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Sample records for adipose-derived stromo-vascular fraction

  1. Gene expression profiles in Atlantic salmon adipose-derived stromo-vascular fraction during differentiation into adipocytes

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    Škugor Stanko

    2010-01-01

    Full Text Available Abstract Background Excessive fat deposition is one of the largest problems faced by salmon aquaculture industries, leading to production losses due to high volume of adipose tissue offal. In addition, increased lipid accumulation may impose considerable stress on adipocytes leading to adipocyte activation and production and secretion of inflammatory mediators, as observed in mammals. Results Microarray and qPCR analyses were performed to follow transcriptome changes during adipogenesis in the primary culture of adipose stromo-vascular fraction (aSVF of Atlantic salmon. Cellular heterogeneity decreased by confluence as evidenced by the down-regulation of markers of osteo/chondrogenic, myogenic, immune and vasculature lineages. Transgelin (TAGLN, a marker of the multipotent pericyte, was prominently expressed around confluence while adipogenic PPARγ was up-regulated already in subconfluent cells. Proliferative activity and subsequent cell cycle arrest were reflected in the fluctuations of pro- and anti-mitotic regulators. Marked regulation of genes involved in lipid and glucose metabolism and pathways producing NADPH and glycerol-3-phosphate (G3P was seen during the terminal differentiation, also characterised by diverse stress responses. Activation of the glutathione and thioredoxin antioxidant systems and changes in the iron metabolism suggested the need for protection against oxidative stress. Signs of endoplasmic reticulum (ER stress and unfolded protein response (UPR occured in parallel with the increased lipid droplet (LD formation and production of secretory proteins (adipsin, visfatin. The UPR markers XBP1 and ATF6 were induced together with genes involved in ubiquitin-proteasome and lysosomal proteolysis. Concurrently, translation was suppressed as evidenced by the down-regulation of genes encoding elongation factors and components of the ribosomal machinery. Notably, expression changes of a panel of genes that belong to different

  2. Analysis for apoptosis and necrosis on adipocytes, stromal vascular fraction, and adipose-derived stem cells in human lipoaspirates after liposuction.

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    Wang, Wei Z; Fang, Xin-Hua; Williams, Shelley J; Stephenson, Linda L; Baynosa, Richard C; Wong, Nancy; Khiabani, Kayvan T; Zamboni, William A

    2013-01-01

    Adipose-derived stem cells have become the most studied adult stem cells. The authors examined the apoptosis and necrosis rates for adipocyte, stromal vascular fraction, and adipose-derived stem cells in fresh human lipoaspirates. Human lipoaspirate (n = 8) was harvested using a standard liposuction technique. Stromal vascular fraction cells were separated from adipocytes and cultured to obtain purified adipose-derived stem cells. A panel of stem cell markers was used to identify the surface phenotypes of cultured adipose-derived stem cells. Three distinct stem cell subpopulations (CD90/CD45, CD105/CD45, and CD34/CD31) were selected from the stromal vascular fraction. Apoptosis and necrosis were determined by annexin V/propidium iodide assay and analyzed by flow cytometry. The cultured adipose-derived stem cells demonstrated long-term proliferation and differentiation evidenced by cell doubling time and positive staining with oil red O and alkaline phosphatase. Isolated from lipoaspirates, adipocytes exhibited 19.7 ± 3.7 percent apoptosis and 1.1 ± 0.3 percent necrosis; stromal vascular fraction cells revealed 22.0 ± 6.3 percent of apoptosis and 11.2 ± 1.9 percent of necrosis; stromal vascular fraction cells had a higher rate of necrosis than adipocytes (p vascular fraction cells, 51.1 ± 3.7 percent expressed CD90/CD45, 7.5 ± 1.0 percent expressed CD105/CD45, and 26.4 ± 3.8 percent expressed CD34/CD31. CD34/CD31 adipose-derived stem cells had lower rates of apoptosis and necrosis compared with CD105/CD45 adipose-derived stem cells (p necrosis than adipocytes. However, the extent of apoptosis and necrosis was significantly different among adipose-derived stem cell subpopulations.

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

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    Mehdi Behfar

    2011-11-01

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

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

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    Gesiane Ribeiro

    2013-12-01

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

  5. The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

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    van Dongen, Joris A.; Stevens, Hieronymus P.; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C.

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be

  6. Hair follicle growth by stromal vascular fraction-enhanced adipose transplantation in baldness

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    Perez-Meza D

    2017-07-01

    Full Text Available David Perez-Meza,1 Craig Ziering,2 Marcos Sforza,3 Ganesh Krishnan,4 Edward Ball,5 Eric Daniels6 1Ziering Medical, Marbella, Spain; 2Ziering Medical, Los Angeles, CA, USA; 3The Hospital Group, Bromsgrove, Worcestershire, 4Ziering Medical, Birmingham, 5Ziering Medical, London, UK; 6Kerastem Technologies, San Diego, CA, USA Abstract: Great interest remains in finding new and emerging therapies for the treatment of male and female pattern hair loss. The autologous fat grafting technique is >100 years old, with a recent and dramatic increase in clinical experience over the past 10–15 years. Recently, in 2001, Zuk et al published the presence of adipose-derived stem cells, and abundant research has shown that adipose is a complex, biological active, and important tissue. Festa et al, in 2011, reported that adipocyte lineage cells support the stem cell niche and help drive the complex hair growth cycle. Adipose-derived regenerative cells (also known as stromal vascular fraction [SVF] is a heterogeneous group of noncultured cells that can be reliably extracted from adipose by using automated systems, and these cells work largely by paracrine mechanisms to support adipocyte viability. While, today, autologous fat is transplanted primarily for esthetic and reconstructive volume, surgeons have previously reported positive skin and hair changes posttransplantation. This follicular regenerative approach is intriguing and raises the possibility that one can drive or restore the hair cycle in male and female pattern baldness by stimulating the niche with autologous fat enriched with SVF. In this first of a kind patient series, the authors report on the safety, tolerability, and quantitative, as well as photographic changes, in a group of patients with early genetic alopecia treated with subcutaneous scalp injection of enriched adipose tissue. The findings suggest that scalp stem cell-enriched fat grafting may represent a promising alternative approach to

  7. The effect of adipose derived stromal vascular fraction on stasis zone in an experimental burn model.

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    Eyuboglu, Atilla Adnan; Uysal, Cagri A; Ozgun, Gonca; Coskun, Erhan; Markal Ertas, Nilgun; Haberal, Mehmet

    2018-03-01

    Stasis zone is the surrounding area of the coagulation zone which is an important part determining the extent of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Thermal injury was applied on dorsum of Sprague-Dawley rats (n=20) by the "comb burn" model as described previously. When the burn injury was established on Sprague-Dawley rats (30min); rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of Sprague-Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density, gradient of fibrosis and epithelial thickness were determined via immunohistochemical assay. Macroscopic stasis zone tissue viability (32±3.28%, 57±4.28%) (p51, 1.50±0.43) (pzone on acute burn injuries. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  8. Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy

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    Costa, M.; Cerqueira, Mariana Teixeira; Santos, T. C.; Marques, Belém Sampaio; Ludovico, Paula; Marques, A. P.; Pirraco, Rogério P.; Reis, R. L.

    2017-01-01

    Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditi...

  9. Wnt5a Regulates the Assembly of Human Adipose Derived Stromal Vascular Fraction-Derived Microvasculatures.

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    Venkat M Ramakrishnan

    Full Text Available Human adipose-derived stromal vascular fraction (hSVF cells are an easily accessible, heterogeneous cell system that can spontaneously self-assemble into functional microvasculatures in vivo. However, the mechanisms underlying vascular self-assembly and maturation are poorly understood, therefore we utilized an in vitro model to identify potential in vivo regulatory mechanisms. We utilized passage one (P1 hSVF because of the rapid UEA1+ endothelium (EC loss at even P2 culture. We exposed hSVF cells to a battery of angiogenesis inhibitors and found that the pan-Wnt inhibitor IWP2 produced the most significant hSVF-EC networking decrease (~25%. To determine which Wnt isoform(s and receptor(s may be involved, hSVF was screened by PCR for isoforms associated with angiogenesis, with only WNT5A and its receptor, FZD4, being expressed for all time points observed. Immunocytochemistry confirmed Wnt5a protein expression by hSVF. To see if Wnt5a alone could restore IWP2-induced EC network inhibition, recombinant human Wnt5a (0-150 ng/ml was added to IWP2-treated cultures. The addition of rhWnt5a significantly increased EC network area and significantly decreased the ratio of total EC network length to EC network area compared to untreated controls. To determine if Wnt5a mediates in vivo microvascular self-assembly, 3D hSVF constructs containing an IgG isotype control, anti-Wnt5a neutralizing antibody or rhWnt5a were implanted subcutaneously for 2w in immune compromised mice. Compared to IgG controls, anti-Wnt5a treatment significantly reduced vessel length density by ~41%, while rhWnt5a significantly increased vessel length density by ~62%. However, anti-Wnt5a or rhWnt5a did not significantly affect the density of segments and nodes, both of which measure vascular complexity. Taken together, this data demonstrates that endogenous Wnt5a produced by hSVF plays a regulatory role in microvascular self-assembly in vivo. These findings also suggest that

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

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    Ziqing Dong

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

  11. 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).

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    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.

  12. Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy.

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    Costa, Marina; Cerqueira, Mariana T; Santos, Tírcia C; Sampaio-Marques, Belém; Ludovico, Paula; Marques, Alexandra P; Pirraco, Rogério P; Reis, Rui L

    2017-06-01

    Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs. Neovascularization after implantation is a major obstacle for producing clinically viable cell sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic cell sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these cell sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb

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

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    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

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

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

    2017-09-01

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

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

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    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

  16. Viabilidade celular da fração mononuclear da medula óssea e fração vascular estromal do tecido adiposo de equinos após o processo de congelamento e descongelamento Viability of equine bone marrow mononuclear fraction and adipose tissue-derived stromal vascular fraction after freezing and thawing process

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    Gesiane Ribeiro

    2012-12-01

    Full Text Available Cinco cavalos adultos foram submetidos à coleta de medula óssea do esterno e de tecido adiposo da região glútea. As amostras foram processadas para obtenção da fração mononuclear da medula óssea e fração vascular estromal do tecido adiposo, o número de células obtidas e a viabilidade celular foram determinados. Em seguida, realizou-se o congelamento das amostras em solução contendo 20% de soro fetal bovino e 10% de dimetilsulfóxido. Depois de um mês, realizou-se o descongelamento das amostras e a viabilidade celular foi novamente mensurada. Os resultados revelaram que as técnicas utilizadas tanto para coleta de medula óssea quanto de tecido adiposo em equinos são simples, rápidas e seguras. As metodologias adotadas para o processamento das amostras foram eficientes, obtendo-se aproximadamente 95% de viabilidade celular. Após o descongelamento, a viabilidade média das amostras de células mononucleares da medula óssea foi de 86% e da fração vascular estromal do tecido adiposo de 64%. Frente à importância da terapia celular na clínica médica de equinos, concluiu-se que é necessária a realização de mais estudos, visando padronizar uma técnica de criopreservação que mantenha a integridade das células da fração mononuclear da medula óssea e da fração vascular estromal do tecido adiposo de equinos.In five adult horses, bone marrow was aspirated from the sternum and adipose tissue extracted from the gluteal region. The samples were processed to obtain the mononuclear fraction of bone marrow and stromal vascular fraction of adipose tissue, and the number of cells obtained and cell viability were determined. Next, the cell samples were frozen in medium containing 20% fetal bovine serum and 10% dimethylsulfoxide. After one month, the cells were thawed and cell viability was again determined. The results revealed that the techniques for collecting both bone marrow and adipose tissue in horses are simple, rapid and

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

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

    2017-01-01

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

  18. Effects of administration of adipose-derived stromal vascular fraction and platelet-rich plasma to dogs with osteoarthritis of the hip joints.

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    Upchurch, David A; Renberg, Walter C; Roush, James K; Milliken, George A; Weiss, Mark L

    2016-09-01

    OBJECTIVE To evaluate effects of simultaneous intra-articular and IV injection of autologous adipose-derived stromal vascular fraction (SVF) and platelet-rich plasma (PRP) to dogs with osteoarthritis of the hip joints. ANIMALS 22 client-owned dogs (12 placebo-treated [control] dogs and 10 treated dogs). PROCEDURES Dogs with osteoarthritis of the hip joints that caused signs of lameness or discomfort were characterized on the basis of results of orthopedic examination, goniometry, lameness score, the Canine Brief Pain Inventory (CBPI), a visual analogue scale, and results obtained by use of a pressure-sensing walkway at week 0 (baseline). Dogs received a simultaneous intraarticular and IV injection of SVF and PRP or a placebo. Dogs were examined again 4, 8, 12, and 24 weeks after injection. RESULTS CBPI scores were significantly lower for the treatment group at week 24, compared with scores for the control group. Mean visual analogue scale score for the treatment group was significantly higher at week 0 than at weeks 4, 8, or 24. Dogs with baseline peak vertical force (PVF) in the lowest 25th percentile were compared, and the treatment group had a significantly higher PVF than did the control group. After the SVF-PRP injection, fewer dogs in the treated group than in the control group had lameness confirmed during examination. CONCLUSIONS AND CLINICAL RELEVANCE For dogs with osteoarthritis of the hip joints treated with SVF and PRP, improvements in CBPI and PVF were evident at some time points, compared with results for the control group.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  20. First-in-man intraglandular implantation of stromal vascular fraction and adipose-derived stem cells plus platelet-rich plasma in irradiation-induced gland damage: a case study

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    Comella K

    2017-08-01

    Full Text Available Kristin Comella,1 Walter Bell2 1US Stem Cell, Inc, Sunrise, FL, USA; 2South African Stem Cell Institute, Parys, South Africa Background: Stromal vascular fraction (SVF is a mixture of cells which can be isolated from a mini-lipoaspirate of fat tissue. Platelet-rich plasma (PRP is a mixture of growth factors and other nutrients which can be obtained from peripheral blood. Adipose-derived stem/stromal cells (ADSCs can be isolated from fat tissue and expanded in culture. The SVF includes a variety of different cells such as ADSCs, pericytes, endothelial/progenitor cells, and a mix of different growth factors. The adipocytes (fat cells can be removed via centrifugation. Here, we describe the rationale and, to our knowledge, the first clinical implementation of SVF and PRP followed by repeat dosing of culture-expanded ADSCs into a patient with severe xerostomia postirradiation. Methods: Approximately 120 mLs of adipose tissue was removed via mini-lipoaspirate procedure under local anesthetic. The SVF was prepared from half of the fat and resuspended in PRP. The mixture was delivered via ultrasound directly into the submandibular and parotid glands on both the right and left sides. The remaining 60 mLs of fat was processed to culture-expand ADSCs. The patient received seven follow-up injections of the ADSCs plus PRP at 5, 8, 16, 18, 23, 28, and 31 months postliposuction. The subject was monitored over a period of 31 months for safety (adverse events, glandular size via ultrasound and saliva production. Results: Throughout the 31-month monitoring period, no safety events such as infection or severe adverse events were reported. The patient demonstrated an increase in gland size as measured by ultrasound which corresponded to increased saliva production. Conclusion: Overall, the patient reported improved quality of life and willingness to continue treatments. The strong safety profile and preliminary efficacy results warrant larger studies to determine

  1. 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

  2. Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

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    Mingliang Sun

    2017-01-01

    Full Text Available Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF, basic fibroblast growth factor (bFGF, and monocyte chemotactic protein-1 (MCP-1 in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.

  3. Expanded Stem Cells, Stromal-Vascular Fraction, and Platelet-Rich Plasma Enriched Fat: Comparing Results of Different Facial Rejuvenation Approaches in a Clinical Trial.

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    Rigotti, Gino; Charles-de-Sá, Luiz; Gontijo-de-Amorim, Natale Ferreira; Takiya, Christina Maeda; Amable, Paola Romina; Borojevic, Radovan; Benati, Donatella; Bernardi, Paolo; Sbarbati, Andrea

    2016-03-01

    In a previous study, the authors demonstrated that treatment with expanded adipose-derived stem cells or stromal vascular fraction (SVF)-enriched fat modify the pattern of the dermis in human beings, representing a skin rejuvenation effect. Considering that expanded stem cells require a cell factor, the authors wanted to assess similar results by replacing them with platelet-rich plasma (PRP), which is easier to obtain and for which an empirical regenerative effect has been already described. To determine if PRP injection could replace the cutaneous regenerative effect of adipose-derived stem cells. This study was performed in 13 patients who were candidates for facelift. The patients underwent sampling of fat by liposuction from the abdomen and submitted to one of three protocols: injection of SVF-enriched fat or expanded adipose-derived stem cells or fat plus PRP in the preauricular areas. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. The use of fat plus PRP led to the presence of more pronounced inflammatory infiltrates and a greater vascular reactivity, increasing in vascular permeability and a certain reactivity of the nervous component. The addition of PRP did not improve the regenerative effect. The use of PRP did not have significant advantages in skin rejuvenation over the use of expanded adipose-derived stem cells or SVF-enriched fat. The effect of increased vascular reactivity may be useful in pathological situations in which an intense angiogenesis is desirable, such as tissular ischemia. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Blaber Sinead P

    2012-08-01

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

  5. CD54+ rabbit adipose-derived stem cells overexpressing HIF-1α facilitate vascularized fat flap regeneration

    Science.gov (United States)

    Liang, Zhi-Jie; Huang, Min-Hong; Peng, Qi-Liu; Zou, Dong-Hua; Gu, Rong-He; Xu, Fang-Tian; Gao, Hui; Chen, Zhen-Dong; Chi, Guang-Yi; Wei, Zhong-Heng; Chen, Li; Li, Hong-Mian

    2017-01-01

    Fat flap transplantation is frequently performed in patients suffering from soft tissue defects resulting from disease or trauma. This study explored the feasibility of constructing vascularized fat flaps using rabbit adipose-derived stem cells (rASCs) and collagen scaffolds in a rabbit model. We evaluated rASCs proliferation, paracrine function, adipogenesis, vascularization, and CD54 expression, with or without HIF-1α transfection in vitro and in vivo. We observed that adipogenic differentiation potential was greater in rASCs with high CD54 expression (CD54+rASCs) than in those with low expression (CD54–rASCs), both in vitro and in vivo. HIF-1α overexpression not only augmented this effect, but also enhanced cell proliferation and paracrine function in vitro. We also demonstrated that HIF-1α-transfected CD54+rASCs showed enhanced paracrine function and adipogenic capacity, and that paracrine function increases expression of angiogenesis-related markers. Thus, CD54+rASCs overexpressing HIF-1α enhanced large volume vascularized fat flap regeneration in rabbits, suggesting CD54 may be an ideal candidate marker for ASCs adipogenic differentiation. PMID:28423354

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Fodor, Peter B; Paulseth, Stephen G

    2016-02-01

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

  8. Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

    Science.gov (United States)

    Ishii, Makoto; Iadecola, Costantino

    2016-05-01

    Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial.

    Science.gov (United States)

    Granel, Brigitte; Daumas, Aurélie; Jouve, Elisabeth; Harlé, Jean-Robert; Nguyen, Pierre-Sébastien; Chabannon, Christian; Colavolpe, Nathalie; Reynier, Jean-Charles; Truillet, Romain; Mallet, Stéphanie; Baiada, Antoine; Casanova, Dominique; Giraudo, Laurent; Arnaud, Laurent; Veran, Julie; Sabatier, Florence; Magalon, Guy

    2015-12-01

    In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. GFRS (Groupe Francophone de Recherche sur la Sclérodermie). NCT01813279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

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

    Science.gov (United States)

    2011-01-01

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

  11. Adipose-derived mesenchymal stem cells and regenerative medicine.

    Science.gov (United States)

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

    2013-04-01

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

  12. The influence of perivascular adipose tissue on vascular homeostasis.

    Science.gov (United States)

    Szasz, Theodora; Bomfim, Gisele Facholi; Webb, R Clinton

    2013-01-01

    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.

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

    Science.gov (United States)

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

    2008-09-01

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

  14. First-in-man intravenous implantation of stromal vascular fraction in psoriasis: a case study.

    Science.gov (United States)

    Comella, Kristin; Parlo, Michelle; Daly, Rosemary; Dominessy, Kellie

    2018-01-01

    Stromal vascular fraction (SVF) is a mixture of adipose-derived stem cells/mesenchymal stem cells, endothelial/progenitors, pericytes, fibroblasts, and other cells obtained from fat tissue. A small sample of fat or adipose tissue can be obtained under local anesthesia using a cannula. After an enzymatic digestion and centrifugation, the adipocytes (fat cells) are removed to obtain an SVF. Here, we describe the rationale and, to our knowledge, the first clinical implementation of SVF intravenously in a patient with severe psoriasis. Adipose tissue (60 mL) was collected under local anesthesia via a mini-lipoaspirate procedure. The SVF was separated from the adipocytes via centrifugation after an enzymatic digestion. The cells were resuspended in normal saline and injected via bolus push intravenous. The subject was monitored over a period of 12 months for safety (adverse events), medication changes, and quality of life parameters. The patient did not report any safety concerns and did not experience any severe adverse events. The patient demonstrated a significant decrease in symptoms with a noticeable difference in skin quality appearance. Psoriasis area and severity index score went from 50.4 at baseline to 0.3 at 1 month follow-up. Overall, the patient reported improved quality of life and willingness to continue treatments. This successful initial case study demonstrates that this may be a feasible treatment plan for patients suffering from psoriasis.

  15. Non-cultured adipose-derived CD45(-) side population cells are enriched for progenitors that give rise to myofibres in vivo

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Schrøder, Henrik D; Jensen, Charlotte H

    2008-01-01

    Side population (SP) cells are highly able to exclude the Hoechst 33342 dye through membrane transporters, a feature associated with cell immaturity and therefore proposed as a marker of stem cells. Herein we demonstrate that the adipose tissue derived stromal vascular fraction (SVF) contains...... skeletal muscle repair mainly relies on the satellitecell, several reports have shown that vessel-associated cells may adopt a myogenic phenotype when exposed to a muscle environment. In accordance with these findings, we also observed invitro myogenic specification of SPCD45(-) cells when cocultured...... a novel population of non-haematopoietic "side population" (SPCD45(-)) cells. Simultaneous qRT-PCR of 64 genes revealed that the freshly isolated SPCD45(-) was highly enriched for cells expressing genes related to stem cells, the Notch pathway, and early vascular precursors. Notably, the expression...

  16. Stromal vascular fraction isolated from lipo-aspirates using an automated processing system: bench and bed analysis.

    Science.gov (United States)

    Doi, Kentaro; Tanaka, Shinsuke; Iida, Hideo; Eto, Hitomi; Kato, Harunosuke; Aoi, Noriyuki; Kuno, Shinichiro; Hirohi, Toshitsugu; Yoshimura, Kotaro

    2013-11-01

    The heterogeneous stromal vascular fraction (SVF), containing adipose-derived stem/progenitor cells (ASCs), can be easily isolated through enzymatic digestion of aspirated adipose tissue. In clinical settings, however, strict control of technical procedures according to standard operating procedures and validation of cell-processing conditions are required. Therefore, we evaluated the efficiency and reliability of an automated system for SVF isolation from adipose tissue. SVF cells, freshly isolated using the automated procedure, showed comparable number and viability to those from manual isolation. Flow cytometric analysis confirmed an SVF cell composition profile similar to that after manual isolation. In addition, the ASC yield after 1 week in culture was also not significantly different between the two groups. Our clinical study, in which SVF cells isolated with the automated system were transplanted with aspirated fat tissue for soft tissue augmentation/reconstruction in 42 patients, showed satisfactory outcomes with no serious side-effects. Taken together, our results suggested that the automated isolation system is as reliable a method as manual isolation and may also be useful in clinical settings. Automated isolation is expected to enable cell-based clinical trials in small facilities with an aseptic room, without the necessity of a good manufacturing practice-level cell processing area. Copyright © 2012 John Wiley & Sons, Ltd.

  17. 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

  18. Myocardial regeneration potential of adipose tissue-derived stem cells

    International Nuclear Information System (INIS)

    Bai, Xiaowen; Alt, Eckhard

    2010-01-01

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

  19. Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

    Directory of Open Access Journals (Sweden)

    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.

  20. Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model.

