procedure, expanded and treated or not with IFNγ and TNF (10 ng/ml). To evaluate immunomodulatory properties of AT- and Sc-ASCs, co-cultures with peripheral blood mononuclear cells (PBMCs) from healthy donors have been set. Proliferation of activated PBMCs ( 3 H-thymidine incorporation method), secretion of IL-10 and IL-17A in co-culture supernatants (specific ELISA tests) and T regulatory FoxP3 + cells (Tregs) percentage have been evaluated (flow cytometry). Performed experiments demonstrated that ASCs from both sources have comparable properties. They suppress proliferation of activated PBMCs to the similar extent, induce IL-10 secretion by resting PBMCs and moderately induce generation of FoxP3 + Treg cells. Interestingly, both AT-ASCs and Sc-ASCs cause increase of IL-17A secretion by activated PBMCs as well as induce up-regulation of IL-6 concentration in co-culture supernatants. We demonstrated that AT-ASCs and Sc-ASCs obtained from RA patients possess similar immunomodulatory properties despite different localization and distinct cytokine milieu of tissue of origin. Our results indicate that ASCs derived from rheumatoid adipose tissues are not strongly immunosuppressive in vitro and that they may contribute to the pathogenesis of RA due to IL-17A

  12. Diferenciação de células-tronco mesenquimais derivadas do tecido adiposo em cardiomiócitos Differentiation of adipose tissue-derived mesenchymal stem cells into cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Pablo Herthel Carvalho

    2013-01-01

    as MSC differentiated into cardiomyocytes, has been used in the attempt to minimize the effects of ischemic-hypoxic lesions and those affecting the electrical conduction system of the heart. OBJECTIVE: The present study compared three distinct protocols for induced differentiation of MSC into cardiomyocytes aimed at finding a viable method for producing a large number of functional cells expressing cardiomyogenic phenotype. METHODS: Mesenchymal stem cells were obtained from the adipose tissue of young transgenic Lewis rats expressing green fluorescent protein (GFP, and submitted to three distinct differentiation-inducing media: 1 Planat-Bérnard, 2 5-azacytidine, and 3 Planat-Bérnard + 5-azacytidine; further, these cells were identified based on the expression of cardiac cell markers. RESULTS: All three protocols detected the expression of sarcomeric-alpha-actinin protein in the exoskeleton of cells, expression of connexin-43 in the nuclear and cytoplasmic membrane, and formation of gap junctions, which are necessary for electrical impulse propagation in the myocardium. However, no spontaneous cell contraction was observed with any of the tested protocols. CONCLUSION: Induction with 5-azacytidine provided an effective cadiomyogenic cellular differentiation similar to that obtained with Planat-Bénard media. Therefore, 5-azacytidine was the method of choice for being the simplest, fastest and lowest-cost protocol for cell differentiation.

  13. Diferenciação de células-tronco mesenquimais derivadas do tecido adiposo em cardiomiócitos Differentiation of adipose tissue-derived mesenchymal stem cells into cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Pablo Herthel Carvalho

    2012-01-01

    as MSC differentiated into cardiomyocytes, has been used in the attempt to minimize the effects of ischemic-hypoxic lesions and those affecting the electrical conduction system of the heart. OBJECTIVE: The present study compared three distinct protocols for induced differentiation of MSC into cardiomyocytes aimed at finding a viable method for producing a large number of functional cells expressing cardiomyogenic phenotype. METHODS: Mesenchymal stem cells were obtained from the adipose tissue of young transgenic Lewis rats expressing green fluorescent protein (GFP, and submitted to three distinct differentiation-inducing media: 1 Planat-Bérnard, 2 5-azacytidine, and 3 Planat-Bérnard + 5-azacytidine; further, these cells were identified based on the expression of cardiac cell markers. RESULTS: All three protocols detected the expression of sarcomeric-alpha-actinin protein in the exoskeleton of cells, expression of connexin-43 in the nuclear and cytoplasmic membrane, and formation of gap junctions, which are necessary for electrical impulse propagation in the myocardium. However, no spontaneous cell contraction was observed with any of the tested protocols. CONCLUSION: Induction with 5-azacytidine provided an effective cadiomyogenic cellular differentiation similar to that obtained with Planat-Bénard media. Therefore, 5-azacytidine was the method of choice for being the simplest, fastest and lowest-cost protocol for cell differentiation.

  14. Fructose consumption enhances glucocorticoid action in rat visceral adipose tissue.

    Science.gov (United States)

    Bursać, Biljana N; Djordjevic, Ana D; Vasiljević, Ana D; Milutinović, Danijela D Vojnović; Veličković, Nataša A; Nestorović, Nataša M; Matić, Gordana M

    2013-06-01

    The rise in consumption of refined sugars high in fructose appears to be an important factor for the development of obesity and metabolic syndrome. Fructose has been shown to be involved in genesis and progression of the syndrome through deregulation of metabolic pathways in adipose tissue. There is evidence that enhanced glucocorticoid regeneration within adipose tissue, mediated by the enzyme 11beta-hydroxysteroid dehydrogenase Type 1 (11βHSD1), may contribute to adiposity and metabolic disease. 11βHSD1 reductase activity is dependent on NADPH, a cofactor generated by hexose-6-phosphate dehydrogenase (H6PDH). We hypothesized that harmful effects of long-term high fructose consumption could be mediated by alterations in prereceptor glucocorticoid metabolism and glucocorticoid signaling in the adipose tissue of male Wistar rats. We analyzed the effects of 9-week drinking of 10% fructose solution on dyslipidemia, adipose tissue histology and both plasma and tissue corticosterone level. Prereceptor metabolism of glucocorticoids was characterized by determining 11βHSD1 and H6PDH mRNA and protein levels. Glucocorticoid signaling was examined at the level of glucocorticoid receptor (GR) expression and compartmental redistribution, as well as at the level of expression of its target genes (GR, phosphoenolpyruvate carboxyl kinase and hormone-sensitive lipase). Fructose diet led to increased 11βHSD1 and H6PDH expression and elevated corticosterone level within the adipose tissue, which was paralleled with enhanced GR nuclear accumulation. Although the animals did not develop obesity, nonesterified fatty acid and plasma triglyceride levels were elevated, indicating that fructose, through enhanced prereceptor metabolism of glucocorticoids, could set the environment for possible later onset of obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

    Science.gov (United States)

    2017-09-01

    individual cell types within human adipose tissue interact to regulate adipose tissue physiology . Specifically, we have developed the molecular and...AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...TYPE Annual 3. DATES COVERED 1 AUG 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of Human Adipose Tissue Stromal

  16. Obesity Determines the Immunophenotypic Profile and Functional Characteristics of Human Mesenchymal Stem Cells From Adipose Tissue.