    Science.gov (United States)

    Ismail, Tarek; Osinga, Rik; Todorov, Atanas; Haumer, Alexander; Tchang, Laurent A; Epple, Christian; Allafi, Nima; Menzi, Nadia; Largo, René D; Kaempfen, Alexandre; Martin, Ivan; Schaefer, Dirk J; Scherberich, Arnaud

    2017-11-01

    Avascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. The standard of care, vascularized bone grafts, is limited by donor site morbidity and restricted availability. The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes in a rat model of AVN. SVF cells were isolated from lipoaspirates and cultured onto porous hydroxyapatite scaffolds within a perfusion-based bioreactor system for 5days. The resulting constructs were inserted into devitalized bone cylinders mimicking AVN-affected bone. A ligated vascular bundle was inserted upon subcutaneous implantation of constructs in nude rats. After 1 and 8weeks in vivo, bone formation and vascularization were analyzed. Newly-formed bone was found in 80% of SVF-seeded scaffolds after 8weeks but not in unseeded controls. Human ALU+cells in the bone structures evidenced a direct contribution of SVF cells to bone formation. A higher density of regenerative, M2 macrophages was observed in SVF-seeded constructs. In both experimental groups, devitalized bone was revitalized by vascularized tissue after 8 weeks. SVF cells-based osteogenic constructs revitalized fully necrotic bone in a challenging AVN rat model of clinically-relevant size. SVF cells contributed to accelerated initial vascularization, to bone formation and to recruitment of pro-regenerative endogenous cells. Avascular necrosis (AVN) of bone often requires surgical treatment with autologous bone grafts, which is surgically demanding and restricted by significant donor site morbidity and limited availability. This paper describes a de novo engineered axially-vascularized bone graft substitute and tests the potential to revitalize dead bone and provide efficient new bone formation in a rat model. The engineering of an osteogenic/vasculogenic construct of clinically-relevant size with stromal vascular fraction of human adipose, combined to an arteriovenous bundle is described. This

  1. 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.

  2. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase

    Directory of Open Access Journals (Sweden)

    Silvia Baldari

    2016-07-01

    Full Text Available Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs, suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2. Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.

  5. Characterization Of Bovine Adipose-Derived Stem Cells

    OpenAIRE

    Daniel Cebo

    2017-01-01

    Bovine adipose-derived stem cells were obtained from the subcutaneous abdominal adipose tissue. The cells were cultured by the modified tissue-explants method developed in our laboratory and then analyzed using optical microscopy and flow cytometry. These cells were able to replicate in our cell culture conditions. cell Flow cytometry showed that bovine adipose-derived stem cells expressed mesenchymal stem cell markers CD73 and CD90. Meanwhile haematopoietic markers CD45 and CD34 are absent f...

  6. In vitro assessment of cytotoxicity and labeling efficiency of 99mTc-HMPAO with stromal vascular fraction of adipose tissue

    International Nuclear Information System (INIS)

    Verma, V.K.; Beevi, S.S.; Tabassum, A.; Kumaresan, K.; Kamaraju, R.S.; Arbab, A.S.; Chelluri, L.K.

    2014-01-01

    Introduction: Noninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of 99m Tc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy. Methods: Ten million cells of SVF were labeled with 99m Tc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of 99m Tc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H 2 DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1. Results: An encouraging labeling efficiency of 33% was observed with 99m Tc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays. Conclusion: 99m Tc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with 99m Tc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy

  7. Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells

    DEFF Research Database (Denmark)

    Tratwal, Josefine; Mathiasen, Anders Bruun; Juhl, Morten

    2015-01-01

    INTRODUCTION: Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF...... stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns...... of ASCs. METHODS: Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow...

  8. Combined therapy for critical limb ischemia: biomimetic PLGA microcarriers potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction cells.

    Science.gov (United States)

    Hoareau, Laurence; Fouchet, Florian; Planesse, Cynthia; Mirbeau, Sophie; Sindji, Laurence; Delay, Emmanuel; Roche, Régis; Montero-Menei, Claudia N; Festy, Franck

    2018-04-14

    We propose a regenerative solution in the treatment of critical limb ischemia. Poly-lactic/glycolic acid (PLGA) microcarriers were prepared and coated with laminin to be sterilized through γ-irradiation of 25 kGy at low temperature. Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion of adipose tissue. Streptozotocin-induced diabetic mice underwent arteriotomy and received an administration of SVF cells combined or not with biomimetic microcarriers. Functional evaluation of the ischemic limb was then reported and tissue reperfusion was evaluated through fluorescence molecular tomography (FMT). Microcarriers were stable and functional after γ-irradiation until at least 12 months storage. Mice which received an injection of SVF cells in the ischemic limb have 22 % of supplementary blood supply within this limb 7 days after surgery compared to vehicle, whereas no difference was observed at day 14. With the combined therapy, the improvement of blood flow is significantly higher compared to vehicle, of about 31 % at day 7 and of about 11 % at day 14. Injection of SVF cells induces a significant 27 % decrease of necrosis compared to vehicle. This effect is more important when SVF cells were mixed with biomimetic microcarriers: - 37% compared to control. Although SVF cells injection leads to a non-significant 22 % proprioception recovery, the combined therapy induces a significant recovery of about 27 % compared to vehicle. We show that the combination of SVF cells from adipose tissue with laminin-coated PLGA microcarriers is efficient for CLI therapy in a diabetic mouse model. This article is protected by copyright. All rights reserved.

  9. Adipose stem cells for bone tissue repair

    OpenAIRE

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

    2017-01-01

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

  10. Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-2-0042 TITLE: Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite...2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Adult Tissue-Derived Stem Cells and Tolerance Induction...Distribution Unlimited 13. SUPPLEMENTARY NOTES The utilization of adult derived adipose stem cells administration in composite tissue transplantation

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

    Science.gov (United States)

    2012-05-10

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

  12. Triactome: neuro-immune-adipose interactions. Implication in vascular biology

    Directory of Open Access Journals (Sweden)

    George Nikov Chaldakov

    2014-04-01

    Full Text Available Understanding how the precise interactions of nerves, immune cells and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae: intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue, we recently designated tunica adiposa (in brief, adiposa like intima, media, adventitia. According to present paradigm, atherosclerosis is an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. Periadventitial adipose tissue expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic signaling proteins collectively dubbed adipokines. However, the role of perivascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

  13. Enhanced mitogenesis in stromal vascular cells derived from subcutaneous adipose tissue of Wagyu compared with those of Angus cattle.

    Science.gov (United States)

    Wei, S; Fu, X; Liang, X; Zhu, M J; Jiang, Z; Parish, S M; Dodson, M V; Zan, L; Du, M

    2015-03-01

    Japanese Wagyu cattle are well known for their extremely high marbling and lower subcutaneous adipose tissue compared with Angus cattle. However, mechanisms for differences in adipose deposition are unknown. The objective of this paper was to evaluate breed differences in the structure of subcutaneous adipose tissue, adipogenesis, and mitogenesis of stromal vascular (SV) cells between Wagyu and Angus cattle. Subcutaneous biopsy samples were obtained from 5 Wagyu (BW = 302 ± 9 kg) and 5 Angus (BW = 398 ± 12 kg) heifers at 12 mo of age, and samples were divided into 3 pieces for histological examination, biochemical analysis, and harvest of SV cells. Adipogenesis of SV cells was assessed by the expression of adipogenic markers and Oil Red-O staining, while mitogenesis was evaluated by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium dromide) test, phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB; AKT). Based on histological analysis, Wagyu had larger adipocytes compared with Angus. At the tissue level, protein expression of peroxisome proliferator-activated receptor γ (PPARG) in Wagyu was much lower compared with that of Angus. Similarly, a lower mRNA expression of PPARG was found in Wagyu SV cells. No significant difference was observed for the zinc finger protein 423 (ZNF423) expression between Wagyu and Angus. As assessed by Oil Red-O staining, Wagyu SV cells possessed a notable trend of lower adipogenic capability. Interestingly, higher mitogenic ability was discovered in Wagyu SV cells, which was associated with an elevated phosphorylation of ERK1/2. There was no difference in AKT phosphorylation of SV cells between Wagyu and Angus. Moreover, exogenous fibroblast growth factor 2 (FGF2) enhanced mitogenesis and ERK1/2 phosphorylation of SV cells to a greater degree in Angus compared with that in Wagyu. Expression of transforming growth factor β 3 (TGFB3) and bone morphogenetic protein 2 (BMP2) in Wagyu SV

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

    Directory of Open Access Journals (Sweden)

    Thomas A Mendel

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

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

    Directory of Open Access Journals (Sweden)

    Feisst V

    2015-11-01

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

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

    OpenAIRE

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

    2012-01-01

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

  17. In vitro assessment of cytotoxicity and labeling efficiency of {sup 99m}Tc-HMPAO with stromal vascular fraction of adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Verma, V. K.; Beevi, S. S. [Department of Transplant Biology, Immunology and Stem Cell Lab, Global Hospitals, Hyderabad (India); Tabassum, A.; Kumaresan, K. [KK Nuclear Scans, Raj Bhavan Road, Somajiguda, Hyderabad (India); Kamaraju, R. S. [Department of Transplant Biology, Immunology and Stem Cell Lab, Global Hospitals, Hyderabad (India); Arbab, A. S. [Cancer Centre, GA Regents University, Augusta, GA (United States); Chelluri, L.K., E-mail: lkiran@globalhospitalsindia.com [Department of Transplant Biology, Immunology and Stem Cell Lab, Global Hospitals, Hyderabad (India)

    2014-10-15

    Introduction: Noninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of {sup 99m}Tc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy. Methods: Ten million cells of SVF were labeled with {sup 99m}Tc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of {sup 99m}Tc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H{sub 2}DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1. Results: An encouraging labeling efficiency of 33% was observed with {sup 99m}Tc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays. Conclusion: {sup 99m}Tc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with {sup 99m}Tc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy.

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

    Science.gov (United States)

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

    2018-05-26

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

  19. Promotion of Vascular Morphogenesis of Endothelial Cells Co-Cultured with Human Adipose-Derived Mesenchymal Stem Cells Using Polycaprolactone/Gelatin Nanofibrous Scaffolds

    Directory of Open Access Journals (Sweden)

    Yun-Min Kook

    2018-02-01

    Full Text Available New blood vessel formation is essential for tissue regeneration to deliver oxygen and nutrients and to maintain tissue metabolism. In the field of tissue engineering, in vitro fabrication of new artificial vessels has been a longstanding challenge. Here we developed a technique to reconstruct a microvascular system using a polycaprolactone (PCL/gelatin nanofibrous structure and a co-culture system. Using a simple electrospinning process, we fabricated three-dimensional mesh scaffolds to support the sprouting of human umbilical vein endothelial cells (HUVECs along the electrospun nanofiber. The co-culture with adipose-derived mesenchymal stem cells (ADSCs supported greater sprouting of endothelial cells (ECs. In a two-dimensional culture system, angiogenic cell assembly produced more effective direct intercellular interactions and paracrine signaling from ADSCs to assist in the vascular formation of ECs, compared to the influence of growth factor. Although vascular endothelial growth factor and sphingosine-1-phosphate were present during the culture period, the presence of ADSCs was the most important factor for the construction of a cell-assembled structure in the two-dimensional culture system. On the contrary, HUVECs co-cultured on PCL/gelatin nanofiber scaffolds produced mature and functional microvessel and luminal structures with a greater expression of vascular markers, including platelet endothelial cell adhesion molecule-1 and podocalyxin. Furthermore, both angiogenic factors and cellular interactions with ADSCs through direct contact and paracrine molecules contributed to the formation of enhanced engineered blood vessel structures. It is expected that the co-culture system of HUVECs and ADSCs on bioengineered PCL/gelatin nanofibrous scaffolds will promote robust and functional microvessel structures and will be valuable for the regeneration of tissue with restored blood vessels.

  20. 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....

  1. 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.

  2. Adipose-Derived Stem Cells and Application Areas

    Directory of Open Access Journals (Sweden)

    Mujde Kivanc

    2015-09-01

    Full Text Available The use of stem cells derived from adipose tissue as an autologous and self-replenishing source for a variety of differentiated cell phenotypes, provides a great deal of promise for reconstructive surgery. The secret of the human body, stem cells are reserved. Stem cells are undifferentiated cells found in the human body placed in any body tissue characteristics that differentiate and win ever known to cross the tissue instead of more than 200 diseases and thus improve and, rejuvenates the tissues. So far, the cord blood of newborn babies are used as a source of stem cells, bone marrow, and twenty years after tooth stem cells in human adipose tissue, scientists studied more than other sources of stem cells in adipose tissue and discovered that. Increase in number of in vitro studies on adult stem cells, depending on many variables is that the stem cells directly to the desired soybean optimization can be performed.. We will conclude by assessing potential avenues for developing this incredibly promising field. The aim of this paper is to review the existing literature on applications of harvest, purification, characterization and cryopreservation of adipose-derived stem cells (ASCs. [Cukurova Med J 2015; 40(3.000: 399-408

  3. Epigenetic programming of adipose-derived stem cells in low birthweight individuals

    DEFF Research Database (Denmark)

    Broholm, Christa; Olsson, Anders H; Perfilyev, Alexander

    2016-01-01

    Aims/hypothesis: Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction...

  4. Hypoxia induced VEGF synthesis in visceral adipose depots of obese diabetic patients.

    Science.gov (United States)

    Fusaru, Ana Marina; Pisoschi, Cătălina Gabriela; Bold, Adriana; Taisescu, C; Stănescu, R; Hîncu, Mihaela; Crăiţoiu, Stefania; Baniţă, Ileana Monica

    2012-01-01

    VEGF is one the pro-inflammatory adipokines synthesized by the "adipose secretoma" of obese subjects as a response to hypoxic conditions; but the main function of VEGF is angiogenesis, being recognized as the most important factor increasing blood capillaries in the adipose tissue by stimulating endothelial cell growth. In this paper, we propose a comparative study of the vascular response to VEGF synthesis in the subcutaneous and central-peritoneal adipose depots in lean, obese and obese diabetic patients. We used CD31 to label the endothelial cells in order to evaluate the response of the vascular network to VEGF synthesis. Our results showed an increase of VEGF protein synthesis in obese and obese-diabetic patients compared to lean subjects where the protein was absent. The positivity for VEGF in obese diabetic samples was observed in numerous structures from the adipose depots, both in the stromal vascular fraction--blood vessels and stromal cells--as well as in the cytoplasm of adipocytes. Positivity in the vascular wall was observed more frequently in areas of perivascular and intralobular fibrosis. Obese and diabetic patients showed similar incidence of CD31 immunoreactivity with lean subjects in both subcutaneous and peritoneal depots. In conclusion, human adipose depots show a different incidence of VEGF positive cells in relation with their disposal and the metabolic status. VEGF synthesis in visceral adipose tissue is inefficient being not followed by angiogenesis to counterbalance tissue hypoxia. We suggest that may be a pathogenic link between the degrees of intralobular fibrosis in adipose depots and VEGF expression.

  5. Progranulin, a major secreted protein of mouse adipose-derived stem cells, inhibits light-induced retinal degeneration.

    Science.gov (United States)

    Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tomohiro; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru; Hara, Hideaki

    2014-01-01

    Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina.

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

    African Journals Online (AJOL)

    Jane

    2011-10-10

    Oct 10, 2011 ... stem cells (ADSCs) may play an important role in this field. In this research ..... Adipose tissue is derived from embryonic mesodermal precursors and .... Clonogenic multipotent stem cells in human adipose tissue differentiate ...

  7. Adipose Derived Mesenchymal Stem Cells In Wound Healing: A Clinical Review

    Directory of Open Access Journals (Sweden)

    Gunalp Uzun

    2014-08-01

    Full Text Available The aim of this article is to review clinical studies on the use of adipose derived mesenchymal stem cells in the treatment of chronic wounds. A search on PubMed was performed on April 30th, 2014 to identify the relevant clinical studies. We reviewed 13 articles that reported the use adipose derived stem cells in the treatment of different types of wounds. Adipose derived stem cells have the potential to be used in the treatment of chronic wounds. However, standard methods for isolation, storage and application of these cells are needed. New materials to transfer these stem cells to injured tissues should be investigated. [Dis Mol Med 2014; 2(4.000: 57-64

  8. Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Galbo, H

    2012-01-01

    Objective:The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM).Design:Clinical intervention study with 1-h intravenous adrenaline infusion.Subjects:Eight male overweight T2DM subjects...... and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging...... infusion. One hour post adrenaline, ATBF was still increased in overweight T2DM subjects. Adrenaline increased microvascular volume in non-T2DM subjects while this response was impaired in overweight T2DM subjects. Adrenaline-induced increase in lipolysis was similar in both groups, but NEFA output from...

  9. Adipose-Derived Stem Cells Promote Peripheral Nerve Regeneration In Vivo without Differentiation into Schwann-Like Lineage.

    Science.gov (United States)

    Sowa, Yoshihiro; Kishida, Tsunao; Imura, Tetsuya; Numajiri, Toshiaki; Nishino, Kenichi; Tabata, Yasuhiko; Mazda, Osam

    2016-02-01

    During recent decades, multipotent stem cells were found to reside in the adipose tissue, and these adipose-derived stem cells were shown to play beneficial roles, like those of Schwann cells, in peripheral nerve regeneration. However, it has not been well established whether adipose-derived stem cells offer beneficial effects to peripheral nerve injuries in vivo as Schwann cells do. Furthermore, the in situ survival and differentiation of adipose-derived stem cells after transplantation at the injured peripheral nerve tissue remain to be fully elucidated. Adipose-derived stem cells and Schwann cells were transplanted with gelatin hydrogel tubes at the artificially blunted sciatic nerve lesion in mice. Neuroregenerative abilities of them were comparably estimated. Cre-loxP-mediated fate tracking was performed to visualize survival in vivo of transplanted adipose-derived stem cells and to investigate whether they differentiated into Schwann linage cells at the peripheral nerve injury site. The transplantation of adipose-derived stem cells promoted regeneration of axons, formation of myelin, and restoration of denervation muscle atrophy to levels comparable to those achieved by Schwann cell transplantation. The adipose-derived stem cells survived for at least 4 weeks after transplantation without differentiating into Schwann cells. Transplanted adipose-derived stem cells did not differentiate into Schwann cells but promoted peripheral nerve regeneration at the injured site. The neuroregenerative ability was comparable to that of Schwann cells. Adipose-derived stem cells at an undifferentiated stage may be used as an alternative cell source for autologous cell therapy for patients with peripheral nerve injury.

  10. Isolation and expansion of adipose-derived stem cells for tissue engineering

    DEFF Research Database (Denmark)

    Fink, Trine; Rasmussen, Jeppe Grøndahl; Lund, Pia

    2011-01-01

    For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs for subseq......For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs...

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

    Directory of Open Access Journals (Sweden)

    Qin JB

    2012-10-01

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

  12. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

    2014-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

  13. 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.

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

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    Fang Wang

    2018-02-01

    Full Text Available 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 < 0.01. Cells differentiated in 5% oxygen conditions showed greater contraction effect (p < 0.01. Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

  15. Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Campioli, Enrico [Research Institute of the McGill University Health Centre (Canada); Department of Medicine, McGill University, Montréal, Québec (Canada); Duong, Tam B. [Research Institute of the McGill University Health Centre (Canada); Deschamps, François [Synthèse AptoChem Inc., Montréal, Québec (Canada); Papadopoulos, Vassilios, E-mail: vassilios.papadopoulos@mcgill.ca [Research Institute of the McGill University Health Centre (Canada); Department of Medicine, McGill University, Montréal, Québec (Canada); Department of Biochemistry, McGill University, Montréal, Québec (Canada); Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec (Canada)

    2015-07-15

    Plastics are generally mixed with additives like plasticizers to enhance their flexibility, pliability, and elasticity proprieties. Plasticizers are easily released into the environment and are absorbed mainly through ingestion, dermal contact, and inhalation. One of the main classes of plasticizers, phthalates, has been associated with endocrine and reproductive diseases. In 2002, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced in the market for use in plastic materials and articles intended to come into contact with food, and it received final approval from the European Food Safety Authority in 2006. At present, there is limited knowledge about the safety and potential metabolic and endocrine-disrupting properties of DINCH and its metabolites. The purpose of this study was to evaluate the biological effects of DINCH and its active metabolites, cyclohexane-1,2-dicarboxylic acid (CHDA) and cyclohexane-1,2-dicarboxylic acid mono isononyl ester (MINCH), on rat primary stromal vascular fraction (SVF) of adipose tissue. DINCH and its metabolite, CHDA, were not able to directly affect SVF differentiation. However, exposure of SVF to 50 μM and 100 μM concentrations of MINCH affected the expression of Cebpa and Fabp4, thus inducing SVF preadipocytes to accumulate lipids and fully differentiate into mature adipocytes. The effect of MINCH was blocked by the specific peroxisome proliferator-activated receptor (PPAR)-α antagonist, GW6471. Taken together, these results suggest that MINCH is a potent PPAR-α agonist and a metabolic disruptor, capable of inducing SVF preadipocyte differentiation, that may interfere with the endocrine system in mammals. - Highlights: • DINCH and CHDA did not affect the adipogenesis of the SVF. • MINCH affected the adipogenesis of the SVF. • MINCH effect was blocked by the specific PPAR-α antagonist GW6471. • MINCH exerted a similar effect as MEHP on SVF adipogenesis. • DINCH/MINCH are potential metabolic

  16. Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation and polarization in type 2 diabetic ApoE-/- mouse.

    Science.gov (United States)

    Liu, Ming-Hao; Li, Ya; Han, Lu; Zhang, Yao-Yuan; Wang, Di; Wang, Zhi-Hao; Zhou, Hui-Min; Song, Ming; Li, Yi-Hui; Tang, Meng-Xiong; Zhang, Wei; Zhong, Ming

    2017-07-01

    Atherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4 + T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4 + T cells as well. Whether T2DM ADSCs are impaired in antagonizing CD4 + T cell proliferation and polarization remains unclear. We constructed type 2 diabetic ApoE -/- mouse models and tested infiltration and subgroups of CD4 + T cell in stromal-vascular fraction (SVF) in vivo. Normal/T2DM ADSCs and normal splenocytes with or without CD4 sorting were separated and co-cultured at different scales ex vivo. Immune phenotypes of pro- and anti-inflammation of ADSCs were also investigated. Flow cytometry (FCM) and ELISA were applied in the experiments above. CD4 + T cells performed a more pro-inflammatory phenotype in adipose tissue in T2DM ApoE -/- mice in vivo. Restriction to CD4 + T cell proliferation and polarization was manifested obviously weakened after co-cultured with T2DM ADSCs ex vivo. No obvious distinctions were found in morphology and growth type of both ADSCs. However, T2DM ADSCs acquired a pro-inflammatory immune phenotype, with secreting less PGE2 and expressing higher MHC-II and co-stimulatory molecules (CD40, CD80). Normal ADSCs could also obtain the phenotypic change after cultured with T2DM SVF supernatant. CD4 + T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabetic ApoE -/- mice. T2DM ADSCs had impaired function in restricting CD4 + T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The Effect of Conditioned Media of Adipose-Derived Stem Cells on Wound Healing after Ablative Fractional Carbon Dioxide Laser Resurfacing

    Science.gov (United States)

    Zhou, Bing-Rong; Xu, Yang; Guo, Shi-Lei; Xu, Yan; Wang, Ying; Zhu, Fen; Wu, Di; Yin, Zhi-Qiang; Luo, Dan

    2013-01-01

    Objective. To evaluate the benefits of conditioned medium of Adipose-derived stem cells (ADSC-CM) on wound healing after fractional carbon dioxide laser resurfacing (FxCR) on human skin. Materials and Methods. Nineteen subjects were treated with FxCR on the bilateral inner arms. ADSC-CM was applied on FxCR site of one randomly selected arm. Transepidermal water loss (TEWL), skin color, and gross-elasticity of FxCR site on both arms were measured. Skin samples were taken by biopsy from three subjects 3 weeks after treatment for histopathological manifestations and mRNA expressions of procollagen types I and III, elastin genes were noted. Results. The index of erythema, melanin, and TEWL of the ADSC-CM-treated skin were significantly lower than those of the control side. The mRNA expression of type III procollagen in ADSC-CM-treated group at 3 weeks posttreatment was 2.6 times of that of the control group. Conclusion. Application of allograft ADSC-CM is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL. PMID:24381938

  18. The Effect of Conditioned Media of Adipose-Derived Stem Cells on Wound Healing after Ablative Fractional Carbon Dioxide Laser Resurfacing

    Directory of Open Access Journals (Sweden)

    Bing-Rong Zhou

    2013-01-01

    Full Text Available Objective. To evaluate the benefits of conditioned medium of Adipose-derived stem cells (ADSC-CM on wound healing after fractional carbon dioxide laser resurfacing (FxCR on human skin. Materials and Methods. Nineteen subjects were treated with FxCR on the bilateral inner arms. ADSC-CM was applied on FxCR site of one randomly selected arm. Transepidermal water loss (TEWL, skin color, and gross-elasticity of FxCR site on both arms were measured. Skin samples were taken by biopsy from three subjects 3 weeks after treatment for histopathological manifestations and mRNA expressions of procollagen types I and III, elastin genes were noted. Results. The index of erythema, melanin, and TEWL of the ADSC-CM-treated skin were significantly lower than those of the control side. The mRNA expression of type III procollagen in ADSC-CM-treated group at 3 weeks posttreatment was 2.6 times of that of the control group. Conclusion. Application of allograft ADSC-CM is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.