    Science.gov (United States)

    Pachón-Peña, Gisela; Serena, Carolina; Ejarque, Miriam; Petriz, Jordi; Duran, Xevi; Oliva-Olivera, W; Simó, Rafael; Tinahones, Francisco J; Fernández-Veledo, Sonia; Vendrell, Joan

    2016-04-01

    Adipose tissue is a major source of mesenchymal stem cells (MSCs), which possess a variety of properties that make them ideal candidates for regenerative and immunomodulatory therapies. Here, we compared the immunophenotypic profile of human adipose-derived stem cells (hASCs) from lean and obese individuals, and explored its relationship with the apparent altered plasticity of hASCs. We also hypothesized that persistent hypoxia treatment of cultured hASCs may be necessary but not sufficient to drive significant changes in mature adipocytes. hASCs were obtained from subcutaneous adipose tissue of healthy, adult, female donors undergoing abdominal plastic surgery: lean (n=8; body mass index [BMI]: 23±1 kg/m2) and obese (n=8; BMI: 35±5 kg/m2). Cell surface marker expression, proliferation and migration capacity, and adipogenic differentiation potential of cultured hASCs at two different oxygen conditions were studied. Compared with lean-derived hASCs, obese-derived hASCs demonstrated increased proliferation and migration capacity but decreased lipid droplet accumulation, correlating with a higher expression of human leukocyte antigen (HLA)-II and cluster of differentiation (CD) 106 and lower expression of CD29. Of interest, adipogenic differentiation modified CD106, CD49b, HLA-ABC surface protein expression, which was dependent on the donor's BMI. Additionally, low oxygen tension increased proliferation and migration of lean but not obese hASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile. In summary, the differences observed in proliferation, migration, and differentiation capacity in obese hASCs occurred in parallel with changes in cell surface markers, both under basal conditions and during differentiation. Therefore, obesity is an important determinant of stem cell function independent of oxygen tension. The obesity-related hypoxic environment may have latent effects on human adipose tissue-derived mesenchymal stem cells (hASCs) with

  17. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

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  10. CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

    NARCIS (Netherlands)

    Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG

  11. Distribution of persistent, lipid-soluble chemicals in breast and abdominal adipose tissues: lessons learned from a breast cancer study.

    Science.gov (United States)

    Petreas, Myrto; Smith, Daniel; Hurley, Susan; Jeffrey, Stefanie S; Gilliss, Debra; Reynolds, Peggy

    2004-03-01

    We sought to determine differences between concentrations of persistent, lipid-soluble chemical contaminants in breast and abdominal adipose tissues and to explore whether concentrations measured in one tissue could predict concentrations in the other tissue. We analyzed surgical specimens and measured concentrations of prevalent dioxins, furans, polychlorinated biphenyls, organochlorine pesticides, and brominated diphenyl ethers to determine their partitioning between breast and abdominal adipose tissues of 21 women. The women constituted a subgroup, undergoing mastectomies with simultaneous breast reconstruction, of a case-control study evaluating links between breast cancer and body burdens of organohalogen contaminants. For every contaminant, differences between concentrations in breast and abdominal adipose tissues did not exceed the analytical error. Results indicated that, with some notable exceptions, measurements in breast and abdominal adipose tissues were correlated and that concentrations of target chemicals in one tissue could be derived from measurements in the other tissue. This information will allow comparison of results from body burden studies that used different tissues. It may also facilitate future breast cancer studies by allowing selection of controls among patients undergoing surgical procedures other than breast surgery, minimizing concerns about overmatching. We also observed large differences in the lipid content of surgical specimens. These differences underscore the need for lipid adjustment of concentrations to avoid misclassification.

  12. Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor

    Directory of Open Access Journals (Sweden)

    Veronika Y. Sysoeva

    2017-12-01

    Full Text Available Obesity is often associated with high systemic and local activity of renin-angiotensin system (RAS. Mesenchymal stem cells of adipose tissue are the main source of adipocytes. The aim of this study was to clarify how local RAS could control adipose differentiation of human adipose tissue derived mesenchymal stem cells (ADSCs. We examined the distribution of angiotensin receptor expressing cells in human adipose tissue and found that type 1 and type 2 receptors are co-expressed in its stromal compartment, which is known to contain mesenchymal stem cells. To study the expression of receptors specifically in ADSCs we have isolated them from adipose tissue. Up to 99% of cultured ADSCs expressed angiotensin II (AngII receptor type 1 (AT1. Using the analysis of Ca2+ mobilization in single cells we found that only 5.2 ± 2.7% of ADSCs specifically respond to serial Ang II applications via AT1 receptor and expressed this receptor constantly. This AT1const ADSCs subpopulation exhibited increased adipose competency, which was triggered by endogenous AngII. Inhibitory and expression analyses showed that AT1const ADSCs highly co-express AngII type 2 receptor (AT2, which was responsible for increased adipose competency of this ADSC subpopulation.

  13. Development of volume-stable adipose tissue constructs using polycaprolactone-based polyurethane scaffolds and fibrin hydrogels.

    Science.gov (United States)

    Wittmann, Katharina; Storck, Katharina; Muhr, Christian; Mayer, Helena; Regn, Sybille; Staudenmaier, Rainer; Wiese, Hinrich; Maier, Gerhard; Bauer-Kreisel, Petra; Blunk, Torsten

    2016-10-01

    Adipose tissue engineering aims at the restoration of soft tissue defects and the correction of contour deformities. It is therefore crucial to provide functional adipose tissue implants with appropriate volume stability. Here, we investigate two different fibrin formulations, alone or in combination with biodegradable polyurethane (PU) scaffolds as additional support structures, with regard to their suitability to generate volume-stable adipose tissue constructs. Human adipose-derived stem cells (ASCs) were incorporated in a commercially available fibrin sealant as well as a stable fibrin hydrogel previously developed by our group. The composite constructs made from the commercially available fibrin and porous poly(ε-caprolactone)-based polyurethane scaffolds exhibited increased volume stability as compared to fibrin gels alone; however, only constructs using the stable fibrin gels completely maintained their size and weight for 21 days. Adipogenesis of ASCs was not impaired by the additional PU scaffold. After induction with a common hormonal cocktail, for constructs with either fibrin formulation, strong adipogenic differentiation of ASCs was observed after 21 days in vitro. Furthermore, upregulation of adipogenic marker genes was demonstrated at mRNA (PPARγ, C/EBPα, GLUT4 and aP2; qRT-PCR) and protein (leptin; ELISA) levels. Stable fibrin/PU constructs were further evaluated in a pilot in vivo study, resulting in areas of well-vascularized adipose tissue within the implants after only 5 weeks. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection...... constant. It is concluded that the microvascular volume and changes in volume in abdominal subcutaneous adipose tissue can be assessed using CEU with good reproducibility. Postprandial capillary recruitment takes place in abdominal subcutaneous adipose tissue....

  15. The role of perivascular adipose tissue in vascular smooth muscle cell growth.

    Science.gov (United States)

    Miao, Chao-Yu; Li, Zhi-Yong

    2012-02-01

    Adipose tissue is the largest endocrine organ, producing various adipokines and many other substances. Almost all blood vessels are surrounded by perivascular adipose tissue (PVAT), which has not received research attention until recently. This review will discuss the paracrine actions of PVAT on the growth of underlying vascular smooth muscle cells (VSMCs). PVAT can release growth factors and inhibitors. Visfatin is the first identified growth factor derived from PVAT. Decreased adiponectin and increased tumour necrosis factor-α in PVAT play a pathological role for neointimal hyperplasia after endovascular injury. PVAT-derived angiotensin II, angiotensin 1-7, reactive oxygen species, complement component 3, NO and H(2) S have a paracrine action on VSMC contraction, endothelial or fibroblast function; however, their paracrine actions on VSMC growth remain to be directly verified. Factors such as monocyte chemoattractant protein-1, interleukin-6, interleukin-8, leptin, resistin, plasminogen activator inhibitor type-1, adrenomedullin, free fatty acids, glucocorticoids and sex hormones can be released from adipose tissue and can regulate VSMC growth. Most of them have been verified for their secretion by PVAT; however, their paracrine functions are unknown. Obesity, vascular injury, aging and infection may affect PVAT, causing adipocyte abnormality and inflammatory cell infiltration, inducing imbalance of PVAT-derived growth factors and inhibitors, leading to VSMC growth and finally resulting in development of proliferative vascular disease, including atherosclerosis, restenosis and hypertension. In the future, using cell-specific gene interventions and local treatments may provide definitive evidence for identification of key factor(s) involved in PVAT dysfunction-induced vascular disease and thus may help to develop new therapies. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http

  16. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy.

    Science.gov (United States)

    Li, Chun-yu; Wu, Xiao-yun; Tong, Jia-bei; Yang, Xin-xin; Zhao, Jing-li; Zheng, Quan-fu; Zhao, Guo-bin; Ma, Zhi-jie

    2015-04-13

    Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapies. Human platelet lysate represents an efficient alternative to fetal bovine serum for clinical-scale expansion of MSCs. Different media used in culture processes should maintain the biological characteristics of MSCs during multiple passages. However, bone marrow-derived MSCs and adipose tissue-derived MSCs have not yet been directly compared with each other under human platelet lysate conditions. This study aims to conduct a direct head-to-head comparison of the biological characteristics of the two types of MSCs under human platelet lysate-supplemented culture conditions for their ability to be used in regenerative medicine applications. The bone marrow- and adipose tissue-derived MSCs were cultured under human platelet lysate conditions and their biological characteristics evaluated for cell therapy (morphology, immunophenotype, colony-forming unit-fibroblast efficiency, proliferation capacity, potential for mesodermal differentiation, secreted proteins, and immunomodulatory effects). Under human platelet lysate-supplemented culture conditions, bone marrow- and adipose tissue-derived MSCs exhibited similar fibroblast-like morphology and expression patterns of surface markers. Adipose tissue-derived MSCs had greater proliferative potential than bone marrow-derived MSCs, while no significantly difference in colony efficiency were observed between the two types of cells. However, bone marrow-derived MSCs possessed higher capacity toward osteogenic and chondrogenic differentiation compared with adipose tissue-derived MSCs, while similar adipogenic differentiation potential wase observed between the two types of cells. There were some differences between bone marrow- and adipose tissue-derived MSCs for several secreted proteins, such as cytokine (interferon-γ), growth factors (basic fibroblast growth factor, hepatocyte growth factor, and insulin-like growth factor-1), and chemokine (stem

  17. The role of metformin and resveratrol in the prevention of hypoxia‐inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue

    Science.gov (United States)

    Li, Xiaole; Li, Jia; Wang, Lulu; Li, Aiyun; Qiu, Zhixia; Qi, Lian‐wen; Kou, Junping; Liu, Kang; Liu, Baolin

    2016-01-01

    Background and Purpose Hypoxic activation of hypoxia‐inducible factor 1α (HIF‐1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF‐1α and fibrosis in hypoxic adipose tissue. Experimental Approach Mice were fed a high‐fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF‐1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro‐inflammatory cytokines were examined. Key Results Oral administration of metformin or resveratrol prevented hypoxia and reduced HIF‐1α accumulation with dephosphorylation of inositol‐requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF‐1α activation and endoplasmic reticulum stress. Metformin and resveratrol down‐regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF‐α, IL‐6, monocyte chemoattractant protein 1 and F4/80 were also down‐regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2. Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3‐L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF‐1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1. Conclusion and Implications Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF‐1α activation‐induced fibrosis and inflammation in adipose tissue, although by different mechanisms. PMID:27059094

  18. The role of metformin and resveratrol in the prevention of hypoxia-inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue.