  19. Enrichment of Adipose-Derived Stromal Cells for BMPR1A Facilitates Enhanced Adipogenesis.

    Science.gov (United States)

    Zielins, Elizabeth R; Paik, Kevin; Ransom, Ryan C; Brett, Elizabeth A; Blackshear, Charles P; Luan, Anna; Walmsley, Graham G; Atashroo, David A; Senarath-Yapa, Kshemendra; Momeni, Arash; Rennert, Robert; Sorkin, Michael; Seo, Eun Young; Chan, Charles K; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

    2016-02-01

    Reconstruction of soft tissue defects has traditionally relied on the use of grafts and flaps, which may be associated with variable resorption and/or significant donor site morbidity. Cell-based strategies employing adipose-derived stromal cells (ASCs), found within the stromal vascular fraction (SVF) of adipose tissue, may offer an alternative strategy for soft tissue reconstruction. In this study, we investigated the potential of a bone morphogenetic protein receptor type 1A (BMPR1A)(+) subpopulation of ASCs to enhance de novo adipogenesis. Human lipoaspirate was enzymatically digested to isolate SVF and magnetic-activated cell separation was utilized to obtain BMPR1A(+) and BMPR1A(-) cells. These cells, along with unenriched cells, were expanded in culture and evaluated for adipogenic gene expression and in vitro adipocyte formation. Cells from each group were also labeled with a green fluorescent protein (GFP) lentivirus and transplanted into the inguinal fat pads, an adipogenic niche, of immunocompromised mice to determine their potential for de novo adipogenesis. Confocal microscopy along with staining of lipid droplets and vasculature was performed to evaluate the formation of mature adipocytes by transplanted cells. In comparison to BMPR1A(-) and unenriched ASCs, BMPR1A(+) cells demonstrated significantly enhanced adipogenesis when cultured in an adipogenic differentiation medium, as evidenced by increased staining with Oil Red O and increased expression of peroxisome proliferator-activating receptor gamma (PPAR-γ) and fatty acid-binding protein 4 (FABP4). BMPR1A(+) cells also formed significantly more adipocytes in vivo, as demonstrated by quantification of GFP+ adipocytes. Minimal formation of mature adipocytes was appreciated by BMPR1A(-) cells. BMPR1A(+) ASCs show an enhanced ability for adipogenesis in vitro, as shown by gene expression and histological staining. Furthermore, within an adipogenic niche, BMPR1A(+) cells possessed an increased capacity

  20. Adipose-derived stem cells for treatment of chronic ulcers

    DEFF Research Database (Denmark)

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

    2018-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  2. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

    Science.gov (United States)

    Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2013-07-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

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

    Directory of Open Access Journals (Sweden)

    Cavirani Sandro

    2010-09-01

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

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

    Science.gov (United States)

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

    2012-09-15

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

  5. Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging

    Directory of Open Access Journals (Sweden)

    Ling-Ran Kong

    2018-04-01

    Full Text Available Functional perivascular adipose tissue (PVAT is necessary to maintain vascular physiology through both mechanical support and endocrine or paracrine ways. PVAT shows a brown adipose tissue (BAT-like feature and the browning level of PVAT is dependent on the anatomic location and species. However, it is not clear whether PVAT browning is involved in the vascular tone regulation in spontaneously hypertensive rats (SHRs. In the present study, we aimed to illustrate the effect of aging on PVAT browning and subsequent vasomotor reaction in SHRs. Herein we utilized histological staining and western blot to detect the characteristics of thoracic PVAT (tPVAT in 8-week-old and 16-week-old SHR and Wistar-Kyoto (WKY rats. We also detected vascular reactivity analysis to determine the effect of tPVAT on vasomotor reaction during aging. The results showed that tPVAT had a similar phenotype to BAT, including smaller adipocyte size and positive uncoupling protein-1 (UCP1 staining. Interestingly, the tPVAT of 8-week-old SHR showed increased BAT phenotypic marker expression compared to WKY, whereas the browning level of tPVAT had a more dramatic decrease from 8 to 16 weeks of age in SHR than age-matched WKY rats. The vasodilation effect of tPVAT on aortas had no significant difference in 8-week-old WKY and SHR, whereas this effect is obviously decreased in 16-week-old SHR compared to WKY. In contrast, tPVAT showed a similar vasoconstriction effect in 8- or 16-week-old WKY and SHR rats. Moreover, we identified an important vasodilator adenosine, which regulates adipocyte browning and may be a potential PVAT-derived relaxing factor. Adenosine is dramatically decreased from 8 to 16 weeks of age in the tPVAT of SHR. In summary, aging is associated with a decrease of tPVAT browning and adenosine production in SHR rats. These may result in attenuated vasodilation effect of the tPVAT in SHR during aging.

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

    Science.gov (United States)

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

    2012-01-01

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

  7. Senescence and quiescence in adipose-derived stromal cells

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Hyeon Joo Kim

    2012-12-01

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

  10. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    International Nuclear Information System (INIS)

    Beane, Olivia S.; Fonseca, Vera C.; Darling, Eric M.

    2014-01-01

    In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

  11. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    Energy Technology Data Exchange (ETDEWEB)

    Beane, Olivia S. [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Fonseca, Vera C. [Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Darling, Eric M., E-mail: Eric_Darling@brown.edu [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Department of Orthopaedics, Brown University, Providence, RI (United States); School of Engineering, Brown University, Providence, RI (United States)

    2014-10-01

    In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

  12. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Science.gov (United States)

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  13. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Chu-Lin Chou

    Full Text Available Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group. Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L. These results suggest a protective role of calcitriol treatment on endothelial

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  15. Arthroscopic Harvest of Adipose-Derived Mesenchymal Stem Cells From the Infrapatellar Fat Pad.

    Science.gov (United States)

    Dragoo, Jason L; Chang, Wenteh

    2017-11-01

    The successful isolation of adipose-derived mesenchymal stem cells (ADSCs) from the arthroscopically harvested infrapatellar fat pad (IFP) would provide orthopaedic surgeons with an autologous solution for regenerative procedures. To demonstrate the quantity and viability of the mesenchymal stem cell population arthroscopically harvested from the IFP as well as the surrounding synovium. Descriptive laboratory study. The posterior border of the IFP, including the surrounding synovial tissue, was harvested arthroscopically from patients undergoing anterior cruciate ligament reconstruction. Tissue was then collected in an AquaVage adipose canister, followed by fat fractionization using syringe emulsification and concentration with an AdiPrep device. In the laboratory, the layers of tissue were separated and then digested with 0.3% type I collagenase. The pelleted stromal vascular fraction (SVF) cells were then immediately analyzed for viability, mesenchymal cell surface markers by fluorescence-activated cell sorting, and clonogenic capacity. After culture expansion, the metabolic activity of the ADSCs was assessed by an AlamarBlue assay, and the multilineage differentiation capability was tested. The transition of surface antigens from the SVF toward expanded ADSCs at passage 2 was further evaluated. SVF cells were successfully harvested with a mean yield of 4.86 ± 2.64 × 10 5 cells/g of tissue and a mean viability of 69.03% ± 10.75%, with ages ranging from 17 to 52 years (mean, 35.14 ± 13.70 years; n = 7). The cultured ADSCs composed a mean 5.85% ± 5.89% of SVF cells with a mean yield of 0.33 ± 0.42 × 10 5 cells/g of tissue. The nonhematopoietic cells (CD45 - ) displayed the following surface antigens as a percentage of the viable population: CD44 + (52.21% ± 4.50%), CD73 + CD90 + CD105 + (19.20% ± 17.04%), and CD44 + CD73 + CD90 + CD105 + (15.32% ± 15.23%). There was also a significant increase in the expression of ADSC markers CD73 (96.97% ± 1.72%; P

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adila A Hamid

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  1. THE NEW SOLUTION OF TIME FRACTIONAL WAVE EQUATION WITH CONFORMABLE FRACTIONAL DERIVATIVE DEFINITION

    OpenAIRE

    Çenesiz, Yücel; Kurt, Ali

    2015-01-01

    – In this paper, we used new fractional derivative definition, the conformable fractional derivative, for solving two and three dimensional time fractional wave equation. This definition is simple and very effective in the solution procedures of the fractional differential equations that have complicated solutions with classical fractional derivative definitions like Caputo, Riemann-Liouville and etc. The results show that conformable fractional derivative definition is usable and convenient ...

  2. Generalized Fractional Derivative Anisotropic Viscoelastic Characterization

    Directory of Open Access Journals (Sweden)

    Harry H. Hilton

    2012-01-01

    Full Text Available Isotropic linear and nonlinear fractional derivative constitutive relations are formulated and examined in terms of many parameter generalized Kelvin models and are analytically extended to cover general anisotropic homogeneous or non-homogeneous as well as functionally graded viscoelastic material behavior. Equivalent integral constitutive relations, which are computationally more powerful, are derived from fractional differential ones and the associated anisotropic temperature-moisture-degree-of-cure shift functions and reduced times are established. Approximate Fourier transform inversions for fractional derivative relations are formulated and their accuracy is evaluated. The efficacy of integer and fractional derivative constitutive relations is compared and the preferential use of either characterization in analyzing isotropic and anisotropic real materials must be examined on a case-by-case basis. Approximate protocols for curve fitting analytical fractional derivative results to experimental data are formulated and evaluated.

  3. Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

    Science.gov (United States)

    Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

    2013-02-01

    Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

  4. Oxidative and inflammatory signals in obesity-associated vascular abnormalities.

    Science.gov (United States)

    Reho, John J; Rahmouni, Kamal

    2017-07-15

    Obesity is associated with increased cardiovascular morbidity and mortality in part due to vascular abnormalities such as endothelial dysfunction and arterial stiffening. The hypertension and other health complications that arise from these vascular defects increase the risk of heart diseases and stroke. Prooxidant and proinflammatory signaling pathways as well as adipocyte-derived factors have emerged as critical mediators of obesity-associated vascular abnormalities. Designing treatments aimed specifically at improving the vascular dysfunction caused by obesity may provide an effective therapeutic approach to prevent the cardiovascular sequelae associated with excessive adiposity. In this review, we discuss the recent evidence supporting the role of oxidative stress and cytokines and inflammatory signals within the vasculature as well as the impact of the surrounding perivascular adipose tissue (PVAT) on the regulation of vascular function and arterial stiffening in obesity. In particular, we focus on the highly plastic nature of the vasculature in response to altered oxidant and inflammatory signaling and highlight how weight management can be an effective therapeutic approach to reduce the oxidative stress and inflammatory signaling and improve vascular function. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

    Science.gov (United States)

    LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

    2016-02-01

    The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

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

    Directory of Open Access Journals (Sweden)

    Davy PMC

    2015-10-01

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

  7. Transdifferentiation of mouse adipose-derived stromal cells into acinar cells of the submandibular gland using a co-culture system

    International Nuclear Information System (INIS)

    Lee, Jingu; Park, Sangkyu; Roh, Sangho

    2015-01-01

    A loss of salivary gland function often occurs after radiation therapy in head and neck tumors, though secretion of saliva by the salivary glands is essential for the health and maintenance of the oral environment. Transplantation of salivary acinar cells (ACs), in part, may overcome the side effects of therapy. Here we directly differentiated mouse adipose-derived stromal cells (ADSCs) into ACs using a co-culture system. Multipotent ADSCs can be easily collected from stromal vascular fractions of adipose tissues. The isolated ADSCs showed positive expression of markers such as integrin beta-1 (CD29), cell surface glycoprotein (CD44), endoglin (CD105), and Nanog. The cells were able to differentiate into adipocytes, osteoblasts, and neural-like cells after 14 days in culture. ADSCs at passage 2 were co-cultured with mouse ACs in AC culture medium using the double-chamber (co-culture system) to avoid mixing the cell types. The ADSCs in this co-culture system expressed markers of ACs, such as α-amylases and aquaporin5, in both mRNA and protein. ADSCs cultured in AC-conditioned medium also expressed AC markers. Cellular proliferation and senescence analyses demonstrated that cells in the co-culture group showed lower senescence and a higher proliferation rate than the AC-conditioned medium group at Days 14 and 21. The results above imply direct conversion of ADSCs into ACs under the co-culture system; therefore, ADSCs may be a stem cell source for the therapy for salivary gland damage. - Highlights: • ADSCs could transdifferentiate into acinar cells (ACs) using ACs co-culture (CCA). • Transdifferentiated ADSCs expressed ACs markers such as α-amylase and aquaporin5. • High proliferation and low senescence were presented in CCA at Day 14. • Transdifferentiation of ADSCs into ACs using CCA may be an appropriate method for cell-based therapy

  8. Transdifferentiation of mouse adipose-derived stromal cells into acinar cells of the submandibular gland using a co-culture system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jingu; Park, Sangkyu; Roh, Sangho, E-mail: sangho@snu.ac.kr

    2015-05-15

    A loss of salivary gland function often occurs after radiation therapy in head and neck tumors, though secretion of saliva by the salivary glands is essential for the health and maintenance of the oral environment. Transplantation of salivary acinar cells (ACs), in part, may overcome the side effects of therapy. Here we directly differentiated mouse adipose-derived stromal cells (ADSCs) into ACs using a co-culture system. Multipotent ADSCs can be easily collected from stromal vascular fractions of adipose tissues. The isolated ADSCs showed positive expression of markers such as integrin beta-1 (CD29), cell surface glycoprotein (CD44), endoglin (CD105), and Nanog. The cells were able to differentiate into adipocytes, osteoblasts, and neural-like cells after 14 days in culture. ADSCs at passage 2 were co-cultured with mouse ACs in AC culture medium using the double-chamber (co-culture system) to avoid mixing the cell types. The ADSCs in this co-culture system expressed markers of ACs, such as α-amylases and aquaporin5, in both mRNA and protein. ADSCs cultured in AC-conditioned medium also expressed AC markers. Cellular proliferation and senescence analyses demonstrated that cells in the co-culture group showed lower senescence and a higher proliferation rate than the AC-conditioned medium group at Days 14 and 21. The results above imply direct conversion of ADSCs into ACs under the co-culture system; therefore, ADSCs may be a stem cell source for the therapy for salivary gland damage. - Highlights: • ADSCs could transdifferentiate into acinar cells (ACs) using ACs co-culture (CCA). • Transdifferentiated ADSCs expressed ACs markers such as α-amylase and aquaporin5. • High proliferation and low senescence were presented in CCA at Day 14. • Transdifferentiation of ADSCs into ACs using CCA may be an appropriate method for cell-based therapy.

  9. 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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sadanori Akita

    2010-01-01

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

  12. Successful Isolation of Viable Adipose-Derived Stem Cells from Human Adipose Tissue Subject to Long-Term Cryopreservation: Positive Implications for Adult Stem Cell-Based Therapeutics in Patients of Advanced Age

    Directory of Open Access Journals (Sweden)

    Sean M. Devitt

    2015-01-01

    Full Text Available We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2–1159 days from patients of varying ages (26–62 years. Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved 2 years, irrespective of patient age. However, this difference did not persist with continued growth and there were no significant differences in cell viability or growth at subsequent time points with respect to cryopreservation duration or patient age. Mesenchymal stem cell markers were maintained in all cohorts tested throughout the duration of the study. Consequently, longer cryopreservation negatively impacts initial live adipose-derived stem cell isolation; however, this effect is neutralized with continued cell growth. Patient age does not significantly impact stem cell isolation, viability, or growth. Cryopreservation of adipose tissue is an effective long-term banking method for isolation of adipose-derived stem cells in patients of varying ages.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Ann Katharin Reckhenrich

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

  15. Fractional variational calculus in terms of Riesz fractional derivatives

    International Nuclear Information System (INIS)

    Agrawal, O P

    2007-01-01

    This paper presents extensions of traditional calculus of variations for systems containing Riesz fractional derivatives (RFDs). Specifically, we present generalized Euler-Lagrange equations and the transversality conditions for fractional variational problems (FVPs) defined in terms of RFDs. We consider two problems, a simple FVP and an FVP of Lagrange. Results of the first problem are extended to problems containing multiple fractional derivatives, functions and parameters, and to unspecified boundary conditions. For the second problem, we present Lagrange-type multiplier rules. For both problems, we develop the Euler-Lagrange-type necessary conditions which must be satisfied for the given functional to be extremum. Problems are considered to demonstrate applications of the formulations. Explicitly, we introduce fractional momenta, fractional Hamiltonian, fractional Hamilton equations of motion, fractional field theory and fractional optimal control. The formulations presented and the resulting equations are similar to the formulations for FVPs given in Agrawal (2002 J. Math. Anal. Appl. 272 368, 2006 J. Phys. A: Math. Gen. 39 10375) and to those that appear in the field of classical calculus of variations. These formulations are simple and can be extended to other problems in the field of fractional calculus of variations

  16. Adipose Tissue Biology: An Update Review

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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

  19. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

    Science.gov (United States)

    Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

    2013-10-01

    Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

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

    Science.gov (United States)

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

    2009-04-01

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

  1. Perivascular adipose tissue: more than just structural support.

    Science.gov (United States)

    Szasz, Theodora; Webb, R Clinton

    2012-01-01

    PVAT (perivascular adipose tissue) has recently been recognized as a novel factor in vascular biology, with implications in the pathophysiology of cardiovascular disease. Composed mainly of adipocytes, PVAT releases a wide range of biologically active molecules that modulate vascular smooth muscle cell contraction, proliferation and migration. PVAT exerts an anti-contractile effect in various vascular beds which seems to be mediated by an as yet elusive PVRF [PVAT-derived relaxing factor(s)]. Considerable progress has been made on deciphering the nature and mechanisms of action of PVRF, and the PVRFs proposed until now are reviewed here. However, complex pathways seem to regulate PVAT function and more than one mechanism is probably responsible for PVAT actions in vascular biology. The present review describes our current knowledge on the structure and function of PVAT, with a focus on its role in modulating vascular tone. Potential involvements of PVAT dysfunction in obesity, hypertension and atherosclerosis will be highlighted.

  2. The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair.

    Directory of Open Access Journals (Sweden)

    Dezhong Yang

    Full Text Available BACKGROUND: Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC can improve cardiac function in animal models of myocardial infarction (MI. However, the mechanisms underlying the beneficial effect are not fully understood. In this study, we characterized the paracrine effect of transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair. METHODOLOGY/PRINCIPAL FINDINGS: MI was experimentally induced in mice by ligation of the left anterior descending coronary artery. Either human ADSC, conditioned medium (CM collected from the same amount of ADSC or control medium was injected into the peri-infarct region immediately after MI. Compared with the control group, both ADSC and ADSC-CM significantly reduced myocardial infarct size and improved cardiac function. The therapeutic efficacy of ADSC was moderately superior to ADSC-CM. ADSC-CM significantly reduced cardiomyocyte apoptosis in the infarct border zone, to a similar degree with ADSC treatment. ADSC enhanced angiogenesis in the infarct border zone, but to a stronger degree than that seen in the ADSC-CM treatment. ADSC was able to differentiate to endothelial cell and smooth muscle cell in post-MI heart; these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found. CONCLUSIONS: ADSC-CM is sufficient to improve cardiac function of infarcted hearts. The therapeutic function of ADSC transplantation is mainly induced by paracrine-mediated cardioprotection and angiogenesis, while ADSC differentiation contributes a minor benefit by being involved in angiogenesis. Highlights 1 ADSC-CM is sufficient to exert a therapeutic potential. 2. ADSC was able to differentiate to vascular cells but not cardiomyocyte. 3. ADSC derived vascular cells amount to about 9% of the enhanced angiogenesis. 4. Paracrine effect is the major

  3. Adipose-Derived Cell Construct Stabilizes Heart Function and Increases Microvascular Perfusion in an Established Infarct

    Science.gov (United States)

    Nguyen, Quang T.; Touroo, Jeremy S.; Aird, Allison L.; Chang, Raymond C.; Ng, Chin K.; Hoying, James B.; Williams, Stuart K.

    2013-01-01

    We have previously shown that myocardial infarction (MI) immediately treated with an epicardial construct containing stromal vascular fraction (SVF) from adipose tissue preserved microvascular function and left ventricle contractile mechanisms. In order to evaluate a more clinically relevant condition, we investigated the cardiac recovery potential of an SVF construct implanted onto an established infarct. SVF cells were isolated from rat adipose tissue, plated on Vicryl, and cultured for 14 days. Fischer-344 rats were separated into MI groups: (a) 6-week MI (MI), (b) 6-week MI treated with an SVF construct at 2 weeks (MI SVF), (c) 6-week MI with Vicryl construct at 2 weeks (MI Vicryl), and (d) MI 2wk (time point of intervention). Emax, an indicator of systolic performance and contractile function, was lower in the MI and MI Vicryl versus MI SVF. Positron emission tomography imaging (18F-fluorodeoxyglucose) revealed a decreased percentage of relative infarct volume in the MI SVF versus MI and MI Vicryl. Total vessel count and percentage of perfusion assessed via immunohistochemistry were both increased in the infarct region of MI SVF versus MI and MI Vicryl. Overall cardiac function, percentage of relative infarct, and percentage of perfusion were similar between MI SVF and MI 2wk; however, total vessel count increased after SVF treatment. These data suggest that SVF treatment of an established infarct stabilizes the heart at the time point of intervention by preventing a worsening of cardiac performance and infarcted volume, and is associated with increased microvessel perfusion in the area of established infarct. PMID:24106337

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

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

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

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-10

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  8. 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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  10. Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes

    DEFF Research Database (Denmark)

    Elabd, Christian; Chiellini, Chiara; Carmona, Mamen

    2009-01-01

    adipose-derived stem (hMADS) cells exhibit a normal karyotype and high self-renewal ability; they are known to differentiate into cells that exhibit the key properties of human white adipocytes, that is, uncoupling protein two expression, insulin-stimulated glucose uptake, lipolysis in response to beta......In contrast to the earlier contention, adult humans have been shown recently to possess active brown adipose tissue with a potential of being of metabolic significance. Up to now, brown fat precursor cells have not been available for human studies. We have shown previously that human multipotent......-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARgamma but not to a PPARbeta/delta or a PPARalpha agonist, hMADS cell-derived white adipocytes are able to switch to a brown phenotype by expressing both uncoupling protein one...

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

    Science.gov (United States)

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

    2018-04-01

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

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. State-Space Modelling of Loudspeakers using Fractional Derivatives

    DEFF Research Database (Denmark)

    King, Alexander Weider; Agerkvist, Finn T.

    2015-01-01

    This work investigates the use of fractional order derivatives in modeling moving-coil loudspeakers. A fractional order state-space solution is developed, leading the way towards incorporating nonlinearities into a fractional order system. The method is used to calculate the response of a fractio......This work investigates the use of fractional order derivatives in modeling moving-coil loudspeakers. A fractional order state-space solution is developed, leading the way towards incorporating nonlinearities into a fractional order system. The method is used to calculate the response...... of a fractional harmonic oscillator, representing the mechanical part of a loudspeaker, showing the effect of the fractional derivative and its relationship to viscoelasticity. Finally, a loudspeaker model with a fractional order viscoelastic suspension and fractional order voice coil is fit to measurement data...

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

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    Angelo A. Leto Barone

    2013-01-01

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

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

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    Herold, C.

    2012-09-01

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

  17. Adipose-derived stromal vascular fraction cells and platelet-rich plasma: basic and clinical evaluation for cell-based therapies in patients with scars on the face.

    Science.gov (United States)

    Gentile, Pietro; De Angelis, Barbara; Pasin, Methap; Cervelli, Giulio; Curcio, Cristiano B; Floris, Micol; Di Pasquali, Camilla; Bocchini, Ilaria; Balzani, Alberto; Nicoli, Fabio; Insalaco, Chiara; Tati, Eleonora; Lucarini, Lucilla; Palla, Ludovico; Pascali, Michele; De Logu, Pamela; Di Segni, Chiara; Bottini, Davide J; Cervelli, Valerio

    2014-01-01

    Actually, autologous fat grafts have many clinical applications in breast surgery, facial rejuvenation, buttock augmentation, and Romberg syndrome as well as a treatment of liposuction sequelae. The aim of this article was to describe the preparation and isolation procedures for stromal vascular fraction (SVF), the preparation of platelet-rich plasma (PRP), and the clinical application in the treatment of the scar on the face. Ten patients with burns sequelae (n = 6) and post-traumatic scars (n = 4) were treated with SVF-enhanced autologous fat grafts obtained by the Celution System. Another 10 patients with burns sequelae (n = 5) and post-traumatic scars (n = 5) were treated with fat grafting based on the Coleman technique mixed with 0.5 mL of PRP.To assess the effects of their treatment, the authors compared their results with those of a control group consisting of 10 patients treated with centrifuged fat. In the patients treated with SVF-enhanced autologous fat grafts, we observed a 63% maintenance of contour restoring after 1 year compared with only 39% of the control group (n = 10) treated with centrifuged fat graft (P < 0.0001). In the patients treated with fat grafting and PRP, we observed a 69% maintenance of contour restoring after 1 year compared with that of the control group (n = 10). Autologous fat grafting is a good method for the correction of scars on the face instead of the traditional scar surgical excision.