    Science.gov (United States)

    Li, Xiaole; Li, Jia; Wang, Lulu; Li, Aiyun; Qiu, Zhixia; Qi, Lian-Wen; Kou, Junping; Liu, Kang; Liu, Baolin; Huang, Fang

    2016-06-01

    Hypoxic activation of hypoxia-inducible factor 1α (HIF-1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF-1α and fibrosis in hypoxic adipose tissue. Mice were fed a high-fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF-1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro-inflammatory cytokines were examined. Oral administration of metformin or resveratrol prevented hypoxia and reduced HIF-1α accumulation with dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF-1α activation and endoplasmic reticulum stress. Metformin and resveratrol down-regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF-α, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2 . Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3-L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF-1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1. Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF-1α activation-induced fibrosis and inflammation in adipose tissue, although by different mechanisms. © 2016 The British Pharmacological Society.

  19. Explant culture: a simple, reproducible, efficient and economic technique for isolation of mesenchymal stromal cells from human adipose tissue and lipoaspirate.

    Science.gov (United States)

    Priya, Nancy; Sarcar, Shilpita; Majumdar, Anish Sen; SundarRaj, Swathi

    2014-09-01

    Adipose tissue has emerged as a preferred source of mesenchymal stem/stromal cells (MSC), due to its easy accessibility and high MSC content. The conventional method of isolation of adipose tissue-derived stromal cells (ASC) involves enzymatic digestion and centrifugation, which is a costly and time-consuming process. Mechanical stress during isolation, use of bacterial-derived products and potential contamination with endotoxins and xenoantigens are other disadvantages of this method. In this study, we propose explant culture as a simple and efficient process to isolate ASC from human adipose tissue. This technique can be used to reproducibly isolate ASC from fat tissue obtained by liposuction as well as surgical resection, and yields an enriched ASC population free from contaminating haematopoietic cells. We show that explanting adipose tissue results in a substantially higher yield of ASC at P0 per gram of initial fat tissue processed, as compared to that obtained by enzymatic digestion. We demonstrate that ASC isolated by explant culture are phenotypically and functionally equivalent to those obtained by enzymatic digestion. Further, the explant-derived ASC share the immune privileged status and immunosuppressive properties implicit to MSC, suggesting that they are competent to be tested and applied in allogeneic clinical settings. As explant culture is a simple, inexpensive and gentle method, it may be preferred over the enzymatic technique for obtaining adipose tissue-derived stem/stromal cells for tissue engineering and regenerative medicine, especially in cases of limited starting material. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

    Directory of Open Access Journals (Sweden)

    Meenakshi Gaur

    2017-01-01

    Full Text Available Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

  1. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Delphine Duteil

    2016-10-01

    Full Text Available Previous work indicated that lysine-specific demethylase 1 (Lsd1 can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.

  2. Isolation of Stromal Stem Cells from Adipose Tissue.

    Science.gov (United States)

    Prat, Maria; Oltolina, Francesca; Antonini, Silvia; Zamperone, Andrea

    2017-01-01

    Adipose tissue has been shown to be particularly advantageous as source of mesenchymal stem cells (MSCs), because of its easy accessibility, and the possibility of obtaining stem cells in high yields. MSCs are obtained from the so-called Stromal Vascular Fraction, (SVF), exploiting their property of adhering to plastic surfaces and can be further purified by positive or negative immunomagnetic selection with appropriately chosen antibodies. These cells (Stromal Stem Cells, SSCs) can then be directly analyzed, frozen in liquid nitrogen, or expanded for further applications, e.g., for tissue engineering and regenerative medicine. The methodology described here in detail for SSCs isolated from mouse subcutaneous adipose tissue can be applied to human tissues, such as epicardium.

  3. Heterogeneous response of adipose tissue to cancer cachexia

    Directory of Open Access Journals (Sweden)

    P.S. Bertevello

    2001-09-01

    Full Text Available Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES, retroperitoneal (RPAT, and epididymal (EAT adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections and EAT (nuclear bodies.

  4. Thermogenic potential and physiological relevance of human epicardial adipose tissue

    Science.gov (United States)

    Chechi, K; Richard, D

    2015-01-01

    Epicardial adipose tissue is a unique fat depot around the heart that shares a close anatomic proximity and vascular supply with the myocardium and coronary arteries. Its accumulation around the heart, measured using various imaging modalities, has been associated with the onset and progression of coronary artery disease in humans. Epicardial adipose tissue is also the only fat depot around the heart that is known to express uncoupling protein 1 at both mRNA and protein levels in the detectable range. Recent advances have further indicated that human epicardial fat exhibits beige fat-like features. Here we provide an overview of the physiological and pathophysiological relevance of human epicardial fat, and further discuss whether its thermogenic properties can serve as a target for the therapeutic management of coronary heart disease in humans. PMID:27152172

  5. Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development.

    Science.gov (United States)

    Tremolada, Carlo; Colombo, Valeria; Ventura, Carlo

    In the past few years, interest in adipose tissue as an ideal source of mesenchymal stem cells (MSCs) has increased. These cells are multipotent and may differentiate in vitro into several cellular lineages, such as adipocytes, chondrocytes, osteoblasts, and myoblasts. In addition, they secrete many bioactive molecules and thus are considered "mini-drugstores." MSCs are being used increasingly for many clinical applications, such as orthopedic, plastic, and reconstructive surgery. Adipose-derived MSCs are routinely obtained enzymatically from fat lipoaspirate as SVF and/or may undergo prolonged ex vivo expansion, with significant senescence and a decrease in multipotency, leading to unsatisfactory clinical results. Moreover, these techniques are hampered by complex regulatory issues. Therefore, an innovative technique (Lipogems®; Lipogems International SpA, Milan, Italy) was developed to obtain microfragmented adipose tissue with an intact stromal vascular niche and MSCs with a high regenerative capacity. The Lipogems® technology, patented in 2010 and clinically available since 2013, is an easy-to-use system designed to harvest, process, and inject refined fat tissue and is characterized by optimal handling ability and a great regenerative potential based on adipose-derived MSCs. In this novel technology, the adipose tissue is washed, emulsified, and rinsed and adipose cluster dimensions gradually are reduced to about 0.3 to 0.8 mm. In the resulting Lipogems® product, pericytes are retained within an intact stromal vascular niche and are ready to interact with the recipient tissue after transplantation, thereby becoming MSCs and starting the regenerative process. Lipogems® has been used in more than 7000 patients worldwide in aesthetic medicine and surgery, as well as in orthopedic and general surgery, with remarkable and promising results and seemingly no drawbacks. Now, several clinical trials are under way to support the initial encouraging outcomes

  6. Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues

    OpenAIRE

    Contreras, G. Andres; Strieder-Barboza, Clarissa; de Souza, Jonas; Gandy, Jeff; Mavangira, Vengai; Lock, Adam L.; Sordillo, Lorraine M.

    2017-01-01

    The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of ...

  7. Brain–gut–adipose-tissue communication pathways at a glance

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi

    2012-09-01

    Full Text Available One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

  8. Molecular clock integration of brown adipose tissue formation and function

    OpenAIRE

    Nam, Deokhwa; Yechoor, Vijay K.; Ma, Ke

    2015-01-01

    Abstract The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circ...

  9. Systems genetic analysis of brown adipose tissue function

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Saba, L. M.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Hüttl, M.; Marková, I.; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Smith, H.; Tabakoff, B.

    2018-01-01

    Roč. 50, č. 1 (2018), s. 52-66 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * coexpression modules * quantitative trait locus * recombinant inbred strains * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Human genetics Impact factor: 3.044, year: 2016

  10. The influence of perivascular adipose tissue on vascular homeostasis

    OpenAIRE

    Szasz T; Bomfim GF; Webb RC

    2013-01-01

    Theodora Szasz,1 Gisele Facholi Bomfim,2 R Clinton Webb1 1Department of Physiology, Georgia Regents University, Augusta, USA; 2Department of Pharmacology, University of São Paulo, São Paulo, Brazil Abstract: The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle...

  11. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  12. Food consumption and adipose tissue DDT levels in Mexican women

    Directory of Open Access Journals (Sweden)

    Marcia Galván-Portillo

    2002-04-01

    Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

  13. Food consumption and adipose tissue DDT levels in Mexican women

    Directory of Open Access Journals (Sweden)

    Galván-Portillo Marcia

    2002-01-01

    Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

  14. Functionally enhanced brown adipose tissue in Ames dwarf mice.

    Science.gov (United States)

    Darcy, Justin; Bartke, Andrzej

    2017-01-02

    Reduced insulin-like growth factor 1/insulin signaling (IIS) has been linked to extended longevity in species ranging from yeast to mammals. In mammals, this is exemplified in Ames dwarf (Prop1 df/df ) mice, which have a 40%-60% increase in longevity (males and females, respectively) due to their recessive Prop1 loss-of-function mutation that results in lack of growth hormone (GH), thyroid-stimulating hormone and prolactin. Our laboratory has previously shown that Ames dwarf mice have functionally unique white adipose tissue (WAT) that improves, rather than impairs, insulin sensitivity. Because GH and thyroid hormone are integral to adipose tissue development and function, we hypothesized that brown adipose tissue (BAT) in Ames dwarf mice may also be functionally unique and/or enhanced. Here, we elaborate on our recent findings, which demonstrate that BAT is functionally enhanced in Ames dwarf mice, and suggest that BAT removal in these mice results in utilization of WAT depots as an energy source. We also discuss how our findings compare to those in other long-lived dwarf mice with altered IIS, which unlike Ames dwarf mice, are essentially euthyroid. Lastly, we provide some insights into the implications of these findings and discuss some of the necessary future work in this area.

  15. [The adipose tissue as a regulatory center of the metabolism].

    Science.gov (United States)

    Fonseca-Alaniz, Miriam H; Takada, Julie; Alonso-Vale, Maria Isabel C; Lima, Fabio Bessa

    2006-04-01

    The recent progress in the research about the metabolic properties of the adipose tissue and the discovery of its ability to produce hormones that are very active in pathophysiologic as well as physiologic processes is rebuilding the concepts about its biology. Its involvement in conditions like obesity, type 2 diabetes mellitus, arterial hypertension, arteriosclerosis, dislipidemias and chronic and acute inflammatory processes indicate that the understanding of its functional capacities may contribute to improve the prognosis of those diseases whose prevalence increased in a preoccupying manner. Here we review some functional aspects of adipocytes, such as the metabolism, its influence on energy homeostasis, its endocrine ability and the adipogenesis, i.e., the potential of pre-adipocytes present in adipose tissue stroma to differentiate into new adipocytes and regenerate the tissue. In addition, we are including some studies on the relationship between the adipose tissue and the pineal gland, a new and poorly known, although, as will be seen, very promising aspect of adipocyte physiology together with its possible favorable repercussions to the therapy of the obesity related diseases.