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

    Directory of Open Access Journals (Sweden)

    Fang-tian Xu

    2014-11-01

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

  19. Lipoinjerto laminar: un tratamiento prometedor con factores vasculares estromales para las vulvo-vaginitis crónicas Lipoenxertia laminar: um tratamento promissor com factores vasculares estromais para as vulvo-vaginetes crônicas Lamellar fatgrafting: a promissing treatment with stromal vascular fraction in recurrent vulvo-vaginitis

    Directory of Open Access Journals (Sweden)

    Ithamar N. Stocchero

    2009-09-01

    herpes infection, with its permanent pain, the sexual life of the couple will be a point of discordance that may lead to an unsustainable intimacy. The authors relate a successful case of a new treatment that consists in a submucosal lamellar fatgrafting, with preservation of the stromal vascular fraction (SFV rich in Adipose Derived Stromal/Stem Cells (ADSCs and able to induce a neoangiogenesis, that will promote the normal immunological defense of the mucosa of the vagina, providing against the use of antibiotics and expensive therapies, and, most of all, leading to a normal sexual life. The successful technique used in this case is described in the article.

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

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    Wilfredo Oliva-Olivera

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

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    Farah Fatima

    2017-08-01

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

  3. Culture expansion of adipose derived stromal cells. A closed automated Quantum Cell Expansion System compared with manual flask-based culture

    Directory of Open Access Journals (Sweden)

    Mandana Haack-Sørensen

    2016-11-01

    Full Text Available Abstract Background Adipose derived stromal cells (ASCs are a rich and convenient source of cells for clinical regenerative therapeutic approaches. However, applications of ASCs often require cell expansion to reach the needed dose. In this study, cultivation of ASCs from stromal vascular fraction (SVF over two passages in the automated and functionally closed Quantum Cell Expansion System (Quantum system is compared with traditional manual cultivation. Methods Stromal vascular fraction was isolated from abdominal fat, suspended in α-MEM supplemented with 10% Fetal Bovine Serum and seeded into either T75 flasks or a Quantum system that had been coated with cryoprecipitate. The cultivation of ASCs from SVF was performed in 3 ways: flask to flask; flask to Quantum system; and Quantum system to Quantum system. In all cases, quality controls were conducted for sterility, mycoplasmas, and endotoxins, in addition to the assessment of cell counts, viability, immunophenotype, and differentiation potential. Results The viability of ASCs passage 0 (P0 and P1 was above 96%, regardless of cultivation in flasks or Quantum system. Expression of surface markers and differentiation potential was consistent with ISCT/IFATS standards for the ASC phenotype. Sterility, mycoplasma, and endotoxin tests were consistently negative. An average of 8.0 × 107 SVF cells loaded into a Quantum system yielded 8.96 × 107 ASCs P0, while 4.5 × 106 SVF cells seeded per T75 flask yielded an average of 2.37 × 106 ASCs—less than the number of SVF cells seeded. ASCs P1 expanded in the Quantum system demonstrated a population doubling (PD around 2.2 regardless of whether P0 was previously cultured in flasks or Quantum, while ASCs P1 in flasks only reached a PD of 1.0. Conclusion: Manufacturing of ASCs in a Quantum system enhances ASC expansion rate and yield significantly relative to manual processing in T-flasks, while maintaining the purity and quality essential to

  4. Culture expansion of adipose derived stromal cells. A closed automated Quantum Cell Expansion System compared with manual flask-based culture.

    Science.gov (United States)

    Haack-Sørensen, Mandana; Follin, Bjarke; Juhl, Morten; Brorsen, Sonja K; Søndergaard, Rebekka H; Kastrup, Jens; Ekblond, Annette

    2016-11-16

    Adipose derived stromal cells (ASCs) are a rich and convenient source of cells for clinical regenerative therapeutic approaches. However, applications of ASCs often require cell expansion to reach the needed dose. In this study, cultivation of ASCs from stromal vascular fraction (SVF) over two passages in the automated and functionally closed Quantum Cell Expansion System (Quantum system) is compared with traditional manual cultivation. Stromal vascular fraction was isolated from abdominal fat, suspended in α-MEM supplemented with 10% Fetal Bovine Serum and seeded into either T75 flasks or a Quantum system that had been coated with cryoprecipitate. The cultivation of ASCs from SVF was performed in 3 ways: flask to flask; flask to Quantum system; and Quantum system to Quantum system. In all cases, quality controls were conducted for sterility, mycoplasmas, and endotoxins, in addition to the assessment of cell counts, viability, immunophenotype, and differentiation potential. The viability of ASCs passage 0 (P0) and P1 was above 96%, regardless of cultivation in flasks or Quantum system. Expression of surface markers and differentiation potential was consistent with ISCT/IFATS standards for the ASC phenotype. Sterility, mycoplasma, and endotoxin tests were consistently negative. An average of 8.0 × 10 7 SVF cells loaded into a Quantum system yielded 8.96 × 10 7 ASCs P0, while 4.5 × 10 6 SVF cells seeded per T75 flask yielded an average of 2.37 × 10 6 ASCs-less than the number of SVF cells seeded. ASCs P1 expanded in the Quantum system demonstrated a population doubling (PD) around 2.2 regardless of whether P0 was previously cultured in flasks or Quantum, while ASCs P1 in flasks only reached a PD of 1.0. Manufacturing of ASCs in a Quantum system enhances ASC expansion rate and yield significantly relative to manual processing in T-flasks, while maintaining the purity and quality essential to safe and robust cell production. Notably, the use of the Quantum

  5. Adipose-derived stem cells - Methods and protocols

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2011-09-01

    Full Text Available This book is pleasing the reader already by the Authors’ preface. It is one in a million case to find a figure or a graph in the foreword presentation of a book. Here, Professors Gimble and Bunnell decided to give a warning to the reader about the increasing relevance that the topics covered by the book is playing in the life sciences researches: they simply decided to show the ISI Web of knowledge annual publications and citations for adipose stem cells. Clear enough, the statistics is impressive: few papers in 2000, nearly 600 in 2009 and 2010. The same pattern is present in the citations per year, quite a few in 2000 – 2001 and something like 12,000 in 2010 ! I think that these numbers justify the idea to have a volume devoted to cover all of the topics related to these intriguing stem cell type, likely originating from a perivascular histological niche within highly vascularized fat tissue. The book is divided in four parts.......

  6. Fractional Hamiltonian analysis of higher order derivatives systems

    International Nuclear Information System (INIS)

    Baleanu, Dumitru; Muslih, Sami I.; Tas, Kenan

    2006-01-01

    The fractional Hamiltonian analysis of 1+1 dimensional field theory is investigated and the fractional Ostrogradski's formulation is obtained. The fractional path integral of both simple harmonic oscillator with an acceleration-squares part and a damped oscillator are analyzed. The classical results are obtained when fractional derivatives are replaced with the integer order derivatives

  7. Migraine and tension-type headache treated with stromal vascular fraction: a case series.

    Science.gov (United States)

    Bright, Ralph; Bright, Matthew; Bright, Pelin; Hayne, Shannon; Thomas, Wayne D

    2014-06-30

    Chronic migraines and tension-type headaches are debilitating diseases affecting 1.4 to 2.2% of the population with both quality of life and economic implications. To date, the pain associated with migraine and tension-type headaches has been controlled with a range of medications, with varying levels of success. In addition, the side-effect profile of these medications, as well as their potential for addiction, has been a cause for concern for both patients and physicians. Four women with long histories of migraine or frequent tension-type headache that meet the International Classification of Headache Disorders criteria for Chronic Migraine or Tension-type Headaches were given a systemic treatment(s) of autologous stromal vascular fraction or autologous 'StroMed' isolated from lipoaspirate. StroMed is stromal vascular fraction cells prepared by ultrasonic cavitation. Two of the four patients, both of whom are Arab women aged 40 and 36 years, ceased having migraines after 1 month, for a period of 12 to 18 months. The third patient, a Slavic woman aged 43 years, had a significant decrease in the frequency and severity of migraines with only seven migraines over 18 months. The fourth patient, an Asian woman aged 44 years, obtained a temporary decrease for a period of a month and was retreated 18 months later and has been free of migraines to date for 1 month. Pain medication was typically reduced from prescribed opioid analgesia to non-steroidal anti-inflammatory drugs and paracetamol. This case series is the first to provide evidence of the efficacy of autologous StroMed and stromal vascular fraction in the treatment of migraine and tension-type headache. The treatment of this disease by stromal vascular fraction adds a new dimension to its clinical applicability and suggests a relatively simple treatment that may help address the symptoms of the disease. Given what is known about the components of the stromal vascular fraction and how they act, the information

  8. Cryoablation in fibro-adipose vascular anomaly (FAVA): a minimally invasive treatment option

    International Nuclear Information System (INIS)

    Shaikh, Raja; Alomari, Ahmad I.; Kerr, Cindy L.; Miller, Patricia; Spencer, Samantha A.

    2016-01-01

    Fibro-adipose vascular anomaly (FAVA) is a complex vascular malformation that typically presents with persistent pain, discomfort, contracture and other disabling symptoms. There are no minimally invasive treatment options to effectively control these symptoms. Image-guided percutaneous cryoablation, which has been used to control pain in people with cancer, could be used for similar indications in FAVA. To assess the role of image-guided percutaneous cryoablation for control of symptoms in FAVA lesions. We conducted a retrospective cohort study of 20 children and young adults with FAVA who underwent percutaneous cryoablation at 26 sites, from September 2013 to August 2015. The outcome was based on the brief pain inventory scoring (BPI), concurrent symptoms, clinical response and patient satisfaction. After cryoablation there was significant improvement in pain, which dropped by 3 points (pain now) to 3.7 points (pain in the last 24 h). Most patients indicated that pain interfered less in their everyday social life. Concurrent symptoms like swelling, physical limitations and skin hyperesthesia also improved. Clinical response was greatest at 2-5 months follow-up after cryoablation, with acceptable patient satisfaction thereafter. Technical response was 100%. There were no major complications. Image-guided percutaneous cryoablation is a safe and effective option for treatment of symptomatic FAVA lesions. (orig.)

  9. Non-Noether symmetries of Hamiltonian systems with conformable fractional derivatives

    International Nuclear Information System (INIS)

    Wang Lin-Li; Fu Jing-Li

    2016-01-01

    In this paper, we present the fractional Hamilton’s canonical equations and the fractional non-Noether symmetry of Hamilton systems by the conformable fractional derivative. Firstly, the exchanging relationship between isochronous variation and fractional derivatives, and the fractional Hamilton principle of the system under this fractional derivative are proposed. Secondly, the fractional Hamilton’s canonical equations of Hamilton systems based on the Hamilton principle are established. Thirdly, the fractional non-Noether symmetries, non-Noether theorem and non-Noether conserved quantities for the Hamilton systems with the conformable fractional derivatives are obtained. Finally, an example is given to illustrate the results. (paper)

  10. Control and Synchronization of the Fractional-Order Lorenz Chaotic System via Fractional-Order Derivative

    Directory of Open Access Journals (Sweden)

    Ping Zhou

    2012-01-01

    Full Text Available The unstable equilibrium points of the fractional-order Lorenz chaotic system can be controlled via fractional-order derivative, and chaos synchronization for the fractional-order Lorenz chaotic system can be achieved via fractional-order derivative. The control and synchronization technique, based on stability theory of fractional-order systems, is simple and theoretically rigorous. The numerical simulations demonstrate the validity and feasibility of the proposed method.

  11. Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function.

    Science.gov (United States)

    Bagno, Luiza L; Carvalho, Deivid; Mesquita, Fernanda; Louzada, Ruy A; Andrade, Bruno; Kasai-Brunswick, Taís H; Lago, Vivian M; Suhet, Grazielle; Cipitelli, Debora; Werneck-de-Castro, João Pedro; Campos-de-Carvalho, Antonio C

    2016-01-01

    The mechanism by which stem cell-based therapy improves heart function is still unknown, but paracrine mechanisms seem to be involved. Adipose-derived stem cells (ADSCs) secrete several factors, including insulin-like growth factor-1 (IGF-1), which may contribute to myocardial regeneration. Our aim was to investigate whether the overexpression of IGF-1 in ADSCs (IGF-1-ADSCs) improves treatment of chronically infarcted rat hearts. ADSCs were transduced with a lentiviral vector to induce IGF-1 overexpression. IGF-1-ADSCs transcribe100- to 200-fold more IGF-1 mRNA levels compared to nontransduced ADSCs. IGF-1 transduction did not alter ADSC immunophenotypic characteristics even under hypoxic conditions. However, IGF-1-ADSCs proliferate at higher rates and release greater amounts of growth factors such as IGF-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) under normoxic and hypoxic conditions. Importantly, IGF-1 secreted by IGF-1-ADSCs is functional given that Akt-1 phosphorylation was remarkably induced in neonatal cardiomyocytes cocultured with IGF-1-ADSCs, and this increase was prevented with phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. Next, we tested IGF-1-ADSCs in a rat myocardial infarction (MI) model. MI was performed by coronary ligation, and 4 weeks after MI, animals received intramyocardial injections of either ADSCs (n = 7), IGF-1-ADSCs (n = 7), or vehicle (n = 7) into the infarcted border zone. Left ventricular function was evaluated by echocardiography before and after 6 weeks of treatment, and left ventricular hemodynamics were assessed 7 weeks after cell injection. Notably, IGF-1-ADSCs improved left ventricular ejection fraction and cardiac contractility index, but did not reduce scar size when compared to the ADSC-treated group. In summary, transplantation of ADSCs transduced with IGF-1 is a superior therapeutic approach to treat MI compared to nontransduced ADSCs, suggesting that gene and cell

  12. Influence of smartphone Wi-Fi signals on adipose-derived stem cells.

    Science.gov (United States)

    Lee, Sang-Soon; Kim, Hyung-Rok; Kim, Min-Sook; Park, Sanghoon; Yoon, Eul-Sik; Park, Seung-Ha; Kim, Deok-Woo

    2014-09-01

    The use of smartphones is expanding rapidly around the world, thus raising the concern of possible harmful effects of radiofrequency generated by smartphones. We hypothesized that Wi-Fi signals from smartphones may have harmful influence on adipose-derived stem cells (ASCs). An in vitro study was performed to assess the influence of Wi-Fi signals from smartphones. The ASCs were incubated under a smartphone connected to a Wi-Fi network, which was uploading files at a speed of 4.8 Mbps for 10 hours a day, for a total of 5 days. We constructed 2 kinds of control cells, one grown in 37°C and the other grown in 39°C. After 5 days of Wi-Fi exposure from the smartphone, the cells underwent cell proliferation assay, apoptosis assay, and flow cytometry analysis. Three growth factors, vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor-β, were measured from ASC-conditioned media. Cell proliferation rate was higher in Wi-Fi-exposed cells and 39°C control cells compared with 37°C control cells. Apoptosis assay, flow cytometry analysis, and growth factor concentrations showed no remarkable differences among the 3 groups. We could not find any harmful effects of Wi-Fi electromagnetic signals from smartphones. The increased proliferation of ASCs under the smartphone, however, might be attributable to the thermal effect.

  13. Evaluation of gold nanotracers to track adipose-derived stem cells in a PEGylated fibrin gel for dermal tissue engineering applications

    Directory of Open Access Journals (Sweden)

    Chung E

    2013-01-01

    Full Text Available Eunna Chung,1 Seung Yun Nam,1,2 Laura M Ricles,1 Stanislav Y Emelianov,1,2 Laura J Suggs11Department of Biomedical Engineering, 2Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, TX, USAAbstract: Evaluating the regenerative capacity of a tissue-engineered device in a noninvasive and synchronous manner is critical to determining the mechanisms for success in clinical applications. In particular, directly tracking implanted cells in a three-dimensional (3D scaffold is desirable in that it enables the monitoring of cellular activity in a specific and localized manner. The authors' group has previously demonstrated that the PEGylation of fibrin results in a 3D scaffold that supports morphologic and phenotypic changes in mesenchymal stem cells that may be advantageous in wound healing applications. Recently, the authors have evaluated adipose-derived stem cells (ASCs as a mesenchymal cell source to regenerate skin and blood vessels due to their potential for proliferation, differentiation, and production of growth factors. However, tracking and monitoring ASCs in a 3D scaffold, such as a PEGylated fibrin gel, have not yet been fully investigated. In the current paper, nanoscale gold spheres (20 nm as cell tracers for ASCs cultured in a PEGylated fibrin gel were evaluated. An advanced dual-imaging modality combining ultrasound and photoacoustic imaging was utilized to monitor rat ASCs over time. The ASCs took up gold nanotracers and could be detected up to day 16 with high sensitivity using photoacoustic imaging. There were no detrimental effects on ASC morphology, network formation, proliferation, and protein expression/secretion (ie, smooth muscle α-actin, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 associated with gold nanotracers. Therefore, utilization of gold nanotracers can be an effective strategy to monitor the regenerative process of a stem cell

  14. Generalized fractional Schroedinger equation with space-time fractional derivatives

    International Nuclear Information System (INIS)

    Wang Shaowei; Xu Mingyu

    2007-01-01

    In this paper the generalized fractional Schroedinger equation with space and time fractional derivatives is constructed. The equation is solved for free particle and for a square potential well by the method of integral transforms, Fourier transform and Laplace transform, and the solution can be expressed in terms of Mittag-Leffler function. The Green function for free particle is also presented in this paper. Finally, we discuss the relationship between the cases of the generalized fractional Schroedinger equation and the ones in standard quantum

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Variational problems with fractional derivatives: Euler-Lagrange equations

    International Nuclear Information System (INIS)

    Atanackovic, T M; Konjik, S; Pilipovic, S

    2008-01-01

    We generalize the fractional variational problem by allowing the possibility that the lower bound in the fractional derivative does not coincide with the lower bound of the integral that is minimized. Also, for the standard case when these two bounds coincide, we derive a new form of Euler-Lagrange equations. We use approximations for fractional derivatives in the Lagrangian and obtain the Euler-Lagrange equations which approximate the initial Euler-Lagrange equations in a weak sense

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

    Science.gov (United States)

    Tanzi, Maria Cristina; Farè, Silvia

    2009-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Peraldi Pascal

    2008-02-01

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

  19. Measuring memory with the order of fractional derivative

    Science.gov (United States)

    Du, Maolin; Wang, Zaihua; Hu, Haiyan

    2013-12-01

    Fractional derivative has a history as long as that of classical calculus, but it is much less popular than it should be. What is the physical meaning of fractional derivative? This is still an open problem. In modeling various memory phenomena, we observe that a memory process usually consists of two stages. One is short with permanent retention, and the other is governed by a simple model of fractional derivative. With the numerical least square method, we show that the fractional model perfectly fits the test data of memory phenomena in different disciplines, not only in mechanics, but also in biology and psychology. Based on this model, we find that a physical meaning of the fractional order is an index of memory.

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

    Science.gov (United States)

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

    2015-05-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  2. Analysis of Drude model using fractional derivatives without singular kernels

    Directory of Open Access Journals (Sweden)

    Jiménez Leonardo Martínez

    2017-11-01

    Full Text Available We report study exploring the fractional Drude model in the time domain, using fractional derivatives without singular kernels, Caputo-Fabrizio (CF, and fractional derivatives with a stretched Mittag-Leffler function. It is shown that the velocity and current density of electrons moving through a metal depend on both the time and the fractional order 0 < γ ≤ 1. Due to non-singular fractional kernels, it is possible to consider complete memory effects in the model, which appear neither in the ordinary model, nor in the fractional Drude model with Caputo fractional derivative. A comparison is also made between these two representations of the fractional derivatives, resulting a considered difference when γ < 0.8.

  3. Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Sowa

    Full Text Available Recent studies have shown that adipose-derived stromal/stem cells (ASCs contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs. This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2 and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta. NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

  4. Male bovine GH transgenic mice have decreased adiposity with an adipose depot-specific increase in immune cell populations.

    Science.gov (United States)

    Benencia, Fabian; Harshman, Stephanie; Duran-Ortiz, Silvana; Lubbers, Ellen R; List, Edward O; Householder, Lara; Al-Naeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie; Kopchick, John J; Berryman, Darlene E

    2015-05-01

    White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner.

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

    Science.gov (United States)

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

    2018-04-01

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

  6. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lauren H. Mangum

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ji-qing Cao

    2016-01-01

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

  10. Role of adipose-derived stem cells in wound healing.

    Science.gov (United States)

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

    2014-01-01

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

  11. Adipose-Derived Stem Cells

    NARCIS (Netherlands)

    Gathier, WA; Türktas, Z; Duckers, HJ

    2015-01-01

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

  12. Large deflection of viscoelastic beams using fractional derivative model

    International Nuclear Information System (INIS)

    Bahranini, Seyed Masoud Sotoodeh; Eghtesad, Mohammad; Ghavanloo, Esmaeal; Farid, Mehrdad

    2013-01-01

    This paper deals with large deflection of viscoelastic beams using a fractional derivative model. For this purpose, a nonlinear finite element formulation of viscoelastic beams in conjunction with the fractional derivative constitutive equations has been developed. The four-parameter fractional derivative model has been used to describe the constitutive equations. The deflected configuration for a uniform beam with different boundary conditions and loads is presented. The effect of the order of fractional derivative on the large deflection of the cantilever viscoelastic beam, is investigated after 10, 100, and 1000 hours. The main contribution of this paper is finite element implementation for nonlinear analysis of viscoelastic fractional model using the storage of both strain and stress histories. The validity of the present analysis is confirmed by comparing the results with those found in the literature.

  13. Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography

    International Nuclear Information System (INIS)

    Ng, Q.-S.; Goh, Vicky; Milner, Jessica; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J.

    2007-01-01

    Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery and center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center

  14. Adipose-derived adult stem cells: available technologies for potential clinical regenerative applications in dentistry.

    Science.gov (United States)

    Catalano, Enrico; Cochis, Andrea; Varoni, Elena; Rimondini, Lia; Carrassi, Antonio; Azzimonti, Barbara

    2013-01-01

    Tissue homeostasis depends closely on the activity and welfare of adult stem cells. These cells represent a promising tool for biomedical research since they can aid in treatment and promote the regeneration of damaged organs in many human disorders. Adult stem cells indefinitely preserve their ability to self-renew and differentiate into various phenotypes; this capacity could be promoted in vitro by particular culture conditions (differentiation media) or spontaneously induced in vivo by exploiting the biochemical and mechanical properties of the tissue in which the stem cells are implanted. Among the different sources of adult stem cells, adipose tissue is an attractive possibility thanks to its ready availability and the standard extraction techniques at our disposal today. This review discusses the isolation, characterization, and differentiation of human adipose-derived adult stem cells, as well as regeneration strategies, therapeutic uses, and adverse effects of their delivery. In particular, since oral disorders (e.g., trauma, erosion, and chronic periodontitis) often cause the loss of dental tissue along with functional, phonetic, and aesthetic impairment, this review focuses on the application of human adipose-derived adult stem cells, alone or in combination with biomaterials, in treating oral diseases.

  15. The efficacy of conditioned media of adipose-derived stem cells combined with ablative carbon dioxide fractional resurfacing for atrophic acne scars and skin rejuvenation.

    Science.gov (United States)

    Zhou, Bing-Rong; Zhang, Ting; Bin Jameel, Afzaal Ahmed; Xu, Yang; Xu, Yan; Guo, Shi-Lei; Wang, Ying; Permatasari, Felicia; Luo, Dan

    2016-06-01

    To evaluate the effects of conditioned medium of adipose-derived stem cells (ADSC-CM) on efficacy and side effects after fractional carbon dioxide laser resurfacing (FxCR) when treating subjects with facial atrophic acne scars or with skin rejuvenation needs. Twenty-two subjects were enrolled in the study and divided into two groups. Nine subjects were included in skin rejuvenation group and thirteen subjects were included in acne scar group, and all subjects underwent three sessions of FxCR. ADSC-CM was applied on FxCR site of one randomly selected face side. Evaluations were done at baseline, 1 week after first treatment, and 1 month after each treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, transepidermal water loss (TEWL), and the erythema and melanin index. Biopsies taken from one subject in skin rejuvenation group were analyzed using hematoxylin and eosin, Masson's Trichrome, and Gomori's aldehyde fuchsin staining. ADSC-CM combined with FxCR increased subject satisfaction, elasticity, skin hydration, and skin elasticity and decreased TEWL, roughness, and the melanin index in both acne scars and skin rejuvenation groups. Histologic analysis showed that ADSC-CM increased dermal collagen density, elastin density, and arranged them in order. ADSC-CM with FxCR is a good combination therapy for treating atrophic acne scars and skin rejuvenation. JSPH2012-082 - Registered 14 Feb 2012.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Adipocytes Impair Efficacy of Antiretroviral Therapy

    Science.gov (United States)

    Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

    2018-01-01

    Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

  18. Weight-dependent changes of immune system in adipose tissue: Importance of leptin

    International Nuclear Information System (INIS)

    Caspar-Bauguil, S.; Cousin, B.; Andre, M.; Nibbelink, M.; Galinier, A.; Periquet, B.; Casteilla, L.; Penicaud, L.

    2006-01-01

    Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage of NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral γδ T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the αβ T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations

  19. 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

  20. On some new properties of fractional derivatives with Mittag-Leffler kernel

    Science.gov (United States)

    Baleanu, Dumitru; Fernandez, Arran

    2018-06-01

    We establish a new formula for the fractional derivative with Mittag-Leffler kernel, in the form of a series of Riemann-Liouville fractional integrals, which brings out more clearly the non-locality of fractional derivatives and is easier to handle for certain computational purposes. We also prove existence and uniqueness results for certain families of linear and nonlinear fractional ODEs defined using this fractional derivative. We consider the possibility of a semigroup property for these derivatives, and establish extensions of the product rule and chain rule, with an application to fractional mechanics.

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

    Directory of Open Access Journals (Sweden)

    Yu. В. Basok

    2018-01-01

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

  2. 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

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

    Science.gov (United States)

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

    2008-11-01

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

  4. Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients.

    Science.gov (United States)

    Virzì, Francesco; Bianca, Paola; Giammona, Alessandro; Apuzzo, Tiziana; Di Franco, Simone; Mangiapane, Laura Rosa; Colorito, Maria Luisa; Catalano, Dario; Scavo, Emanuela; Nicotra, Annalisa; Benfante, Antonina; Pistone, Giuseppe; Caputo, Valentina; Dieli, Francesco; Pirrello, Roberto; Stassi, Giorgio

    2017-10-23

    The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic-phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc patients. The adipose tissue-derived cell fraction, the so-called stromal vascular fraction (SVF), was coinjected with PRP in the perioral area of SSc patients. Histopathological and phenotypical analysis of adipose tissue from SSc patients revealed a disorganization of its distinct architecture coupled with an altered cell composition. Although AD-MSCs derived from SSc patients showed high multipotency, they failed to sustain a terminally differentiated progeny. Furthermore, SVFs derived from SSc patients differed from healthy donors in their MSC-like traits coupled with an aberrant cytokine production profile. Finally, the administration of PRP in combination with autologous SVF improved buccal's rhyme, skin elasticity and vascularization for all of the SSc patients enrolled in this study. This innovative regenerative therapy could be exploited for the treatment of chronic connective tissue diseases, including SSc.

  5. Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients

    Directory of Open Access Journals (Sweden)

    Francesco Virzì

    2017-10-01

    Full Text Available Abstract Background The use of stem cells, including mesenchymal stem cells (MSCs, for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP to improve the clinical outcome of patients affected by systemic sclerosis (SSc. Methods Adipose-derived mesenchymal stem cells (AD-MSCs and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic–phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc patients. The adipose tissue-derived cell fraction, the so-called stromal vascular fraction (SVF, was coinjected with PRP in the perioral area of SSc patients. Results Histopathological and phenotypical analysis of adipose tissue from SSc patients revealed a disorganization of its distinct architecture coupled with an altered cell composition. Although AD-MSCs derived from SSc patients showed high multipotency, they failed to sustain a terminally differentiated progeny. Furthermore, SVFs derived from SSc patients differed from healthy donors in their MSC-like traits coupled with an aberrant cytokine production profile. Finally, the administration of PRP in combination with autologous SVF improved buccal’s rhyme, skin elasticity and vascularization for all of the SSc patients enrolled in this study. Conclusions This innovative regenerative therapy could be exploited for the treatment of chronic connective tissue diseases, including SSc.

  6. Fractional derivative and its application in mathematics and physics

    International Nuclear Information System (INIS)

    Namsrai, K.

    2004-12-01

    We propose fractional derivatives and to study those mathematical and physical consequences. It is shown that fractional derivatives possess noncommutative and nonassociative properties and within which motion of a particle, differential and integral calculuses are investigated. (author)

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  8. Chondrogenesis of adipose-derived adult stem cells in a poly-lactide-co-glycolide scaffold

    DEFF Research Database (Denmark)

    Mehlhorn, Alexander T; Zwingmann, Jorn; Finkenzeller, Guenter

    2009-01-01

    Adult adipose-derived stem cells (ASCs) are considered to be an alternative cell source for cell-based cartilage repair because of their multiple differentiation potentials. This article addresses the chondrogenic differentiation of ASCs seeded into poly-lactide-co-glycolide (PLGA) scaffolds after...

  9. Spatial Rotation of the Fractional Derivative in Two-Dimensional Space

    Directory of Open Access Journals (Sweden)

    Ehab Malkawi

    2015-01-01

    Full Text Available The transformations of the partial fractional derivatives under spatial rotation in R2 are derived for the Riemann-Liouville and Caputo definitions. These transformation properties link the observation of physical quantities, expressed through fractional derivatives, with respect to different coordinate systems (observers. It is the hope that such understanding could shed light on the physical interpretation of fractional derivatives. Also it is necessary to be able to construct interaction terms that are invariant with respect to equivalent observers.

  10. Geometrical explanation of the fractional complex transform and derivative chain rule for fractional calculus

    International Nuclear Information System (INIS)

    He, Ji-Huan; Elagan, S.K.; Li, Z.B.

    2012-01-01

    The fractional complex transform is suggested to convert a fractional differential equation with Jumarie's modification of Riemann–Liouville derivative into its classical differential partner. Understanding the fractional complex transform and the chain rule for fractional calculus are elucidated geometrically. -- Highlights: ► The chain rule for fractional calculus is invalid, a counter example is given. ► The fractional complex transform is explained geometrically. ► Fractional equations can be converted into differential equations.

  11. Fractional derivatives. An introduction; Derivate frazionarie. Che cosa sono, a cosa servono

    Energy Technology Data Exchange (ETDEWEB)

    Dattoli, G. [ENEA, Div. Fisica Applicata, Centro Ricerche Frascati, Rome (Italy)

    2001-07-01

    In this item is presented a brief survey of fractional calculus and of the relevant applications. In the work are discussed different points of view of the operation of fractional derivative and present a unifying definition. The role played by fractional derivatives and integrals within the framework of integral transform is analyzed. [Italian] In questo articolo si traccia un profilo del cosidetto calcolo frazionario e delle relative applicazioni a problemi di matematica pura ed applicata. Si discutono varie definizioni dell'operazione di derivata frazionaria, non tutte coincidenti fra loro, e si mostra come sia possibile proporre una definizione univoca che inglobi tutte le altre. Si analizza infine il ruolo giocato dalle derivate e dagli integrali frazionari e, piu' in generale, quello degli operatori differenziali ad esponente frazionario, nell'ambito della teoria delle rappresentazioni integrali.

  12. Exact solutions to the time-fractional differential equations via local fractional derivatives

    Science.gov (United States)

    Guner, Ozkan; Bekir, Ahmet

    2018-01-01

    This article utilizes the local fractional derivative and the exp-function method to construct the exact solutions of nonlinear time-fractional differential equations (FDEs). For illustrating the validity of the method, it is applied to the time-fractional Camassa-Holm equation and the time-fractional-generalized fifth-order KdV equation. Moreover, the exact solutions are obtained for the equations which are formed by different parameter values related to the time-fractional-generalized fifth-order KdV equation. This method is an reliable and efficient mathematical tool for solving FDEs and it can be applied to other non-linear FDEs.

  13. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

    Directory of Open Access Journals (Sweden)

    Shengchang Zhang

    Full Text Available INTRODUCTION: Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. MATERIALS AND METHODS: Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP-expressing ASCs, aminoguanidine (AG or phosphate-buffered saline (PBS. Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD and malondialdehyde (MDA. RESULTS: Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. CONCLUSIONS: These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

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

    Science.gov (United States)

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

    2016-05-01

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

  15. Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

    NARCIS (Netherlands)

    Kanhai, D.A.N.I.S.

    2013-01-01

    Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society,

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

    Directory of Open Access Journals (Sweden)

    P. Bräunig

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

  17. A Caputo fractional derivative of a function with respect to another function

    Science.gov (United States)

    Almeida, Ricardo

    2017-03-01

    In this paper we consider a Caputo type fractional derivative with respect to another function. Some properties, like the semigroup law, a relationship between the fractional derivative and the fractional integral, Taylor's Theorem, Fermat's Theorem, etc., are studied. Also, a numerical method to deal with such operators, consisting in approximating the fractional derivative by a sum that depends on the first-order derivative, is presented. Relying on examples, we show the efficiency and applicability of the method. Finally, an application of the fractional derivative, by considering a Population Growth Model, and showing that we can model more accurately the process using different kernels for the fractional operator is provided.

  18. Fractional diffusion equation with distributed-order material derivative. Stochastic foundations

    International Nuclear Information System (INIS)

    Magdziarz, M; Teuerle, M

    2017-01-01

    In this paper, we present the stochastic foundations of fractional dynamics driven by the fractional material derivative of distributed-order type. Before stating our main result, we present the stochastic scenario which underlies the dynamics given by the fractional material derivative. Then we introduce the Lévy walk process of distributed-order type to establish our main result, which is the scaling limit of the considered process. It appears that the probability density function of the scaling limit process fulfills, in a weak sense, the fractional diffusion equation with the material derivative of distributed-order type. (paper)

  19. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

    DEFF Research Database (Denmark)

    Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene

    2017-01-01

    Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils...... in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability...... of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source...

  20. Generalized time fractional IHCP with Caputo fractional derivatives

    International Nuclear Information System (INIS)

    Murio, D A; MejIa, C E

    2008-01-01

    The numerical solution of the generalized time fractional inverse heat conduction problem (GTFIHCP) on a finite slab is investigated in the presence of measured (noisy) data when the time fractional derivative is interpreted in the sense of Caputo. The GTFIHCP involves the simultaneous identification of the heat flux and temperature transient functions at one of the boundaries of the finite slab together with the initial condition of the original direct problem from noisy Cauchy data at a discrete set of points on the opposite (active) boundary. A finite difference space marching scheme with adaptive regularization, using trigonometric mollification techniques and generalized cross validation is introduced. Error estimates for the numerical solution of the mollified problem and numerical examples are provided.

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

    OpenAIRE

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

    2013-01-01

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

  2. Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Umesh D. Wankhade

    2016-01-01

    Full Text Available Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT, it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell-based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future.

  3. Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Chan, Xin Yi; Black, Rebecca; Dickerman, Kayla; Federico, Joseph; Lévesque, Mathieu; Mumm, Jeff; Gerecht, Sharon

    2015-12-01

    In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient-derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC-derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells-expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-α. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering. © 2015 American Heart Association, Inc.

  4. Investigation of the Dirac Equation by Using the Conformable Fractional Derivative

    Science.gov (United States)

    Mozaffari, F. S.; Hassanabadi, H.; Sobhani, H.; Chung, W. S.

    2018-05-01

    In this paper,the Dirac equation is constructed using the conformable fractional derivative so that in its limit for the fractional parameter, the normal version is recovered. Then, the Cornell potential is considered as the interaction of the system. In this case, the wave function and the energy eigenvalue equation are derived with the aim of the bi-confluent Heun functions. use of the conformable fractional derivative is proven to lead to a branching treatment for the energy of the system. Such a treatment is obvious for small values of the fractional parameter, and a united value as the fractional parameter approaches unity.

  5. Autologous transplants of Adipose-Derived Adult Stromal (ADAS) afford dopaminergic neuroprotection in a model of Parkinson’s disease

    OpenAIRE

    McCoy, Melissa K.; Martinez, Terina N.; Ruhn, Kelly A.; Wrage, Philip C.; Keefer, Edward W.; Botterman, Barry R.; Tansey, Keith E.; Tansey, Malú G.

    2007-01-01

    Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned do...

  6. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  8. Development of large-scale manufacturing of adipose-derived stromal cells for clinical applications using bioreactors and human platelet lysate.

    Science.gov (United States)

    Haack-Sørensen, Mandana; Juhl, Morten; Follin, Bjarke; Harary Søndergaard, Rebekka; Kirchhoff, Maria; Kastrup, Jens; Ekblond, Annette

    2018-04-17

    In vitro expanded adipose-derived stromal cells (ASCs) are a useful resource for tissue regeneration. Translation of small-scale autologous cell production into a large-scale, allogeneic production process for clinical applications necessitates well-chosen raw materials and cell culture platform. We compare the use of clinical-grade human platelet lysate (hPL) and fetal bovine serum (FBS) as growth supplements for ASC expansion in the automated, closed hollow fibre quantum cell expansion system (bioreactor). Stromal vascular fractions were isolated from human subcutaneous abdominal fat. In average, 95 × 10 6 cells were suspended in 10% FBS or 5% hPL medium, and loaded into a bioreactor coated with cryoprecipitate. ASCs (P0) were harvested, and 30 × 10 6 ASCs were reloaded for continued expansion (P1). Feeding rate and time of harvest was guided by metabolic monitoring. Viability, sterility, purity, differentiation capacity, and genomic stability of ASCs P1 were determined. Cultivation of SVF in hPL medium for in average nine days, yielded 546 × 10 6 ASCs compared to 111 × 10 6 ASCs, after 17 days in FBS medium. ASCs P1 yields were in average 605 × 10 6 ASCs (PD [population doublings]: 4.65) after six days in hPL medium, compared to 119 × 10 6 ASCs (PD: 2.45) in FBS medium, after 21 days. ASCs fulfilled ISCT criteria and demonstrated genomic stability and sterility. The use of hPL as a growth supplement for ASCs expansion in the quantum cell expansion system provides an efficient expansion process compared to the use of FBS, while maintaining cell quality appropriate for clinical use. The described process is an obvious choice for manufacturing of large-scale allogeneic ASC products.

  9. Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

    OpenAIRE

    Kanhai, D.A.N.I.S.

    2013-01-01

    Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society, which is attributable to better disease awareness, better preventive strategies and better healthcare systems. As mortality rates are decreasing, the number of patients surviving their first vascul...

  10. Space-Time Fractional Diffusion-Advection Equation with Caputo Derivative

    Directory of Open Access Journals (Sweden)

    José Francisco Gómez Aguilar

    2014-01-01

    Full Text Available An alternative construction for the space-time fractional diffusion-advection equation for the sedimentation phenomena is presented. The order of the derivative is considered as 0<β, γ≤1 for the space and time domain, respectively. The fractional derivative of Caputo type is considered. In the spatial case we obtain the fractional solution for the underdamped, undamped, and overdamped case. In the temporal case we show that the concentration has amplitude which exhibits an algebraic decay at asymptotically large times and also shows numerical simulations where both derivatives are taken in simultaneous form. In order that the equation preserves the physical units of the system two auxiliary parameters σx and σt are introduced characterizing the existence of fractional space and time components, respectively. A physical relation between these parameters is reported and the solutions in space-time are given in terms of the Mittag-Leffler function depending on the parameters β and γ. The generalization of the fractional diffusion-advection equation in space-time exhibits anomalous behavior.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and physiological doses of bone morphogenetic protein-2

    Directory of Open Access Journals (Sweden)

    A Mehrkens

    2012-09-01

    Full Text Available Engineered osteogenic constructs for bone repair typically involve complex and costly processes for cell expansion. Adipose tissue includes mesenchymal precursors in large amounts, in principle allowing for an intraoperative production of osteogenic grafts and their immediate implantation. However, stromal vascular fraction (SVF cells from adipose tissue were reported to require a molecular trigger to differentiate into functional osteoblasts. The present study tested whether physiological doses of recombinant human BMP-2 (rhBMP-2 could induce freshly harvested human SVF cells to generate ectopic bone tissue. Enzymatically dissociated SVF cells from 7 healthy donors (1 x 106 or 4 x 106 were immediately embedded in a fibrin gel with or without 250 ng rhBMP-2, mixed with porous silicated calcium-phosphate granules (Actifuse®, Apatech (final construct size: 0.1 cm3 and implanted ectopically for eight weeks in nude mice. In the presence of rhBMP-2, SVF cells not only supported but directly contributed to the formation of bone ossicles, which were not observed in control cell-free, rhBMP-2 loaded implants. In vitro analysis indicated that rhBMP-2 did not involve an increase in the percentage of SVF cells recruited to the osteogenic lineage, but rather induced a stimulation of the osteoblastic differentiation of the committed progenitors. These findings confirm the feasibility of generating fully osteogenic grafts using an easily accessible autologous cell source and low amounts of rhBMP-2, in a timing compatible with an intraoperative schedule. The study warrants further investigation at an orthotopic site of implantation, where the delivery of rhBMP-2 could be bypassed thanks to the properties of the local milieu.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  14. Fractional derivatives for physicists and engineers background and theory

    CERN Document Server

    Uchaikin, Vladimir V

    2013-01-01

    The first derivative of a particle coordinate means its velocity, the second means its acceleration, but what does a fractional order derivative mean? Where does it come from, how does it work, where does it lead to? The two-volume book written on high didactic level answers these questions. Fractional Derivatives for Physicists and Engineers— The first volume contains a clear introduction into such a modern branch of analysis as the fractional calculus. The second develops a wide panorama of applications of the fractional calculus to various physical problems. This book recovers new perspectives in front of the reader dealing with turbulence and semiconductors, plasma and thermodynamics, mechanics and quantum optics, nanophysics and astrophysics.  The book is addressed to students, engineers and physicists, specialists in theory of probability and statistics, in mathematical modeling and numerical simulations, to everybody who doesn't wish to stay apart from the new mathematical methods becoming more and ...

  15. Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model.

    Science.gov (United States)

    Ha, Sungji; Park, Hyunjun; Mahmood, Usman; Ra, Jeong Chan; Suh, Yoo-Hun; Chang, Keun-A

    2017-01-15

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display co-occurring repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on valproic acid (VPA)-induced autism model mice. Human ASCs were injected into the neonatal pups (P2 or P3) intraventricularly and then we evaluated major behavior symptoms of ASD. VPA-treated mice showed increased repetitive behaviors, decreased social interactions and increased anxiety but these autistic behaviors were ameliorated through transplantation of hASCs. In addition, hASCs transplantation restored the alteration of phosphatase and tensin homolog (PTEN) expression and p-AKT/AKT ratio in the brains of VPA-induced ASD model mice. The decreased level of vascular endothelial growth factor (VEGF) and interleukin 10 (IL-10) by VPA were rescued in the brains of the hASC-injected VPA mice. With these results, we experimentally found hASCs' therapeutic effects on autistic phenotypes in a ASD model mice for the first time. This animal model system can be used to elucidate further mechanisms of therapeutic effects of hASCs in ASD. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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.

  17. 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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kedong, E-mail: Kedongsong@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Li, Liying; Yan, Xinyu; Zhang, Wen; Zhang, Yu [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Wang, Yiwei [Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW, 2139 (Australia); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China)

    2017-01-01

    In this study, the interaction of human adipose tissue-derived stem cells (ADSCs) with chitosan/β-glycerophosphate/collagen (C/GP/Co) hybrid hydrogel was test, followed by investigating the capability of engineered adipose tissue formation using this ADSCs seeded hydrogel. The ADSCs were harvested and mixed with a C/GP/Co hydrogel followed by a gelation at 37 °C and an in vitro culture. The results showed that the ADSCs within C/GP/Co hydrogels achieved a 30% of expansion over 7 days in culture medium and encapsulated cell in C/GP/Co hydrogel demonstrated a characteristic morphology with high viability over 5 days. C/GP/Co hydrogel were subcutaneous injected into SD-rats to assess the biocompatibility. The induced ADSCs-C/GP/Co hydrogel and non-induced ADSCs-C/GP/Co hydrogel were subcutaneously injected into nude mice for detecting potential of adipogenic differentiation. It has shown that C/GP/Co hydrogel were well tolerated in SD rats where they had persisted over 4 weeks post implantation. Histology analysis indicated that induced ADSCs-C/GP/Co hydrogel has a greater number of adipocytes and vascularized adipose tissues compared with non-induced ADSCs-C/GP/Co hydrogel. - Highlights: • The hydrogel scaffold was produced using chitosan, β-glycerophosphate and collagen. • This novel hydrogel is in liquid phase at low temperature and is gelatinized at 37 °C. • The new hydrogel provides ADSCs a favorable 3D environment with highly maintenance of proliferation and cytoactive. • ADSCs seeded hydrogel differentiated into adipose tissue, indicating favorable ability of adipogenesis. • This attractive property of C/GP/CO hydrogel points to its value as an excellent scaffold for tissue engineering.

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

    Directory of Open Access Journals (Sweden)

    Yun Li

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-18

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  1. 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.

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

    OpenAIRE

    Krähenbühl, S. M.

    2016-01-01

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

  3. Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

    Directory of Open Access Journals (Sweden)

    Magali Kouidhi

    2015-01-01

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

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

    Science.gov (United States)

    Titos, Esther; Clària, Joan

    2013-12-01

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

  5. Modeling of heat conduction via fractional derivatives

    Science.gov (United States)

    Fabrizio, Mauro; Giorgi, Claudio; Morro, Angelo

    2017-09-01

    The modeling of heat conduction is considered by letting the time derivative, in the Cattaneo-Maxwell equation, be replaced by a derivative of fractional order. The purpose of this new approach is to overcome some drawbacks of the Cattaneo-Maxwell equation, for instance possible fluctuations which violate the non-negativity of the absolute temperature. Consistency with thermodynamics is shown to hold for a suitable free energy potential, that is in fact a functional of the summed history of the heat flux, subject to a suitable restriction on the set of admissible histories. Compatibility with wave propagation at a finite speed is investigated in connection with temperature-rate waves. It follows that though, as expected, this is the case for the Cattaneo-Maxwell equation, the model involving the fractional derivative does not allow the propagation at a finite speed. Nevertheless, this new model provides a good description of wave-like profiles in thermal propagation phenomena, whereas Fourier's law does not.

  6. Stem cell-derived vascular endothelial cells and their potential application in regenerative medicine

    Science.gov (United States)

    Although a 'vascular stem cell' population has not been identified or generated, vascular endothelial and mural cells (smooth muscle cells and pericytes) can be derived from currently known pluripotent stem cell sources, including human embryonic stem cells and induced pluripotent stem cells. We rev...

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  11. 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.

  12. Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing.

    Science.gov (United States)

    Kaisang, Lin; Siyu, Wang; Lijun, Fan; Daoyan, Pan; Xian, Cory J; Jie, Shen

    2017-09-01

    Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2013-06-01

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

  14. Fractional derivative of the Hurwitz ζ-function and chaotic decay to zero

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    C. Cattani

    2016-01-01

    Full Text Available In this paper the fractional order derivative of a Dirichlet series, Hurwitz zeta function and Riemann zeta function is explicitly computed using the Caputo fractional derivative in the Ortigueira sense. It is observed that the obtained results are a natural generalization of the integer order derivative. Some interesting properties of the fractional derivative of the Riemann zeta function are also investigated to show that there is a chaotic decay to zero (in the Gaussian plane and a promising expression as a complex power series.

  15. Therapeutic Potential of Human Adipose-Derived Stem/Stromal Cell Microspheroids Prepared by Three-Dimensional Culture in Non-Cross-Linked Hyaluronic Acid Gel.

    Science.gov (United States)

    Mineda, Kazuhide; Feng, Jingwei; Ishimine, Hisako; Takada, Hitomi; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Kanayama, Koji; Kato, Harunosuke; Mashiko, Takanobu; Hashimoto, Ichiro; Nakanishi, Hideki; Kurisaki, Akira; Yoshimura, Kotaro

    2015-12-01

    Three-dimensional culture of mesenchymal stem/stromal cells for spheroid formation is known to enhance their therapeutic potential for regenerative medicine. Spheroids were prepared by culturing human adipose-derived stem/stromal cells (hASCs) in a non-cross-linked hyaluronic acid (HA) gel and compared with dissociated hASCs and hASC spheroids prepared using a nonadherent dish. Preliminary experiments indicated that a 4% HA gel was the most appropriate for forming hASC spheroids with a relatively consistent size (20-50 µm) within 48 hours. Prepared spheroids were positive for pluripotency markers (NANOG, OCT3/4, and SOX-2), and 40% of the cells were SSEA-3-positive, a marker of the multilineage differentiating stress enduring or Muse cell. In contrast with dissociated ASCs, increased secretion of cytokines such as hepatocyte growth factor was detected in ASC spheroids cultured under hypoxia. On microarray ASC spheroids showed upregulation of some pluripotency markers and downregulation of genes related to the mitotic cell cycle. After ischemia-reperfusion injury to the fat pad in SCID mice, local injection of hASC spheroids promoted tissue repair and reduced the final atrophy (1.6%) compared with that of dissociated hASCs (14.3%) or phosphate-buffered saline (20.3%). Part of the administered hASCs differentiated into vascular endothelial cells. ASC spheroids prepared in a HA gel contain undifferentiated cells with therapeutic potential to promote angiogenesis and tissue regeneration after damage. This study shows the therapeutic value of human adipose-derived stem cell spheroids prepared in hyarulonic acid gel. The spheroids have various benefits as an injectable cellular product and show therapeutic potential to the stem cell-depleted conditions such as diabetic chronic skin ulcer. ©AlphaMed Press.