  16. Nitro-fatty acid pharmacokinetics in the adipose tissue compartment.

    Science.gov (United States)

    Fazzari, Marco; Khoo, Nicholas K H; Woodcock, Steven R; Jorkasky, Diane K; Li, Lihua; Schopfer, Francisco J; Freeman, Bruce A

    2017-02-01

    Electrophilic nitro-FAs (NO 2 -FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports posttranslational protein modifications. A unique pharmacokinetic profile is expected for NO 2 -FAs because of an ability to undergo reversible reactions including Michael addition with cysteine-containing proteins and esterification into complex lipids. Herein, we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[ 14 C]oleic acid, preferential accumulation in adipose tissue over 2 weeks. To better define the metabolism and incorporation of NO 2 -FAs and their metabolites in adipose tissue lipids, adipocyte cultures were supplemented with 10-nitro-oleic acid (10-NO 2 -OA), nitro-stearic acid, nitro-conjugated linoleic acid, and nitro-linolenic acid. Then, quantitative HPLC-MS/MS analysis was performed on adipocyte neutral and polar lipid fractions, both before and after acid hydrolysis of esterified FAs. NO 2 -FAs preferentially incorporated in monoacyl- and diacylglycerides, while reduced metabolites were highly enriched in triacylglycerides. This differential distribution profile was confirmed in vivo in the adipose tissue of NO 2 -OA-treated mice. This pattern of NO 2 -FA deposition lends new insight into the unique pharmacokinetics and pharmacologic actions that could be expected for this chemically-reactive class of endogenous signaling mediators and synthetic drug candidates. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  17. Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats

    Science.gov (United States)

    We reported previously that a dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molec...

  18. 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...

  19. Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet.

    Science.gov (United States)

    Huang, Da-Wei; Chang, Wen-Chang; Yang, Heng-Jui; Wu, James Swi-Bea; Shen, Szu-Chuan

    2018-01-15

    This study investigated the ameliorative effect of gallic acid (GA) on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD)-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight) for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG) in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study ( p perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK) and pyruvate kinase (PK), and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL), which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM) complications.

  20. Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet

    Directory of Open Access Journals (Sweden)

    Da-Wei Huang

    2018-01-01

    Full Text Available This study investigated the ameliorative effect of gallic acid (GA on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study (p < 0.05. Western blot assay indicated that GA restored expression of insulin signaling-related proteins, such as insulin receptor (IR, protein kinase C-zeta (PKC-ζ, and glucose transporter-4 (GLUT4 in the perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK and pyruvate kinase (PK, and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL, which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM complications.

  1. Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues.

    Directory of Open Access Journals (Sweden)

    G Andres Contreras

    Full Text Available The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT, which induces the release of free fatty acids (FFA into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids such as hydroxy-octadecadienoic acids (HODE and hydroxy-eicosatetraenoic acids (HETE, were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis. However, the effect of lipolysis intensity during the transition from gestation to lactation on fatty acid substrate availability and subsequent AT oxylipid biosynthesis is currently unknown. We hypothesized that in periparturient dairy cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide with changes in lipolysis intensity and stage of lactation. Blood and subcutaneous AT samples were collected from periparturient cows at -27±7 (G1 and -10±5 (G2 d prepartum and at 8±3 d postpartum (PP. Targeted lipidomic analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA concentrations increased as parturition approached and were highest at PP. Cows exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L had higher body condition scores at G1 compared to cows with low lipolysis rate (FFA<1.0 mEq/L. Concentrations of plasma linoleic and arachidonic acids were increased at PP. In AT, 13-HODE, and 5-, 11- and 15-HETE were increased at PP compared to G1 and G2. Concentrations of beta hydroxybutyrate were positively correlated with those of 13-HODE and 15-HETE in AT. Plasma concentrations of 5- and 20-HETE were increased at PP. These data demonstrate that prepartum adiposity predisposes cows to intense lipolysis post-partum and may exacerbate AT inflammation because of increased production of pro-inflammatory oxylipids including 5- and 15-HETE and 13-HODE. These results

  2. Does measurement site for visceral and abdominal subcutaneous adipose tissue alter associations with the metabolic syndrome?

    Science.gov (United States)

    Kuk, Jennifer L; Church, Timothy S; Blair, Steven N; Ross, Robert

    2006-03-01

    To determine whether the associations between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and the metabolic syndrome are altered depending on measurement site for VAT and ASAT and the definition used to identify the metabolic syndrome. Total VAT and ASAT volume was derived using approximately 37 contiguous computed tomography (CT) images from T10-T11 to L5-S1 in 85 men. CT images obtained at eight intervertebral locations (e.g., L4-L5, L3-L4, etc.) were used to determine the associations between partial volumes (single images) and metabolic syndrome. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Logistic regression was used to calculate the odds ratio (OR) per SD increase in adipose tissue. For total and all partial volumes, VAT was more strongly associated with metabolic syndrome than ASAT independent of metabolic syndrome criteria. The OR (per SD) for NCEP metabolic syndrome was higher for total VAT volume (OR = 7.26) and for the partial volumes at T12-L1 (7.46) and L1-L2 (8.77) than those at the L4-L5 level (3.94). The OR for metabolic syndrome ( approximately 2.6) was not substantially different among the ASAT measures. A similar pattern of association was observed using the IDF metabolic syndrome criteria. The measurement site for VAT, but not for ASAT, has a substantial influence on the magnitude of the association with both metabolic syndrome definitions. However, because VAT remained significantly associated with metabolic syndrome regardless of measurement site, the clinical interpretation was unaltered by measurement protocol or metabolic syndrome definition.

  3. Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera.

    Science.gov (United States)

    Koh, Kyung Suk; Oh, Tae Suk; Kim, Hoon; Chung, In Wook; Lee, Kang Woo; Lee, Hyo Bo; Park, Eun Jung; Jung, Jae Seob; Shin, Il Seob; Ra, Jeong Chan; Choi, Jong Woo