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

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    MW Laschke

    2014-10-01

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

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

    International Nuclear Information System (INIS)

    Kakudo, Natsuko; Shimotsuma, Ayuko; Kusumoto, Kenji

    2007-01-01

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

  18. The small leucine-rich proteoglycan, biglycan, is highly expressed in adipose tissue of Psammomys obesus and is associated with obesity and type 2 diabetes

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    Bolton K

    2012-04-01

    Full Text Available Kristy Bolton1, David Segal1, Ken Walder1,21Metabolic Research Unit, School of Medicine, 2Institute for Technology, Research and Innovation, Deakin University, Waurn Ponds, Victoria, AustraliaAbstract: We have previously demonstrated that the small leucine-rich proteoglycan decorin may play a role in adipose tissue homeostasis and the pathophysiology of obesity. Biglycan is highly similar in structure to decorin, therefore we hypothesized it would have a similar expression profile and role to decorin in adipose tissue. Real time polymerase chain reaction was used to measure biglycan mRNA levels in adipose tissue from normal glucose tolerant and impaired glucose tolerant and type 2 diabetic (T2D Psammomys obesus. Biglycan mRNA was found to be highly expressed in adipose tissue, and gene expression was significantly higher in visceral compared to subcutaneous adipose tissue, with elevated levels in obese, T2D compared to lean normal glucose tolerant P. obesus (P < 0.04. Biglycan mRNA was predominantly expressed by stromal/vascular cells of fractionated adipose tissue (P = 0.023. Biglycan expression in adipose tissue, particularly in the obese state, was markedly upregulated. Collectively, our data suggest that the small leucine-rich proteoglycan family proteins biglycan and decorin may play a role in the development of obesity and T2D, possibly by facilitating expansion of adipose tissue mass.Keywords: biglycan, small leucine-rich proteoglycan, Psammomys obesus, adipose tissue, obesity, type 2 diabetes

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Science.gov (United States)

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

    2007-02-13

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

  1. Turbulence modeling with fractional derivatives: Derivation from first principles and initial results

    Science.gov (United States)

    Epps, Brenden; Cushman-Roisin, Benoit

    2017-11-01

    Fluid turbulence is an outstanding unsolved problem in classical physics, despite 120+ years of sustained effort. Given this history, we assert that a new mathematical framework is needed to make a transformative breakthrough. This talk offers one such framework, based upon kinetic theory tied to the statistics of turbulent transport. Starting from the Boltzmann equation and ``Lévy α-stable distributions'', we derive a turbulence model that expresses the turbulent stresses in the form of a fractional derivative, where the fractional order is tied to the transport behavior of the flow. Initial results are presented herein, for the cases of Couette-Poiseuille flow and 2D boundary layers. Among other results, our model is able to reproduce the logarithmic Law of the Wall in shear turbulence.

  2. Magnetic resonance imaging tracking of human adipose derived stromal cells within three-dimensional scaffolds for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    C Lalande

    2011-04-01

    Full Text Available For bone tissue engineering, human Adipose Derived Stem Cells (hADSCs are proposed to be associated with a scaffold for promoting bone regeneration. After implantation, cellularised scaffolds require a non-invasive method for monitoring their fate in vivo. The purpose of this study was to use Magnetic Resonance Imaging (MRI-based tracking of these cells, labelled with magnetic agents for in vivo longitudinal assessment. hADSCs were isolated from adipose tissue and labelled with USPIO-rhodamine (Ultrasmall SuperParamagnetic Iron Oxide. USPIO internalisation, absence of toxicity towards hADSCs, and osteogenic differentiation of the labelled cells were evaluated in standard culture conditions. Labelled cells were then seeded within a 3D porous polysaccharide-based scaffold and imaged in vitro using fluorescence microscopy and MRI. Cellularised scaffolds were implanted subcutaneously in nude mice and MRI analyses were performed from 1 to 28 d after implantation. In vitro, no effect of USPIO labelling on cell viability and osteogenic differentiation was found. USPIO were efficiently internalised by hADSCs and generated a high T2* contrast. In vivo MRI revealed that hADSCs remain detectable until 28 d after implantation and could migrate from the scaffold and colonise the area around it. These data suggested that this scaffold might behave as a cell carrier capable of both holding a cell fraction and delivering cells to the site of implantation. In addition, the present findings evidenced that MRI is a reliable technique to validate cell-seeding procedures in 3D porous scaffolds, and to assess the fate of hADSCs transplanted in vivo.

  3. Generalization of Fuzzy Laplace Transforms of Fuzzy Fractional Derivatives about the General Fractional Order n-1<β

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    Amal Khalaf Haydar

    2016-01-01

    Full Text Available The main aim in this paper is to use all the possible arrangements of objects such that r1 of them are equal to 1 and r2 (the others of them are equal to 2, in order to generalize the definitions of Riemann-Liouville and Caputo fractional derivatives (about order 0<βfractional derivatives about the general fractional order n-1<βfractional initial value problems (FFIVPs are solved using the above two generalizations.

  4. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  5. Applications of continuity and discontinuity of a fractional derivative of the wave functions to fractional quantum mechanics

    International Nuclear Information System (INIS)

    Dong Jianping; Xu Mingyu

    2008-01-01

    The space fractional Schroedinger equation with a finite square potential, periodic potential, and delta-function potential is studied in this paper. We find that the continuity or discontinuity condition of a fractional derivative of the wave functions should be considered to solve the fractional Schroedinger equation in fractional quantum mechanics. More parity states than those given by standard quantum mechanics for the finite square potential well are obtained. The corresponding energy equations are derived and then solved by graphical methods. We show the validity of Bloch's theorem and reveal the energy band structure for the periodic potential. The jump (discontinuity) condition for the fractional derivative of the wave function of the delta-function potential is given. With the help of the jump condition, we study some delta-function potential fields. For the delta-function potential well, an alternate expression of the wave function (the H function form of it was given by Dong and Xu [J. Math. Phys. 48, 072105 (2007)]) is obtained. The problems of a particle penetrating through a delta-function potential barrier and the fractional probability current density of the particle are also discussed. We study the Dirac comb and show the energy band structure at the end of the paper

  6. Differentiation and Application of Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Maguire, Eithne Margaret; Xiao, Qingzhong; Xu, Qingbo

    2017-11-01

    Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease. © 2017 American Heart Association, Inc.

  7. Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

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    Alexander RW

    2013-04-01

    Full Text Available Robert W Alexander,1 David Harrell2 1Department of Surgery, School of Medicine and Dentistry, University of Washington, Seattle, WA, USA; 2Harvest-Terumo Inc, Plymouth, MA, USA Objectives: Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG with use of disposable, microcannula systems. Design: Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results: Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion: Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-01

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

  10. 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.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    Marta Dossena

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    OpenAIRE

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

    2017-01-01

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

  15. Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.

    Directory of Open Access Journals (Sweden)

    Vladimir A Lizunov

    Full Text Available While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

  16. Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun Kit; Luo, Baiwen; Guneta, Vipra [School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Li, Liang; Foo, Selin Ee Min [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Dai, Yun; Tan, Timothy Thatt Yang [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459 (Singapore); Tan, Nguan Soon [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore); KK Research Centre, KK Women' s and Children' s Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore); Choong, Cleo, E-mail: cleochoong@ntu.edu.sg [School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); KK Research Centre, KK Women' s and Children' s Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore); Wong, Marcus Thien Chong [Plastic, Reconstructive & Aesthetic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433 (Singapore)

    2017-06-01

    Adipose tissue is a rich source of extracellular matrix (ECM) material that can be isolated by delipidating and decellularizing the tissue. However, the current delipidation and decellularization methods either involve tedious and lengthy processes or require toxic chemicals, which may result in the elimination of vital proteins and growth factors found in the ECM. Hence, an alternative delipidation and decellularization method for adipose tissue was developed using supercritical carbon dioxide (SC-CO{sub 2}) that eliminates the need of any harsh chemicals and also reduces the amount of processing time required. The resultant SC-CO{sub 2}-treated ECM material showed an absence of nuclear content but the preservation of key proteins such as collagen Type I, collagen Type III, collagen Type IV, elastin, fibronectin and laminin. In addition, other biological factors such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also retained. Subsequently, the resulting SC-CO{sub 2}-treated ECM material was used as a bioactive coating on tissue culture plastic (TCP). Four different cell types including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells and human monocytic leukemia cells (THP-1) were used in this study to show that the SC-CO{sub 2}-treated ECM coating can be potentially used for various biomedical applications. The SC-CO{sub 2}-treated ECM material showed improved cell-material interactions for all cell types tested. In addition, in vitro scratch wound assay using HaCaT cells showed that the presence of SC-CO{sub 2}-treated ECM material enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1-derived macrophages showed that the SC-CO{sub 2}-treated ECM material did not evoke pro-inflammatory responses from the THP-1-derived macrophages. Overall

  17. 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

  18. Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue

    International Nuclear Information System (INIS)

    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

    2017-01-01

    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

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

    NARCIS (Netherlands)

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

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

  20. Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.

    Directory of Open Access Journals (Sweden)

    XiYou Wang

    Full Text Available The aim of the present study was to examine whether hypoxia preconditioning could improve therapeutic effects of adipose derived mesenchymal stem cells (AMSCs for diabetes induced erectile dysfunction (DED. AMSCs were pretreated with normoxia (20% O2, N-AMSCs or sub-lethal hypoxia (1% O2, H-AMSCs. The hypoxia exposure up-regulated the expression of several angiogenesis and neuroprotection related cytokines in AMSCs, including vascular endothelial growth factor (VEGF and its receptor FIK-1, angiotensin (Ang-1, basic fibroblast growth factor (bFGF, brain-derived neurotrophic factor (BDNF, glial cell-derived neurotrophic factor (GDNF, stromal derived factor-1 (SDF-1 and its CXC chemokine receptor 4 (CXCR4. DED rats were induced via intraperitoneal injection of streptozotocin (60 mg/kg and were randomly divided into three groups-Saline group: intracavernous injection with phosphate buffer saline; N-AMSCs group: N-AMSCs injection; H-AMSCs group: H-AMSCs injection. Ten rats without any treatment were used as normal control. Four weeks after injection, the mean arterial pressure (MAP and intracavernosal pressure (ICP were measured. The contents of endothelial, smooth muscle, dorsal nerve in cavernoursal tissue were assessed. Compared with N-AMSCs and saline, intracavernosum injection of H-AMSCs significantly raised ICP and ICP/MAP (p<0.05. Immunofluorescent staining analysis demonstrated that improved erectile function by MSCs was significantly associated with increased expression of endothelial markers (CD31 and vWF (p<0.01 and smooth muscle markers (α-SMA (p<0.01. Meanwhile, the expression of nNOS was also significantly higher in rats receiving H-AMSCs injection than those receiving N-AMSCs or saline injection. The results suggested that hypoxic preconditioning of MSCs was an effective approach to enhance their therapeutic effect for DED, which may be due to their augmented angiogenesis and neuroprotection.

  1. Contact with existing adipose tissue is inductive for adipogenesis in matrigel.

    LENUS (Irish Health Repository)

    Kelly, John L

    2006-07-01

    The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft ( p < 0.01). Autografts with 1mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

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

    Directory of Open Access Journals (Sweden)

    CHENG Shao-wen

    2012-02-01

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

  3. Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis

    Directory of Open Access Journals (Sweden)

    Maria Elena Falomo

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts

    Directory of Open Access Journals (Sweden)

    Oscar Villa

    2015-03-01

    Full Text Available Enamel matrix derivative is used to promote periodontal regeneration during the corrective phase of the treatment of periodontal defects. Our main goal was to analyze the bioactivity of different molecular weight fractions of enamel matrix derivative. Enamel matrix derivative, a complex mixture of proteins, was separated into 13 fractions using size-exclusion chromatography and characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and liquid chromatography–electrospray ionization–tandem mass spectrometry. Human periodontal ligament fibroblasts were treated with either enamel matrix derivative or the different fractions. Proliferation and cytokine secretion to the cell culture medium were measured and compared to untreated cells. The liquid chromatography–electrospray ionization–tandem mass spectrometry analyses revealed that the most abundant peptides were amelogenin and leucine-rich amelogenin peptide related. The fractions containing proteins above 20 kDa induced an increase in vascular endothelial growth factor and interleukin-6 secretion, whereas lower molecular weight fractions enhanced proliferation and secretion of interleukin-8 and monocyte chemoattractant protein-1 and reduced interleukin-4 release. The various molecular components in the enamel matrix derivative formulation might contribute to reported effects on tissue regeneration through their influence on vascularization, the immune response, and chemotaxis.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Angelou Valerie

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Fatemi

    2014-09-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  14. Comparison of Adipose-Derived and Bone Marrow Mesenchymal Stromal Cells in a Murine Model of Crohn's Disease.

    Science.gov (United States)

    Xie, Minghao; Qin, Huabo; Luo, Qianxin; He, Xiaosheng; He, Xiaowen; Lan, Ping; Lian, Lei

    2017-01-01

    Mesenchymal stromal cells (MSCs) have been used in the treatment of Crohn's disease (CD) because of the immunomodulatory ability. The aim of this study was to investigate the therapeutic effect of adipose-derived MSCs (AD-MSCs) and to compare the therapeutic effect of AD-MSCs with that of bone marrow MSCs (BM-MSCs) in a murine model of CD. Murine colitis model of CD was created by trinitrobenzene sulfonic acid (TNBS). Twelve hours after treatment with TNBS, the mouse model was injected with MSCs intraperitoneally. Real-time polymerase chain reaction and immunohistochemistry staining were used to measure the expression levels of inflammatory cytokines in colonic tissues to investigate the therapeutic effect of AD-MSCs. The ten-day survival was recorded after infusion of MSCs. Intraperitoneal injection of MSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and improved the survival of the TNBS-induced mouse model of CD. AD-MSCs could effectively increase the expression of interleukin-10 and reduce the secretion of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor. The mucosal injury was repaired by AD-MSCs. These effects were comparable between AD-MSCs and BM-MSCs. The therapeutic effect appears similar between AD-MSCs and BM-MSCs in treating CD. AD-MSCs may be a potential alternative of cell-based therapy for CD.

  15. 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

  16. Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells

    NARCIS (Netherlands)

    Jin, S.; Hansson, E.M.; Tikka, S.; Lanner, F.; Sahlgren, C.; Farnebo, F.; Baumann, M.; Kalimo, H.; Lendahl, U.

    2008-01-01

    Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor

  17. 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.

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

    International Nuclear Information System (INIS)

    Silva Meirelles, Lindolfo da; Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana; Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre

    2016-01-01

    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.

  19. Influence of epidermal growth factor (EGF) and hydrocortisone on the co-culture of mature adipocytes and endothelial cells for vascularized adipose tissue engineering.

    Science.gov (United States)

    Huber, Birgit; Czaja, Alina Maria; Kluger, Petra Juliane

    2016-05-01

    The composition of vascularized adipose tissue is still an ongoing challenge as no culture medium is available to supply adipocytes and endothelial cells appropriately. Endothelial cell medium is typically supplemented with epidermal growth factor (EGF) as well as hydrocortisone (HC). The effect of EGF on adipocytes is discussed controversially. Some studies say it inhibits adipocyte differentiation while others reported of improved adipocyte lipogenesis. HC is known to have lipolytic activities, which might result in mature adipocyte dedifferentiation. In this study, we evaluated the influence of EGF and HC on the co-culture of endothelial cells and mature adipocytes regarding their cell morphology and functionality. We showed in mono-culture that high levels of HC promoted dedifferentiation and proliferation of mature adipocytes, whereas EGF seemed to have no negative influence. Endothelial cells kept their typical cobblestone morphology and showed a proliferation rate comparable to the control independent of EGF and HC concentration. In co-culture, HC promoted dedifferentiation of mature adipocytes, which was shown by a higher glycerol release. EGF had no negative impact on adipocyte morphology. No negative impact on endothelial cell morphology and functionality could be seen with reduced EGF and HC supplementation in co-culture with mature adipocytes. Taken together, our results demonstrate that reduced levels of HC are needed for co-culturing mature adipocytes and endothelial cells. In co-culture, EGF had no influence on mature adipocytes. Therefore, for the composition of vascularized adipose tissue constructs, the media with low levels of HC and high or low levels of EGF can be used. © 2016 International Federation for Cell Biology.

  20. PRELIMINARY CLINICAL RESULTS WITH LIPOASPIRATE STROMAL VASCULAR CELL FRACTION IN TREATMENT OF PATIENTS WITH KNEE OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    E. Ya. Shevela

    2017-01-01

    Full Text Available The paper presents results of clinical application of autologous stromal-vascular fraction (SVF cells in patients with degenerative osteoarthritis (OA of the knee, grade II and III (Kellgren–Lawrence scale.We recruited six patients with knee OA (3 men and 3 women; median age 64 years with mean disease duration of 7 years. All the patients were administered a single intra-articular injection of autologous nucleated SVF cells at an average dose of 16.8±0.9 × 106 per joint (a total of 11 joints. The patients did not experience any serious side effects (allergic, toxic or inflammatory related to the knee injection. Patient surveys at 1 month after SVF administration revealed a decrease in the severity of pain, as measured by a visual analog scale (VAS and a specialized 100-point scale KOOS (subscale "pain" (p < 0.05 on both scales. Moreover, the patients reported improvement in the joint functions and quality of life related to affected joints on a KOOS scale (p < 0.05. These positive clinical changes persisted during 6 month follow up. Significant improvements were noted in ultrasound findings, with increased thickness of the cartilage layer at 3 months (in 73% of cases and at 6 months (in 82%. Our pilot study demonstrated the safety and tolerability of intra-articular injection of autologous SVF cells in patients with moderate to severe OA. The results obtained also indicate a significant antiinflammatory effect of autologous adipose tissue SVF cells, which is manifested at the early stages of cell therapy. Our further investigations will be focused on exploring the SVF stimulatory effects on regeneration of damaged joints.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  2. Finite element formulation of viscoelastic sandwich beams using fractional derivative operators

    Science.gov (United States)

    Galucio, A. C.; Deü, J.-F.; Ohayon, R.

    This paper presents a finite element formulation for transient dynamic analysis of sandwich beams with embedded viscoelastic material using fractional derivative constitutive equations. The sandwich configuration is composed of a viscoelastic core (based on Timoshenko theory) sandwiched between elastic faces (based on Euler-Bernoulli assumptions). The viscoelastic model used to describe the behavior of the core is a four-parameter fractional derivative model. Concerning the parameter identification, a strategy to estimate the fractional order of the time derivative and the relaxation time is outlined. Curve-fitting aspects are focused, showing a good agreement with experimental data. In order to implement the viscoelastic model into the finite element formulation, the Grünwald definition of the fractional operator is employed. To solve the equation of motion, a direct time integration method based on the implicit Newmark scheme is used. One of the particularities of the proposed algorithm lies in the storage of displacement history only, reducing considerably the numerical efforts related to the non-locality of fractional operators. After validations, numerical applications are presented in order to analyze truncation effects (fading memory phenomena) and solution convergence aspects.

  3. 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.

  4. Application of fractional derivative with exponential law to bi-fractional-order wave equation with frictional memory kernel

    Science.gov (United States)

    Cuahutenango-Barro, B.; Taneco-Hernández, M. A.; Gómez-Aguilar, J. F.

    2017-12-01

    Analytical solutions of the wave equation with bi-fractional-order and frictional memory kernel of Mittag-Leffler type are obtained via Caputo-Fabrizio fractional derivative in the Liouville-Caputo sense. Through the method of separation of variables and Laplace transform method we derive closed-form solutions and establish fundamental solutions. Special cases with homogeneous Dirichlet boundary conditions and nonhomogeneous initial conditions, as well as for the external force are considered. Numerical simulations of the special solutions were done and novel behaviors are obtained.

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

    Directory of Open Access Journals (Sweden)

    Ha Min Sung

    2012-01-01

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

  6. Cell-derived microparticles in haemostasis and vascular medicine.

    Science.gov (United States)

    Burnier, Laurent; Fontana, Pierre; Kwak, Brenda R; Angelillo-Scherrer, Anne

    2009-03-01

    Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  10. Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments

    Directory of Open Access Journals (Sweden)

    P Karschnia

    2018-05-01

    Full Text Available The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO. Ad-MVF were isolated from green fluorescent protein (GFP+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

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

    Science.gov (United States)

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

    2013-09-05

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-15

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

  14. A fractional derivative approach to full creep regions in salt rock

    DEFF Research Database (Denmark)

    Zhou, H. W.; Wang, C. P.; Mishnaevsky, Leon

    2013-01-01

    Based on the definition of the constant-viscosity Abel dashpot, a new creep element, referred to as the variable-viscosity Abel dashpot, is proposed to characterize damage growth in salt rock samples during creep tests. Ultrasonic testing is employed to determine a formula of the variable viscosity...... coefficient, indicating that the change of the variable viscosity coefficient with the time meets a negative exponent law. In addition, by replacing the Newtonian dashpot in the classical Nishihara model with the variable-viscosity Abel dashpot, a damage-mechanism-based creep constitutive model is proposed...... on the basis of time-based fractional derivative. The analytic solution for the fractional-derivative creep constitutive model is presented. The parameters of the fractional derivative creep model are determined by the Levenberg–Marquardt method on the basis of the experimental results of creep tests on salt...

  15. Generation of a vascularized organoid using skeletal muscle as the inductive source.

    LENUS (Irish Health Repository)

    Messina, Aurora

    2005-09-01

    The technology required for creating an in vivo microenvironment and a neovasculature that can grow with and service new tissue is lacking, precluding the possibility of engineering complex three-dimensional organs. We have shown that when an arterio-venous (AV) loop is constructed in vivo in the rat groin, and placed inside a semisealed chamber, an extensive functional vasculature is generated. To test whether this unusually angiogenic environment supports the survival and growth of implanted tissue or cells, we inserted various preparations of rat and human skeletal muscle. We show that after 6 weeks incubation of muscle tissue, the chamber filled with predominantly well-vascularized recipient-derived adipose tissue, but some new donor-derived skeletal muscle and connective tissue were also evident. When primary cultured myoblasts were inserted into the chamber with the AV loop, they converted to mature striated muscle fibers. Furthermore, we identify novel adipogenesis-inducing properties of skeletal muscle. This represents the first report of a specific three-dimensional tissue grown on its own vascular supply.

  16. Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Biraja C. Dash

    2016-07-01

    Full Text Available There is an urgent need for an efficient approach to obtain a large-scale and renewable source of functional human vascular smooth muscle cells (VSMCs to establish robust, patient-specific tissue model systems for studying the pathogenesis of vascular disease, and for developing novel therapeutic interventions. Here, we have derived a large quantity of highly enriched functional VSMCs from human induced pluripotent stem cells (hiPSC-VSMCs. Furthermore, we have engineered 3D tissue rings from hiPSC-VSMCs using a facile one-step cellular self-assembly approach. The tissue rings are mechanically robust and can be used for vascular tissue engineering and disease modeling of supravalvular aortic stenosis syndrome. Our method may serve as a model system, extendable to study other vascular proliferative diseases for drug screening. Thus, this report describes an exciting platform technology with broad utility for manufacturing cell-based tissues and materials for various biomedical applications.

  17. 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

  18. Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

    Science.gov (United States)

    Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

    2016-07-01

    Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. WNT5A-JNK regulation of vascular insulin resistance in human obesity.

    Science.gov (United States)

    Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

    2016-12-01

    Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

  20. Improvement of hydrodenitrogenation (HDN) in co-refining of coal-derived liquid and petroleum fraction

    Energy Technology Data Exchange (ETDEWEB)

    Machida, M.; Ono, S. [Idemitsu Kosan Co. Ltd., Tokyo (Japan); Hattori, H. [Hokkaido University, Sapporo (Japan). Center for Advanced Research of Energy Technology

    1997-09-01

    The improvement in hydrodenitrogenation (HDN) of coal-derived liquids by co-refining with a petroleum fraction results principally from lowering the nitrogen content of the feedstock (coal-derived liquid) by blending with a nitrogen-free petroleum fraction. Effects of different fractions of coal-derived liquids on HDN and hydrodeoxygenation (HDO) were also examined. The HDN improvement by co-refining could be interpreted in terms of Langmuir-Hinshelwood mechanism. 38 refs., 3 figs., 3 tabs.

  1. From the Cover: Adipose tissue mass can be regulated through the vasculature

    Science.gov (United States)

    Rupnick, Maria A.; Panigrahy, Dipak; Zhang, Chen-Yu; Dallabrida, Susan M.; Lowell, Bradford B.; Langer, Robert; Judah Folkman, M.