    2012-09-01

    Parry-Romberg disease is a rare condition that results in progressive hemifacial atrophy, involving the skin, dermis, subcutaneous fat, muscle, and, finally, cartilage and bone. Patients have been treated with dermofat or fat grafts or by microvascular free flap transfer. We hypothesized that adipose-derived stem cells (ASCs) may improve the results of microfat grafting through enhancing angiogenesis. We evaluated the utility of ASC in microfat grafting of patients with Parry-Romberg disease by measuring the change in the hemifacial volumes after injection of ASCs with microfat grafts or microfat grafts alone. In April 2008, this investigation was approved by the Korean Food and Drug Administration and the institutional review board of the Asan Medical Center (Seoul, Korea) that monitor investigator-initiated trials. Between May 2008 and January 2009, 10 volunteers with Parry-Romberg disease (5 men and 5 women; mean age, 28 y) were recruited; 5 received ASC and microfat grafts and 5 received microfat grafts only. The mean follow-up period was 15 months. Adipose-derived stem cells were obtained from abdominal fat by liposuction and were cultured for 2 weeks. On day 14, patients were injected with fat grafts alone or plus (in the test group) 1 × 10 ASCs. Patients were evaluated postoperatively using a 3-dimensional camera and 3-dimensional CT scans, and grafted fat volumes were objectively calculated. Successful outcomes were evident in all 5 patients receiving microfat grafts and ASCs, and the survival of grafted fat was better than in patients receiving microfat grafts alone. Before surgery, the mean difference between ipsilateral and contralateral hemiface volume in patients receiving microfat grafts and ASCs was 21.71 mL decreasing to 4.47 mL after surgery. Overall resorption in this ASC group was 20.59%. The mean preoperative difference in hemiface volume in those receiving microfat grafts alone was 8.32 mL decreasing to 3.89 mL after surgery. Overall

  4. Regeneration of Skin Surface by Multipotent Mesenchymal Stem Cells of Adipose Tissue in Laboratory Animals with Infected Wounds

    OpenAIRE

    Sahab, A. Haydar; Tretyak, S.; Nedzved, M.K.; Baranov, E.V.; Nadyrov, E.; Lobanok, H.H.; Vasilevich, I.B.; Welcome, M.O.

    2013-01-01

    This paper presents results of experimental studies in laboratory animals with a simulated infected wound, for which mesenchymal stem cells (MSCs) derived from adipose tissue were used in its treatment. The following peculiarities of MSCs for regeneration of skin defects are established: faster arrest of inflammation, accelerated wound healing processes, as well as observed stimulation of growth of skin appendages. The results of this study may serve the basis for further research from develo...

  5. Pre-medication to block [18F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients

    International Nuclear Information System (INIS)

    Gelfand, Michael J.; O'Hara, Sara M.; Curtwright, Lois A.; MacLean, Joseph R.

    2005-01-01

    Radiopharmaceutical uptake of [ 18 F]2-deoxy-2-glucose (FDG) in brown adipose tissue is noted on 15-20% of positron emission tomography (PET) scans in children and adolescents. To determine whether [ 18 F]FDG uptake in brown adipose tissue can be adequately blocked by pre-medication other than moderate-dose oral diazepam. One hundred and eighteen [ 18 F]FDG PET body imaging studies were performed in 69 pediatric patients with a variety of solid tumors. The mean age at the time of imaging was 12.9 years (range 1.2-22.6 years), and 33 studies were performed in patients younger than 10 years old. Seventy-six were performed in boys and 42 in girls. Patients were imaged using a dedicated PET camera. Pre-medication was given in 88 studies: 45 received intravenous fentanyl (0.75-1.0 μg/kg), 34 received low-dose oral diazepam (0.06 mg/kg) and 9 received moderate-dose oral diazepam (0.10 mg/kg). Thirty patients received no pre-medication, 7 of whom were known to have received opiates for pain during the 12 h before the study. Six body regions in the neck and chest were reviewed for [ 18 F]FDG uptake in brown adipose tissue. Uptake of FDG in brown fat was visually graded: 0 for no FDG uptake, 1 for low-grade uptake, 2 for moderate uptake, and 3 for intense uptake. Visual grades 2 and 3 were considered to interfere potentially with image interpretation in the neck and chest. Data were analyzed by multivariate regression using a Poisson distribution. [ 18 F]FDG uptake in brown adipose tissue was most often seen in the lateral neck region and superior and lateral to the lungs (in 36 and 39 studies, respectively). Uptake was also seen near the costovertebral junctions (15 studies), in the superior and central neck in 7 studies and in the anterior mediastinum in 2. Brown adipose tissue uptake was thought to interfere potentially with image interpretation (visual grades 2 and 3) in 19 studies - in 6 of 23 (26.1%) studies after no pre-medication and no opiates for pain, in 10 of

  6. Organochlorine pesticide levels in female adipose tissue from Puebla, Mexico.

    Science.gov (United States)

    Waliszewski, Stefan M; Sanchez, K; Caba, M; Saldariaga-Noreña, H; Meza, E; Zepeda, R; Valencia Quintana, R; Infanzon, R

    2012-02-01

    The objective of this study was to determine the levels of organochlorine pesticides HCB, α-β-γ-HCH, pp'DDE, op'DDT and pp'DDT in adipose tissue of females living in Puebla, Mexico. Organochlorine pesticides were analyzed in 75 abdominal adipose tissue samples taken during 2010 by autopsy at the Forensic Services of Puebla. The results were expressed as mg/kg on fat basis. In analyzed samples the following pesticides were detected: p,p'-DDE in 100% of samples at mean 1.464 mg/kg; p,p'-DDT in 96.0.% of samples at mean 0.105 mg/kg; op'DDT in 89.3% of monitored samples at mean 0.025 mg/kg and β-HCH in 94.7% of the samples at mean 0.108 mg/kg. To show if organochlorine pesticide levels in monitored female's adipose tissues are age dependant, the group was divided in three ages ranges (13-26, 26-57 and 57-96 years). The mean and median levels of all organochlorine pesticides increase significantly (p 0.05). The present results compared to previous ones from 2008 indicates an increase in the concentrations during the 2010 study, but only the differences for pp'DDE and op'DDT were statistically significant. The 2010 group of females was older compared to the 2008 group. The presence of organochlorine pesticide residues is still observed, indicating uniform and permanent exposure to the pesticides by Puebla inhabitants.

  7. Isolation of Mesenchymal Stem Cells from Adipose Tissue

    OpenAIRE

    Islam, Andi Asadul

    2015-01-01

    BACKGROUND: In searching for the best source of stem cells, researcher found adipose stem cells as one of the ideal source due to its easiness in harvesting and its potential for differentiating into other cell lineage. METHODS: We isolated stem cells from adipose tissue, cultured and confirmed its immunophenotype using polymerase chain reaction. RESULTS: Cluster of differentiation (CD)44, CD73, CD90, CD105 were expressed, which represent immunophenotype of mesenchymal stem cells.  CONCLUSION...

  8. n-3 PUFA: bioavailability and modulation of adipose tissue function

    Czech Academy of Sciences Publication Activity Database

    Kopecký, Jan; Rossmeisl, Martin; Flachs, Pavel; Kuda, Ondřej; Brauner, Petr; Jílková, Zuzana; Staňková, B.; Tvrzická, E.; Bryhn, M.

    2009-01-01

    Roč. 68, č. 4 (2009), s. 361-369 ISSN 0029-6651. [Meeting of the Nutrition Society. Edinburgh, 07.04.2009-08.04.2009] R&D Projects: GA ČR(CZ) GA303/08/0664; GA ČR(CZ) GD305/08/H037 Grant - others:EC(XE) LSHM-CT-2004-005272 Institutional research plan: CEZ:AV0Z50110509 Keywords : n-3 PUFA * DHA * adipose tissue Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.321, year: 2009

  9. Comparison of TGF-β1 and NO production by mesenchymal stem cells isolated from murine lung and adipose tissues.

    Science.gov (United States)

    Hosseinpur, Zahra; Hashemi, Seyed Mahmoud; Salehi, Eisa; Ghazanfari, Tooba

    2016-06-01

    Mesenchymal stem cells (MSCs) are cell sources for tissues regeneration. By secretion of soluble factors including transforming growth factor-β (TGF-β1) and nitric oxide (NO), MSCs are also able to regulate the immune system. MSCs have been disclosed in lung and adipose tissues with insufficient comparison between the tissues. In this study, specific differentiation and the expression of surface antigens as well as TGF-β1 and NO productive levels were compared in murine lung-derived MSCs (LMSCs) and adipose tissue-derived MSCs (ADMSCs). MSCs were isolated from murine lung and adipose tissues and cultured. Both cell populations were characterized using multilineage potential and the expression of surface antigenic proteins, CD73, CD105, CD34, CD45, and CD11b. Finally, levels of TGF-β1 and NO were evaluated and compared in ADMSCs and LMSCs. Expression of CD73 and CD105; lack of the expression of CD34, CD45, and CD11b markers; as well as adipocyte and osteocyte differentiations were detected in both adult stem cells. No significant difference was found in TGF-β1 and NO production between two stem cell populations. Our data showed that LMSCs and ADMSCs have comparable phenotype and TGF-β1 and NO production.

  10. Roles of gastrointestinal and adipose tissue peptides in childhood obesity and changes after weight loss due to lifestyle intervention.

    Science.gov (United States)

    Roth, Christian L; Reinehr, Thomas

    2010-02-01

    Childhood obesity is a global epidemic and associated with an increased risk of hypertension, diabetes mellitus, and coronary heart disease, in addition to psychological disorders. Interventions such as bariatric surgery are highly invasive and lifestyle modifications are often unsuccessful because of disturbed perceptions of satiety. New signaling peptides discovered in recent years that are produced in peripheral tissues such as the gut, adipose tissue, and pancreas communicate with brain centers of energy homeostasis, such as the hypothalamus and hindbrain. This review discusses the major known gut- and adipose tissue-derived hormones involved in the regulation of food intake and energy homeostasis and their serum levels in childhood obesity before and after weight loss as well as their relationship to consequences of obesity. Since most of the changes of gastrointestinal hormones and adipokines normalize in weight loss, pharmacological interventions based on these hormones will likely not solve the obesity epidemic in childhood. However, a better understanding of the pathways of body weight- and food intake-regulating gut- and adipose tissue-derived hormones will help to find new strategies to treat obesity and its consequences.

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

    OpenAIRE

    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-...

  12. Role of the sympathoadrenergic system in adipose tissue metabolism during exercise in humans

    DEFF Research Database (Denmark)

    Stallknecht, B; Lorentsen, J; Enevoldsen, L H

    2001-01-01

    .8 +/- 0.7 ml (100 g)(-1) min(-1) (Cl), 0.6 +/- 0.3 ml (100 g)(-1) min(-1) (Um)). Accordingly, in both adipose tissues lipolysis increased less in SCI compared with healthy subjects, indicating that circulating catecholamines are important for the exercise-induced increase in subcutaneous adipose tissue...... (P important for the exercise-induced increase in subcutaneous adipose tissue lipolysis while sympathetic nerve activity is not....

  13. A Protein Profile of Visceral Adipose Tissues Linked to Early Pathogenesis of Type 2 Diabetes Mellitus*

    OpenAIRE

    Kim, Su-Jin; Chae, Sehyun; Kim, Hokeun; Mun, Dong-Gi; Back, Seunghoon; Choi, Hye Yeon; Park, Kyong Soo; Hwang, Daehee; Choi, Sung Hee; Lee, Sang-Won

    2014-01-01

    Adipose tissue is increasingly recognized as an endocrine organ playing important pathophysiological roles in metabolic abnormalities, such as obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). In particular, visceral adipose tissue (VAT), as opposed to subcutaneous adipose tissue, is closely linked to the pathogenesis of insulin resistance and T2DM. Despite the importance of VAT, its molecular signatures related to the pathogenesis of T2DM have not been systematically expl...

  14. Extracellular vesicles from adipose tissue - a potential role in obesity and type 2 diabetes?

    OpenAIRE

    Gao, Xuan; Salomon, Carlos; Freeman, Dilys J.

    2017-01-01

    Adipose tissue plays a key role in the development of insulin resistance and its pathological sequelae, such as type 2 diabetes and non-alcoholic fatty liver disease. Dysfunction in the adipose tissue response to storing excess fatty acids as triglyceride can lead to adipose tissue inflammation and spillover of fatty acids from this tissue and accumulation of fatty acids as lipid droplets in ectopic sites, such as liver and muscle. Extracellular vesicles (EVs) are released from adipocytes and...

  15. Hypothalamic regulation of brown adipose