    2002-08-01

    Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.

  2. Bifurcation analysis of a noisy vibro-impact oscillator with two kinds of fractional derivative elements

    Science.gov (United States)

    Yang, YongGe; Xu, Wei; Yang, Guidong

    2018-04-01

    To the best of authors' knowledge, little work was referred to the study of a noisy vibro-impact oscillator with a fractional derivative. Stochastic bifurcations of a vibro-impact oscillator with two kinds of fractional derivative elements driven by Gaussian white noise excitation are explored in this paper. We can obtain the analytical approximate solutions with the help of non-smooth transformation and stochastic averaging method. The numerical results from Monte Carlo simulation of the original system are regarded as the benchmark to verify the accuracy of the developed method. The results demonstrate that the proposed method has a satisfactory level of accuracy. We also discuss the stochastic bifurcation phenomena induced by the fractional coefficients and fractional derivative orders. The important and interesting result we can conclude in this paper is that the effect of the first fractional derivative order on the system is totally contrary to that of the second fractional derivative order.

  3. 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.

  4. 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.

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

  6. 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....

  7. 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 ...

  8. Determination of a closed-form solution for the multidimensional transport equation using a fractional derivative

    International Nuclear Information System (INIS)

    Zabadal, J.; Vilhena, M.T.; Segatto, C.F.; Pazos, R.P.Ruben Panta.

    2002-01-01

    In this work we construct a closed-form solution for the multidimensional transport equation rewritten in integral form which is expressed in terms of a fractional derivative of the angular flux. We determine the unknown order of the fractional derivative comparing the kernel of the integral equation with the one of the Riemann-Liouville definition of fractional derivative. We report numerical simulations

  9. Determination of a closed-form solution for the multidimensional transport equation using a fractional derivative

    Energy Technology Data Exchange (ETDEWEB)

    Zabadal, J. E-mail: jorge.zabadal@ufrgs.br; Vilhena, M.T. E-mail: vilhena@mat.ufrgs.br; Segatto, C.F. E-mail: cynthia@mat.ufrgs.br; Pazos, R.P.Ruben Panta. E-mail: rpp@mat.pucrgs.br

    2002-07-01

    In this work we construct a closed-form solution for the multidimensional transport equation rewritten in integral form which is expressed in terms of a fractional derivative of the angular flux. We determine the unknown order of the fractional derivative comparing the kernel of the integral equation with the one of the Riemann-Liouville definition of fractional derivative. We report numerical simulations.

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

    Science.gov (United States)

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

    2014-01-01

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

  11. A novel strategy of spine defect repair with a degradable bioactive scaffold preloaded with adipose-derived stromal cells.

    Science.gov (United States)

    Liang, Haixiang; Li, Xudong; Shimer, Adam L; Balian, Gary; Shen, Francis H

    2014-03-01

    demonstrated more bone formation than the control groups. Besides the bone formation period that occurred between 2 and 4 weeks in all groups, a second bone formation period was found to occur only in the groups that received cells with previous induction in vitro. This second period of significant bone formation happened simultaneously with collapsing of the scaffolds. It was then demonstrated histologically that vascularization early in the process and cooperation between host bone and implanted cells accompanied by collapse of the scaffold may be the factors that influence bone formation. This study not only provides a therapeutic strategy of using biomaterial for bone repair in the spine, but also may lead to a technological method for studying the relationship between implanted stem cells and host tissue. Adipose-derived stromal cells maintained in culture on a scaffold and treated with osteogenic induction with growth factor ex vivo could be used to enhance bone repair in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity.

    Directory of Open Access Journals (Sweden)

    Gregorio Chazenbalk

    Full Text Available INTRODUCTION: Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs, adipose stem cells (ASCs, and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes. RESEARCH DESIGN AND METHODS: Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes, CD14 and CD68 (ATMs, CD34 (ASCs, and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPα and PPARγ. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+ ATMs. RESULTS: Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPα and PPARγ gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+/CD68(+/DLK (+ cell spheres supported the interaction of ATMs, ASCs and preadipocytes. CONCLUSIONS: Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+/CD68(+/DLK(+ cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and

  13. Fractional Brownian motions via random walk in the complex plane and via fractional derivative. Comparison and further results on their Fokker-Planck equations

    International Nuclear Information System (INIS)

    Jumarie, Guy

    2004-01-01

    There are presently two different models of fractional Brownian motions available in the literature: the Riemann-Liouville fractional derivative of white noise on the one hand, and the complex-valued Brownian motion of order n defined by using a random walk in the complex plane, on the other hand. The paper provides a comparison between these two approaches, and in addition, takes this opportunity to contribute some complements. These two models are more or less equivalent on the theoretical standpoint for fractional order between 0 and 1/2, but their practical significances are quite different. Otherwise, for order larger than 1/2, the fractional derivative model has no counterpart in the complex plane. These differences are illustrated by an example drawn from mathematical finance. Taylor expansion of fractional order provides the expression of fractional difference in terms of finite difference, and this allows us to improve the derivation of Fokker-Planck equation and Kramers-Moyal expansion, and to get more insight in their relation with stochastic differential equations of fractional order. In the case of multi-fractal systems, the Fokker-Planck equation can be solved by using path integrals, and the fractional dynamic equations of the state moments of the stochastic system can be easily obtained. By combining fractional derivative and complex white noise of order n, one obtains a family of complex-valued fractional Brownian motions which exhibits long-range dependence. The conclusion outlines suggestions for further research, mainly regarding Lorentz transformation of fractional noises

  14. A comparison study of steady-state vibrations with single fractional-order and distributed-order derivatives

    Directory of Open Access Journals (Sweden)

    Duan Jun-Sheng

    2017-12-01

    Full Text Available We conduct a detailed study and comparison for the one-degree-of-freedom steady-state vibrations under harmonic driving with a single fractional-order derivative and a distributed-order derivative. For each of the two vibration systems, we consider the stiffness contribution factor and damping contribution factor of the term of fractional derivatives, the amplitude and the phase difference for the response. The effects of driving frequency on these response quantities are discussed. Also the influences of the order α of the fractional derivative and the parameter γ parameterizing the weight function in the distributed-order derivative are analyzed. Two cases display similar response behaviors, but the stiffness contribution factor and damping contribution factor of the distributed-order derivative are almost monotonic change with the parameter γ, not exactly like the case of single fractional-order derivative for the order α. The case of the distributed-order derivative provides us more options for the weight function and parameters.

  15. Substance P enhances proliferation and paracrine potential of adipose-derived stem cells in vitro

    International Nuclear Information System (INIS)

    Kim, Suna; Piao, Jiyuan; Son, Youngsook; Hong, Hyun Sook

    2017-01-01

    Stem cells have tremendous promise to treat intractable diseases. Notably, adipose-derived stem cells (ADSCs) are actively being investigated because of ease of sampling and high repopulation capacity in vitro. ADSCs can exert a therapeutic effect through differentiation and paracrine potential, and these actions have been proven in many diseases, including cutaneous and inflammatory diseases. Transplantation of ADSCs necessitates therapeutic quantities and thus, long term ex vivo culture of ADSCs. However, this procedure can impair the activity of ADSCs and provoke cellular senescence, leading to low efficacy in vivo. Accordingly, strategies to restore cellular activity and inhibit senescence of stem cells during ex vivo culture are needed for stem cell-based therapies. This study evaluated a potential supplementary role of Substance P (SP) in ADSC ex vivo culture. After confirming that the ADSC cell cycle was damaged by passage 6 (p6), ADSCs at p6 were cultured with SP, and their proliferation rates, cumulative cell numbers, cytokine profiles, and impact on T/endothelial cells were assessed. Long-term culture weakened proliferation ability and secretion of the cytokines, transforming growth factor-beta 1 (TGF-beta1), vascular endothelial growth factor (VEGF), and stromal cell derived factor-1 alpha (SDF-1alpha) in ADSCs. However, SP treatment reduced the population doubling time (PDT), enabling gain of a sufficient number of ADSCs at early passages. In addition, SP restored cytokine secretion, enhancing the ADSC-mediated paracrine effect on T cell and human umbilical vein endothelial cells (HUVECs). Taken together, these results suggest that SP can retain the therapeutic effect of ADSCs by elevating their proliferative and paracrine potential in ex vivo culture. - Highlights: • Long-term culture of ADSCs leads to cell senescence. • Paracrine potential of ADSC decreases as passage number increases. • SP enhances the weakened proliferation capacity of

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-15

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

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

    Science.gov (United States)

    Zhang, Rui; Rosen, Joseph M

    2018-05-01

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

  19. Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

    Directory of Open Access Journals (Sweden)

    Jun Yu

    Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-21

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

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

    International Nuclear Information System (INIS)

    Tavakolinejad, Alireza; Rabbani, Mohsen; Janmaleki, Mohsen

    2015-01-01

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

  2. Image-guided, Laser-based Fabrication of Vascular-derived Microfluidic Networks

    OpenAIRE

    Heintz, Keely A.; Mayerich, David; Slater, John H.

    2017-01-01

    This detailed protocol outlines the implementation of image-guided, laser-based hydrogel degradation for the fabrication of vascular-derived microfluidic networks embedded in PEGDA hydrogels. Here, we describe the creation of virtual masks that allow for image-guided laser control; the photopolymerization of a micromolded PEGDA hydrogel, suitable for microfluidic network fabrication and pressure head-driven flow; the setup and use of a commercially available laser scanning confocal microscope...

  3. Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

    Science.gov (United States)

    Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

    2015-12-01

    Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  6. Subrecoil laser cooling dynamics: a fractional derivative approach

    International Nuclear Information System (INIS)

    Uchaikin, Vladimir V; Sibatov, Renat T

    2009-01-01

    The subrecoil laser cooling process is considered in the framework of a model with two states (trapping and recycling), with instantaneous transitions between them. The key point of the work is the use of a fractional exponential function for waiting time distributions. This allows us to derive a general master equation covering both important cases: those with exponential and power type tails. Their solutions are expressed through fractionally stable distributions. The pdfs of the total trapping time of an atom and the proportion of trapped atoms are found. Analytical relationships show a good agreement with numerical results from Monte Carlo simulation

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

    Directory of Open Access Journals (Sweden)

    Sankaralakshmi Gomathysankar

    2014-09-01

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

  8. Exact solutions of a class of fractional Hamiltonian equations involving Caputo derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Baleanu, Dumitru [Department of Mathematics and Computer Sciences, Faculty of Arts and Sciences, Cankaya University, Ankara 06530 (Turkey); Trujillo, Juan J [Departamento de Analisis Matematico, University of La Laguna, 38271 La Laguna, Tenerife (Spain)], E-mail: dumitru@cankaya.edu.tr, E-mail: JTrujill@ullmat.es, E-mail: baleanu@venus.nipne.ro

    2009-11-15

    The fractional Hamiltonian equations corresponding to the Lagrangians of constrained systems within Caputo derivatives are investigated. The fractional phase space is obtained and the exact solutions of some constrained systems are obtained.

  9. Adipose-Derived Stem Cells Respond to Increased Osmolarities.

    Directory of Open Access Journals (Sweden)

    Urška Potočar

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

  10. Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

    Science.gov (United States)

    Park, Susanna S

    2016-04-01

    Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

  11. Subharmonic Resonance of Van Der Pol Oscillator with Fractional-Order Derivative

    Directory of Open Access Journals (Sweden)

    Yongjun Shen

    2014-01-01

    Full Text Available The subharmonic resonance of van der Pol (VDP oscillator with fractional-order derivative is studied by the averaging method. At first, the first-order approximate solutions are obtained by the averaging method. Then the definitions of equivalent linear damping coefficient (ELDC and equivalent linear stiffness coefficient (ELSC for subharmonic resonance are established, and the effects of the fractional-order parameters on the ELDC, the ELSC, and the dynamical characteristics of system are also analysed. Moreover, the amplitude-frequency equation and phase-frequency equation of steady-state solution for subharmonic resonance are established. The corresponding stability condition is presented based on Lyapunov theory, and the existence condition for subharmonic resonance (ECSR is also obtained. At last, the comparisons of the fractional-order and the traditional integer-order VDP oscillator are fulfilled by the numerical simulation. The effects of the parameters in fractional-order derivative on the steady-state amplitude, the amplitude-frequency curves, and the system stability are also studied.

  12. Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.

    Science.gov (United States)

    Volat, Fanny E; Pointud, Jean-Christophe; Pastel, Emilie; Morio, Béatrice; Sion, Benoit; Hamard, Ghislaine; Guichardant, Michel; Colas, Romain; Lefrançois-Martinez, Anne-Marie; Martinez, Antoine

    2012-11-01

    Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

  13. Improvement in the repair of defects in maxillofacial soft tissue in irradiated minipigs by a mixture of adipose-derived stem cells and platelet-rich fibrin.

    Science.gov (United States)

    Chen, Yuanzheng; Niu, Zhanguo; Xue, Yan; Yuan, Fukang; Fu, Yanjie; Bai, Nan

    2014-10-01

    To find out if adipose-derived stem cells (ASC) and platelet-rich fibrin (PRF), alone or combined, had any effect on the repair of maxillofacial soft tissue defects in irradiated minipigs, ASC were isolated, characterised, and expanded. Twenty female minipigs, the right parotid glands of which had been irradiated, were randomly divided into 4 groups of 5 each: those in the first group were injected with both ASC and PRF (combined group), the second group was injected with ASC alone (ASC group), the third group with PRF alone (PRF group), and the fourth group with phosphate buffer saline (PBS) (control group). Six months after the last injection, the size and depth of each defect were assessed, and subcutaneous tissues were harvested, stained with haematoxylin and eosin, and examined immunohistologically and for apoptosis. Expanded cells were successfully isolated and identified. Six months after injection the defects in the 3 treated groups were significantly smaller (p<0.001) and shallower (p<0.001) than those in the control group. Those in the combined group were the smallest and shallowest. Haematoxylin and eosin showed that the 3 treated groups contained more subcutaneous adipose tissue than the control group, and also had significantly greater vascular density (p<0.001) and fewer apoptotic cells (p<0.001). Both ASC and PRF facilitate the repair of defects in maxillofacial soft tissue in irradiated minipigs, and their combined use is more effective than their use as single agents. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  15. An inverse Sturm–Liouville problem with a fractional derivative

    KAUST Repository

    Jin, Bangti

    2012-05-01

    In this paper, we numerically investigate an inverse problem of recovering the potential term in a fractional Sturm-Liouville problem from one spectrum. The qualitative behaviors of the eigenvalues and eigenfunctions are discussed, and numerical reconstructions of the potential with a Newton method from finite spectral data are presented. Surprisingly, it allows very satisfactory reconstructions for both smooth and discontinuous potentials, provided that the order . α∈. (1,. 2) of fractional derivative is sufficiently away from 2. © 2012 Elsevier Inc.

  16. Fractional Klein-Gordon equation composed of Jumarie fractional derivative and its interpretation by a smoothness parameter

    Science.gov (United States)

    Ghosh, Uttam; Banerjee, Joydip; Sarkar, Susmita; Das, Shantanu

    2018-06-01

    Klein-Gordon equation is one of the basic steps towards relativistic quantum mechanics. In this paper, we have formulated fractional Klein-Gordon equation via Jumarie fractional derivative and found two types of solutions. Zero-mass solution satisfies photon criteria and non-zero mass satisfies general theory of relativity. Further, we have developed rest mass condition which leads us to the concept of hidden wave. Classical Klein-Gordon equation fails to explain a chargeless system as well as a single-particle system. Using the fractional Klein-Gordon equation, we can overcome the problem. The fractional Klein-Gordon equation also leads to the smoothness parameter which is the measurement of the bumpiness of space. Here, by using this smoothness parameter, we have defined and interpreted the various cases.

  17. Mast cell deficiency results in the accumulation of preadipocytes in adipose tissue in both obese and non-obese mice

    Directory of Open Access Journals (Sweden)

    Yasushi Ishijima

    2014-01-01

    Full Text Available Mast cells have been suggested to play key roles in adipogenesis. We herein show that the expression of preadipocyte, but not adipocyte, marker genes increases in the white adipose tissue of mast cell-deficient (KitW-sh/W-sh mice under both obese and non-obese conditions. In vitro culturing with adipogenic factors revealed increased adipocytes differentiated from the KitW-sh/W-sh stromal vascular fraction, suggesting the accumulation of preadipocytes. Moreover, the increased expression of preadipocyte genes was restored by mast cell reconstitution in the KitW-sh/W-sh mice. These results suggest positive effects of mast cells on the preadipocyte to adipocyte transition under both physiological and pathological conditions.

  18. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

    Science.gov (United States)

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer Mi; Doh, Kyung-Oh; Hui, Chi-Chung; Sung, Hoon-Ki

    2017-11-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

  19. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

    Science.gov (United States)

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer MI; Doh, Kyung-Oh; Hui, Chi-chung; Sung, Hoon-Ki

    2017-01-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders. PMID:29039412

  20. Comparing the Caputo, Caputo-Fabrizio and Atangana-Baleanu derivative with fractional order: Fractional cubic isothermal auto-catalytic chemical system

    Science.gov (United States)

    Saad, K. M.

    2018-03-01

    In this work we extend the standard model for a cubic isothermal auto-catalytic chemical system (CIACS) to a new model of a fractional cubic isothermal auto-catalytic chemical system (FCIACS) based on Caputo (C), Caputo-Fabrizio (CF) and Atangana-Baleanu in the Liouville-Caputo sense (ABC) fractional time derivatives, respectively. We present approximate solutions for these extended models using the q -homotopy analysis transform method ( q -HATM). We solve the FCIACS with the C derivative and compare our results with those obtained using the CF and ABC derivatives. The ranges of convergence of the solutions are found and the optimal values of h , the auxiliary parameter, are derived. Finally, these solutions are compared with numerical solutions of the various models obtained using finite differences and excellent agreement is found.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Exendin-4 in combination with adipose-derived stem cells promotes angiogenesis and improves diabetic wound healing.

    Science.gov (United States)

    Seo, Eunhui; Lim, Jae Soo; Jun, Jin-Bum; Choi, Woohyuk; Hong, In-Sun; Jun, Hee-Sook

    2017-02-15

    Diminished wound healing is a major complication of diabetes mellitus and can lead to foot ulcers. However, there are limited therapeutic methods to treat this condition. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, is known to have many beneficial effects on diabetes. In addition, mesenchymal stem cells are known to have wound healing effects. We investigated the effects of Ex-4 in combination with human adipose tissue-derived stem cells (ADSCs) on diabetic wound healing in a diabetic animal model. Diabetic db/db (blood glucose levels, >500 mg/dl) or C57BL/6 mice were subjected to wounding on the skin of the back. One day after wounding, each wound received ADSCs (2.5 × 10 5 cells) injected intradermally around the wound and/or Ex-4 (50 μl of 100 nM Ex-4) topically applied on the wound with a fine brush daily. Wound size was monitored and wound histology was examined. Human endothelial cells and keratinocyte cells were used to assess angiogenesis and vascular endothelial growth factor expression in vitro. Topical administration of Ex-4 or injection of ADSCs resulted in a rapid reduction of wound size in both diabetic and normoglycemic animals compared with vehicle treatment. Histological analysis also showed rapid skin reconstruction in Ex-4-treated or ADSC-injected wounds. A combination of Ex-4 and ADSCs showed a significantly better therapeutic effect over either treatment alone. In vitro angiogenesis assays showed that both Ex-4 and ADSC-conditioned media (CM) treatment improved migration, invasion and proliferation of human endothelial cells. ADSC-CM also increased migration and proliferation of human keratinocytes. In addition, both Ex-4 and ADSC-CM increased the expression of vascular endothelial growth factor. Co-culture with ADSCs increased migration and proliferation of these cells similar to that found after ADSC-CM treatment. We suggest that Ex-4 itself is effective for the treatment of diabetic skin wounds, and a combination of

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

    Science.gov (United States)

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

    2015-10-01

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

  5. A PEGylated platelet free plasma hydrogel based composite scaffold enables stable vascularization and targeted cell delivery for volumetric muscle loss.

    Science.gov (United States)

    Aurora, Amit; Wrice, Nicole; Walters, Thomas J; Christy, Robert J; Natesan, Shanmugasundaram

    2018-01-01

    Extracellular matrix (ECM) scaffolds are being used for the clinical repair of soft tissue injuries. Although improved functional outcomes have been reported, ECM scaffolds show limited tissue specific remodeling response with concomitant deposition of fibrotic tissue. One plausible explanation is the regression of blood vessels which may be limiting the diffusion of oxygen and nutrients across the scaffold. Herein we develop a composite scaffold as a vasculo-inductive platform by integrating PEGylated platelet free plasma (PFP) hydrogel with a muscle derived ECM scaffold (m-ECM). In vitro, adipose derived stem cells (ASCs) seeded onto the composite scaffold differentiated into two distinct morphologies, a tubular network in the hydrogel, and elongated structures along the m-ECM scaffold. The composite scaffold showed a high expression of ITGA5, ITGB1, and FN and a synergistic up-regulation of ang1 and tie-2 transcripts. The in vitro ability of the composite scaffold to provide extracellular milieu for cell adhesion and molecular cues to support vessel formation was investigated in a rodent volumetric muscle loss (VML) model. The composite scaffold delivered with ASCs supported robust and stable vascularization. Additionally, the composite scaffold supported increased localization of ASCs in the defect demonstrating its ability for localized cell delivery. Interestingly, ASCs were observed homing in the injured muscle and around the perivascular space possibly to stabilize the host vasculature. In conclusion, the composite scaffold delivered with ASCs presents a promising approach for scaffold vascularization. The versatile nature of the composite scaffold also makes it easily adaptable for the repair of soft tissue injuries. Decellularized extracellular matrix (ECM) scaffolds when used for soft tissue repair is often accompanied by deposition of fibrotic tissue possibly due to limited scaffold vascularization, which limits the diffusion of oxygen and nutrients

  6. A simple graphical method for deriving kinetics of repair from fractionated and protracted irradiations

    International Nuclear Information System (INIS)

    Scalliet, P.; Schueren, E. van der; Erfmann, R.K.L.; Landuyt, W.

    1988-01-01

    The authors present a method for the derivation of the time constant of repair from fractionated and protracted irradiations, using formulae based on those derived by Dale (1985) and Liversage (1969) establishing the correlation between the biological effects of low dose rate and acute fractionated irradiation. (UK)

  7. On a business cycle model with fractional derivative under narrow-band random excitation

    International Nuclear Information System (INIS)

    Lin, Zifei; Li, Jiaorui; Li, Shuang

    2016-01-01

    This paper analyzes the dynamics of a business cycle model with fractional derivative of order  α (0 < α < 1) subject to narrow-band random excitation, in which fractional derivative describes the memory property of the economic variables. Stochastic dynamical system concepts are integrated into the business cycle model for understanding the economic fluctuation. Firstly, the method of multiple scales is applied to derive the model to obtain the approximate analytical solution. Secondly, the effect of economic policy with fractional derivative on the amplitude of the economic fluctuation and the effect on stationary probability density are studied. The results show macroeconomic regulation and control can lower the stable amplitude of economic fluctuation. While in the process of equilibrium state, the amplitude is magnified. Also, the macroeconomic regulation and control improves the stability of the equilibrium state. Thirdly, how externally stochastic perturbation affects the dynamics of the economy system is investigated.

  8. Coronary CT Angiography Derived Fractional Flow Reserve

    DEFF Research Database (Denmark)

    Nørgaard, Bjarne Linde; Jensen, Jesper Møller; Blanke, Philipp

    2017-01-01

    Purpose of Review: To summarize the scientific basis of CT derived fractional flow reserve (FFRCT) and present an updated review on the evidence from clinical trials and real-world observational data Recent Findings: In prospective multicenter studies of patients with stable coronary artery disea...... of patients with stable CAD. The optimal FFRCT testing interpretation strategy, as well as the relative cost-efficiency of FFRCT against standard noninvasive functional testing, need further investigation....

  9. White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

    Science.gov (United States)

    Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

    2010-01-01

    The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

  10. Measurement of the perfusion fraction in brain tumors with intravoxel incoherent motion MR imaging: validation with histopathological vascular density in meningiomas.

    Science.gov (United States)

    Togao, Osamu; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Momosaka, Daichi; Yoshimoto, Koji; Kuga, Daisuke; Mizoguchi, Masahiro; Suzuki, Satoshi O; Iwaki, Toru; Van Cauteren, Marc; Iihara, Koji; Honda, Hiroshi

    2018-05-01

    To evaluate the quantification performance of the perfusion fraction (f) measured with intravoxel incoherent motion (IVIM) MR imaging in a comparison with the histological vascular density in meningiomas. 29 consecutive patients with meningioma (59.0 ± 16.8 years old, 8 males and 21 females) who underwent a subsequent surgical resection were examined with both IVIM imaging and a histopathological analysis. IVIM imaging was conducted using a single-shot SE-EPI sequence with 13 b-factors (0, 10, 20, 30, 50, 80, 100, 200, 300, 400, 600, 800, 1000 s mm - 2 ) at 3T. The perfusion fraction (f) was calculated by fitting the IVIM bi-exponential model. The 90-percentile f-value in the tumor region-of-interest (ROI) was defined as the maximum f-value (f-max). Histopathological vascular density (%Vessel) was measured on CD31-immunostainted histopathological specimens. The correlation and agreement between the f-values and %Vessel was assessed. The f-max (15.5 ± 5.5%) showed excellent agreement [intraclass correlation coefficient (ICC) = 0.754] and a significant correlation (r = 0.69, p < 0.0001) with the %Vessel (12.9 ± 9.4%) of the tumors. The Bland-Altman plot analysis showed excellent agreement between the f-max and %Vessel (bias, -2.6%; 95% limits of agreement, from -16.0 to 10.8%). The f-max was not significantly different among the histological subtypes of meningioma. An excellent agreement and a significant correlation were observed between the f-values and %Vessel. The f-value can be used as a noninvasive quantitative imaging measure to directly assess the vascular volume fraction in brain tumors. Advances in knowledge: The f-value measured by IVIM imaging showed a significant correlation and an excellent agreement with the histological vascular density in the meningiomas. The f-value can be used as a noninvasive and quantitative imaging measure to directly assess the volume fraction of capillaries in brain tumors.

  11. 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.

  12. Neutron organ dose and the influence of adipose tissue

    Science.gov (United States)

    Simpkins, Robert Wayne

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

  13. Senescence and quiescence in adipose-derived stromal cells: Effects of human platelet lysate, fetal bovine serum and hypoxia.

    Science.gov (United States)

    Søndergaard, Rebekka Harary; Follin, Bjarke; Lund, Lisbeth Drozd; Juhl, Morten; Ekblond, Annette; Kastrup, Jens; Haack-Sørensen, Mandana

    2017-01-01

    Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine serum (FBS) at normoxia. However, the low proliferation rates of FBS-expanded ASCs could be signs of senescence or quiescence. We aimed to determine the effects of hypoxia and hPL on the expansion of ASCs and whether FBS-expanded ASCs are senescent or quiescent. ASCs expanded in FBS or hPL at normoxia or hypoxia until passage 7 (P7), or in FBS until P5 followed by culture in hPL until P7, were evaluated by proliferation rates, cell cycle analyses, gene expression and β-galactosidase activity. hPL at normoxia and hypoxia enhanced proliferation rates and expression of cyclins, and decreased G0/G1 fractions and expression of p21 and p27, compared with FBS. The shift from FBS to hPL enhanced cyclin levels, decreased p21 and p27 levels and tended to decrease G0/G1 fractions. Hypoxia does not add to the effect of hPL during ASC expansion with regard to proliferation, cell cycle regulation and expression of cyclins, p21 and p27. hPL rejuvenates FBS-expanded ASCs with regard to cell cycle regulation and expression of cyclins, p21 and p27. This indicates a reversible arrest. Therefore, we conclude that ASCs expanded until P7 are not senescent regardless of culture conditions. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model.

    Science.gov (United States)

    Irons, Robin F; Cahill, Kevin W; Rattigan, Deviney A; Marcotte, Joseph H; Fromer, Marc W; Chang, Shaohua; Zhang, Ping; Behling, Eric M; Behling, Kathryn C; Caputo, Francis J

    2018-05-09

    The purpose of our study was to investigate the effect of adipose-derived stem cells (ASCs), endothelial-differentiated ASCs (EC/ASCs), and various conditioned media (CM) on wound healing in a diabetic swine model. We hypothesized that ASC-based therapies would accelerate wound healing. Diabetes was induced in four Yorkshire swine through intravenous injection of streptozotocin. ASCs were harvested from flank fat and cultured in either M199 or EGM-2 medium. A duplicate series of seven full-thickness dorsal wounds were surgically created on each swine. The wounds in the cellular treatment group underwent injection of low-dose or high-dose ASCs or EC/ASCs on day 0, with a repeat injection of one half of the initial dose on day 15. Wounds assigned to the topical CM therapy were covered with 2 mL of either serum-free M199 primed by ASCs or human umbilical vein endothelial cells every 3 days. Wounds were assessed at day 0, 10, 15, 20, and 28. The swine were sacrificed on day 28. ImageJ software was used to evaluate the percentage of wound healing. The wounded skin underwent histologic, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay examinations to evaluate markers of angiogenesis and inflammation. We found an increase in the percentage of wound closure rates in cell-based treatments and topical therapies at various points compared with the untreated control wounds (P swine model. Enhanced angiogenesis and immunomodulation might be key contributors to this process. The purpose of the present study was to translate the known beneficial effects of adipose-derived stem cells and associated conditioned medium therapy on diabetic wound healing to a large animal model. We demonstrated that stem cell and conditioned medium therapy significantly accelerate gross wound healing in diabetic swine, with data suggesting this might result from a decreased inflammatory response and increased angiogenesis. Copyright © 2018 Society for

  15. Functions of Müller cell-derived vascular endothelial growthfactor in diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Müller cells are macroglia and play many essentialroles as supporting cells in the retina. To respond topathological changes in diabetic retinopathy (DR), amajor complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascularendothelial growth factor (VEGF or VEGF-A). As VEGFis expressed by multiple retinal cell-types and Müllerglia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function ofVEGF or other globally expressed proteins produced byMüller cells. With the development of conditional genetargeting tools, it is now possible to dissect the functionof Müller cell-derived VEGF in vivo . By using conditionalgene targeting approach, we demonstrate that Müllerglia are a major source of retinal VEGF in diabetic miceand Müller cell-derived VEGF plays a significant role inthe alteration of protein expression and peroxynitration,which leads to retinal inflammation, neovascularization,vascular leakage, and vascular lesion, key pathologicalchanges in DR. Therefore, Müller glia are a potentialcellular target for the treatment of DR, a leading causeof blindness.

  16. Subcutaneous adipose tissue classification

    Directory of Open Access Journals (Sweden)

    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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  18. A Novel Operational Matrix of Caputo Fractional Derivatives of Fibonacci Polynomials: Spectral Solutions of Fractional Differential Equations

    Directory of Open Access Journals (Sweden)

    Waleed M. Abd-Elhameed

    2016-09-01

    Full Text Available Herein, two numerical algorithms for solving some linear and nonlinear fractional-order differential equations are presented and analyzed. For this purpose, a novel operational matrix of fractional-order derivatives of Fibonacci polynomials was constructed and employed along with the application of the tau and collocation spectral methods. The convergence and error analysis of the suggested Fibonacci expansion were carefully investigated. Some numerical examples with comparisons are presented to ensure the efficiency, applicability and high accuracy of the proposed algorithms. Two accurate semi-analytic polynomial solutions for linear and nonlinear fractional differential equations are the result.

  19. Isolation and characterization of biochar-derived organic matter fractions and their phenanthrene sorption.

    Science.gov (United States)

    Jin, Jie; Sun, Ke; Liu, Wei; Li, Shiwei; Peng, Xianqiang; Yang, Yan; Han, Lanfang; Du, Ziwen; Wang, Xiangke

    2018-05-01

    Chemical composition and pollutant sorption of biochar-derived organic matter fractions (BDOMs) are critical for understanding the long-term environmental significance of biochar. Phenanthrene (PHE) sorption by the humic acid-like (HAL) fractions isolated from plant straw- (PLABs) and animal manure-based (ANIBs) biochars, and the residue materials (RES) after HAL extraction was investigated. The HAL fraction comprised approximately 50% of organic carbon (OC) of the original biochars. Results of XPS and 13 C NMR demonstrated that the biochar-derived HAL fractions mainly consisted of aromatic clusters substituted by carboxylic groups. The CO 2 cumulative surface area of BDOMs excluding PLAB-derived RES fractions was obviously lower than that of corresponding biochars. The sorption nonlinearity of PHE by the fresh biochars was significantly stronger than that of the BDOM fractions, implying that the BDOM fractions were more chemically homogeneous. The BDOMs generally exhibited comparable or higher OC-normalized distribution coefficients (K oc ) of PHE than the original biochars. The PHE logK oc values of the fresh biochars correlated negatively with the micropore volumes due to steric hindrance effect. In contrast, a positive relationship between the sorption coefficients (K d ) of BDOMs and the micropore volumes was observed in this study, suggesting that pore filling could dominate PHE sorption by the BDOMs. The positive correlation between the PHE logK oc values of the HAL fractions and the aromatic C contents indicates that PHE sorption by the HAL fractions was regulated by aromatic domains. The findings of this study improve our knowledge of the evolution of biochar properties after application and its potential environmental impacts. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-03-01

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

  1. Adipose derived stem cells in radiotherapy injury: a new frontier

    Directory of Open Access Journals (Sweden)

    Lipi eShukla

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-05-05

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

  3. Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J; Astrup, A

    1985-01-01

    Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured...... as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA....../albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization....

  4. Effects of Human Adipose-Derived Stem Cells on the Survival of Rabbit Ear Composite Grafts

    Directory of Open Access Journals (Sweden)

    Chae Min Kim

    2017-09-01

    Full Text Available Background Composite grafts are frequently used for facial reconstruction. However, the unpredictability of the results and difficulties with large defects are disadvantages. Adipose-derived stem cells (ADSCs express several cytokines, and increase the survival of random flaps and fat grafts owing to their angiogenic potential. Methods This study investigated composite graft survival after ADSC injection. Circular chondrocutaneous composite tissues, 2 cm in diameter, from 15 New Zealand white rabbits were used. Thirty ears were randomly divided into 3 groups. In the experimental groups (1 and 2, ADSCs were subcutaneously injected 7 days and immediately before the operation, respectively. Similarly, phosphate-buffered saline was injected in the control group just before surgery in the same manner as in group 2. In all groups, chondrocutaneous composite tissue was elevated, rotated 90 degrees, and repaired in its original position. Skin flow was assessed using laser Doppler 1, 3, 6, 9, and 12 days after surgery. At 1 and 12 days after surgery, the viable area was assessed using digital photography; the rabbits were euthanized, and immunohistochemical staining for CD31 was performed to assess neovascularization. Results The survival of composite grafts increased significantly with the injection of ADSCs (P<0.05. ADSC injection significantly improved neovascularization based on anti-CD31 immunohistochemical analysis and vascular endothelial growth factor expression (P<0.05 in both group 1 and group 2 compared to the control group. No statistically significant differences in graft survival, anti-CD31 neovascularization, or microcirculation were found between groups 1 and 2. Conclusions Treatment with ADSCs improved the composite graft survival, as confirmed by the survival area and histological evaluation. The differences according to the injection timing were not significant.

  5. Design of quadrature mirror filter bank using Lagrange multiplier method based on fractional derivative constraints

    Directory of Open Access Journals (Sweden)

    B. Kuldeep

    2015-06-01

    Full Text Available Fractional calculus has recently been identified as a very important mathematical tool in the field of signal processing. Digital filters designed by fractional derivatives give more accurate frequency response in the prescribed frequency region. Digital filters are most important part of multi-rate filter bank systems. In this paper, an improved method based on fractional derivative constraints is presented for the design of two-channel quadrature mirror filter (QMF bank. The design problem is formulated as minimization of L2 error of filter bank transfer function in passband, stopband interval and at quadrature frequency, and then Lagrange multiplier method with fractional derivative constraints is applied to solve it. The proposed method is then successfully applied for the design of two-channel QMF bank with higher order filter taps. Performance of the QMF bank design is then examined through study of various parameters such as passband error, stopband error, transition band error, peak reconstruction error (PRE, stopband attenuation (As. It is found that, the good design can be obtained with the change of number and value of fractional derivative constraint coefficients.

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

    Directory of Open Access Journals (Sweden)

    Gayathri Subramanian

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Nonlinear analysis and analog simulation of a piezoelectric buckled beam with fractional derivative

    Science.gov (United States)

    Mokem Fokou, I. S.; Buckjohn, C. Nono Dueyou; Siewe Siewe, M.; Tchawoua, C.

    2017-08-01

    In this article, an analog circuit for implementing fractional-order derivative and a harmonic balance method for a vibration energy harvesting system under pure sinusoidal vibration source is proposed in order to predict the system response. The objective of this paper is to discuss the performance of the system with fractional derivative and nonlinear damping (μb). Bifurcation diagram, phase portrait and power spectral density (PSD) are provided to deeply characterize the dynamics of the system. These results are corroborated by the 0-1 test. The appearance of the chaotic vibrations reduces the instantaneous voltage. The pre-experimental investigation is carried out through appropriate software electronic circuit (Multisim). The corresponding electronic circuit is designed, exhibiting periodic and chaotic behavior, in accord with numerical simulations. The impact of fractional derivative and nonlinear damping is presented with detail on the output voltage and power of the system. The agreement between numerical and analytical results justifies the efficiency of the analytical technique used. In addition, by combining the harmonic excitation with the random force, the stochastic resonance phenomenon occurs and improves the harvested energy. It emerges from these results that the order of fractional derivative μ and nonlinear damping μb play an important role in the response of the system.

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

    Directory of Open Access Journals (Sweden)

    Aldana D. Gojanovich

    2018-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Kevin Dzobo

    2016-08-01

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

  11. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

    Directory of Open Access Journals (Sweden)

    Tinahones Francisco

    2012-04-01

    Full Text Available Abstract Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR. Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC and omentum (OM adipose tissues from morbidly obese patients (n = 26 with low (OB/L-IR (healthy obese and high (OB/H-IR degrees of IR, and lean controls (n = 17. Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  13. The influence of thiazolidinediones on adipogenesis in vitro and in vivo: potential modifiers of intramuscular adipose tissue deposition in meat animals.

    Science.gov (United States)

    Hausman, G J; Poulos, S P; Pringle, T D; Azain, M J

    2008-04-01

    Thiazolidinediones (TZD) are insulin sensitizing agents currently used for the treatment of type 2 diabetes and are widely used as adipogenic agents because they are ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), a key adipogenic transcription factor. In vivo and in vitro studies of TZD as potential modifiers of intramuscular or marbling adipogenesis are reviewed. Thiazolidinedione-induced adipogenesis has been reported in numerous cell culture systems, including rodent, human, bovine, and porcine adipose tissue stromal-vascular (S-V) cell cultures. Studies of porcine S-V cell cultures derived from semitendinosus muscle show that TZD can potentially modify intramuscular or marbling adipogenesis. Preadipocyte recruitment was TZD-dependent in muscle S-V cultures but TZD-independent in adipose S-V cultures. There appear to be differences between adipocytes in muscle and subcutaneous adipose tissue, reminiscent of differences observed in adipocytes from different adipose tissue depots. Troglitazone, a TZD, induces marbling adipogenesis without inhibiting myogenesis when cells are grown on laminin precoated culture dishes. Additionally, troglitazone treatment does not increase lipid content in porcine adipose tissue or muscle S-V cell cultures. Thiazolidinedione treatment increases lipid content of muscle in rodents and humans; however, rosiglitazone treatment for 49 d in pigs did not influence muscle lipid content and meat quality, but several significant changes in muscle fatty acid composition were observed. Although timing of treatment with TZD needs to be optimized, evidence suggests these compounds may enhance marbling deposition in swine.

  14. A Fast Implicit Finite Difference Method for Fractional Advection-Dispersion Equations with Fractional Derivative Boundary Conditions

    Directory of Open Access Journals (Sweden)

    Taohua Liu

    2017-01-01

    Full Text Available Fractional advection-dispersion equations, as generalizations of classical integer-order advection-dispersion equations, are used to model the transport of passive tracers carried by fluid flow in a porous medium. In this paper, we develop an implicit finite difference method for fractional advection-dispersion equations with fractional derivative boundary conditions. First-order consistency, solvability, unconditional stability, and first-order convergence of the method are proven. Then, we present a fast iterative method for the implicit finite difference scheme, which only requires storage of O(K and computational cost of O(Klog⁡K. Traditionally, the Gaussian elimination method requires storage of O(K2 and computational cost of O(K3. Finally, the accuracy and efficiency of the method are checked with a numerical example.

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

    Directory of Open Access Journals (Sweden)

    Sinead P Blaber

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

  16. A Semianalytical Solution of the Fractional Derivative Model and Its Application in Financial Market

    Directory of Open Access Journals (Sweden)

    Lina Song

    2018-01-01

    Full Text Available Fractional differential equation has been introduced to the financial theory, which presents new ideas and tools for the theoretical researches and the practical applications. In the work, an approximate semianalytical solution of the time-fractional European option pricing model is derived using the method of combining the enhanced technique of Adomian decomposition method with the finite difference method. And then the result is introduced in China’s financial market. The work makes every effort to test the feasibility of the fractional derivative model in the actual financial market.

  17. On a higher order multi-term time-fractional partial differential equation involving Caputo-Fabrizio derivative

    OpenAIRE

    Pirnapasov, Sardor; Karimov, Erkinjon

    2017-01-01

    In the present work we discuss higher order multi-term partial differential equation (PDE) with the Caputo-Fabrizio fractional derivative in time. We investigate a boundary value problem for fractional heat equation involving higher order Caputo-Fabrizio derivatives in time-variable. Using method of separation of variables and integration by parts, we reduce fractional order PDE to the integer order. We represent explicit solution of formulated problem in particular case by Fourier series.

  18. Adipose mesenchymal stem cells isolated after manual or water jet-assisted liposuction display similar properties

    Directory of Open Access Journals (Sweden)

    Claire eBony

    2016-01-01

    Full Text Available Mesenchymal stem or stromal cells (MSC are under investigation in many clinical trials for their therapeutic potential in a variety of diseases, including autoimmune and inflammatory disorders. One of the main sources of MSCs is the adipose tissue, which is mainly obtained by manual liposuction using a cannula linked to a syringe. However, in the last years, a number of devices for fat liposuction intended for clinical use have been commercialized but few papers have compared these procedures in terms of stromal vascular fraction (SVF or adipose stromal cells (ASC. The objective of the present study was to compare and qualify for clinical use the adipose stromal cells (ASC obtained from fat isolated with the manual or the Bodyjet® waterjet-assisted procedure. Although the initial number of cells after collagenase digestion was higher with the manual procedure, both the percentage of dead cells, the number of CFU-F and the phenotype of cells were identical in the SVF at isolation and in the ASC populations at day 14. We also showed that the osteogenic and adipogenic differentiation potentials of ASCs were identical between preparations while a slight but significant higher in vitro immunosuppressive effect was observed with ASCs isolated from fat removed with a cannula. The difference in the immunomodulatory effect between ASC populations was however not observed in vivo using the delayed-type hypersensitivity model. Our data therefore indicate that the procedure for fat liposuction does not impact the characteristics or the therapeutic function of ASCs.

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

    OpenAIRE

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yan-ting TANG

    2016-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Li Xiaojie

    2009-01-01

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

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-19

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  5. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

    Science.gov (United States)

    Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2018-06-01

    Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing

  6. 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.

  7. Positive solutions of fractional differential equations with derivative terms

    Directory of Open Access Journals (Sweden)

    Cuiping Cheng

    2012-11-01

    Full Text Available In this article, we are concerned with the existence of positive solutions for nonlinear fractional differential equation whose nonlinearity contains the first-order derivative, $$displaylines{ D_{0^+}^{alpha}u(t+f(t,u(t,u'(t=0,quad tin (0,1,; n-14 $ $(ninmathbb{N}$, $D_{0^+}^{alpha}$ is the standard Riemann-Liouville fractional derivative of order $alpha$ and $f(t,u,u':[0,1] imes [0,inftyimes(-infty,+infty o [0,infty$ satisfies the Caratheodory type condition. Sufficient conditions are obtained for the existence of at least one or two positive solutions by using the nonlinear alternative of the Leray-Schauder type and Krasnosel'skii's fixed point theorem. In addition, several other sufficient conditions are established for the existence of at least triple, n or 2n-1 positive solutions. Two examples are given to illustrate our theoretical results.

  8. Injectable biomaterials for adipose tissue engineering

    International Nuclear Information System (INIS)

    Young, D A; Christman, K L

    2012-01-01

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

  9. Response analysis of a class of quasi-linear systems with fractional derivative excited by Poisson white noise

    Science.gov (United States)

    Yang, Yongge; Xu, Wei; Yang, Guidong; Jia, Wantao

    2016-08-01

    The Poisson white noise, as a typical non-Gaussian excitation, has attracted much attention recently. However, little work was referred to the study of stochastic systems with fractional derivative under Poisson white noise excitation. This paper investigates the stationary response of a class of quasi-linear systems with fractional derivative excited by Poisson white noise. The equivalent stochastic system of the original stochastic system is obtained. Then, approximate stationary solutions are obtained with the help of the perturbation method. Finally, two typical examples are discussed in detail to demonstrate the effectiveness of the proposed method. The analysis also shows that the fractional order and the fractional coefficient significantly affect the responses of the stochastic systems with fractional derivative.

  10. Response analysis of a class of quasi-linear systems with fractional derivative excited by Poisson white noise

    International Nuclear Information System (INIS)

    Yang, Yongge; Xu, Wei; Yang, Guidong; Jia, Wantao

    2016-01-01

    The Poisson white noise, as a typical non-Gaussian excitation, has attracted much attention recently. However, little work was referred to the study of stochastic systems with fractional derivative under Poisson white noise excitation. This paper investigates the stationary response of a class of quasi-linear systems with fractional derivative excited by Poisson white noise. The equivalent stochastic system of the original stochastic system is obtained. Then, approximate stationary solutions are obtained with the help of the perturbation method. Finally, two typical examples are discussed in detail to demonstrate the effectiveness of the proposed method. The analysis also shows that the fractional order and the fractional coefficient significantly affect the responses of the stochastic systems with fractional derivative.

  11. Response analysis of a class of quasi-linear systems with fractional derivative excited by Poisson white noise

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yongge; Xu, Wei, E-mail: weixu@nwpu.edu.cn; Yang, Guidong; Jia, Wantao [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China)

    2016-08-15

    The Poisson white noise, as a typical non-Gaussian excitation, has attracted much attention recently. However, little work was referred to the study of stochastic systems with fractional derivative under Poisson white noise excitation. This paper investigates the stationary response of a class of quasi-linear systems with fractional derivative excited by Poisson white noise. The equivalent stochastic system of the original stochastic system is obtained. Then, approximate stationary solutions are obtained with the help of the perturbation method. Finally, two typical examples are discussed in detail to demonstrate the effectiveness of the proposed method. The analysis also shows that the fractional order and the fractional coefficient significantly affect the responses of the stochastic systems with fractional derivative.

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

    Science.gov (United States)

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

    2016-12-01

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

  13. Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography

    Science.gov (United States)

    Brooksby, Ben; Pogue, Brian W.; Jiang, Shudong; Dehghani, Hamid; Srinivasan, Subhadra; Kogel, Christine; Tosteson, Tor D.; Weaver, John; Poplack, Steven P.; Paulsen, Keith D.

    2006-06-01

    Magnetic resonance (MR)-guided near-infrared spectral tomography was developed and used to image adipose and fibroglandular breast tissue of 11 normal female subjects, recruited under an institutional review board-approved protocol. Images of hemoglobin, oxygen saturation, water fraction, and subcellular scattering were reconstructed and show that fibroglandular fractions of both blood and water are higher than in adipose tissue. Variation in adipose and fibroglandular tissue composition between individuals was not significantly different across the scattered and dense breast categories. Combined MR and near-infrared tomography provides fundamental molecular information about these tissue types with resolution governed by MR T1 images. hemoglobin | magnetic resonance imaging | water | fat | oxygen saturation

  14. Economical impact of plasma fractionation project in Iran on affordability of plasma-derived medicines.

    Science.gov (United States)

    Cheraghali, A M; Aboofazeli, R

    2009-12-01

    In Iran all transfusion services are concentrated under authority of one public and centralized transfusion organization which has created the opportunity of using plasma produced in its blood centers for fractionation. In 2008 voluntary and non remunerated Iranian donors donated 1.8 million units of blood. This indicates a 25/1000 donation index. After responding to the needs for fresh plasma and cryoprecipitate each year about 150000 L of recovered plasma are reserved for fractionation. In an attempt to improve both blood safety profile and availability and affordability of plasma derived medicines, Iran's national transfusion service has entered into a contract fractionation agreement for surplus of plasma produced from donated blood by voluntary non remunerated donors. In order to ensure safety of product produced, Iran has chosen to collaborate with international fractionators based in highly regulated countries. The main objective of this study was to evaluate the impact of contract plasma fractionation on the affordability of the plasma derived medicines in Iran. During 2006-2008, Iran's contract fractionation project was able to produce 46%, 18% and 6% of IVIG, Albumin and FVIII consumed in Iran's market, respectively. In contrary to IVIG and Albumin, due to fairly high consumption of FVIII in Iran, the role of fractionation project in meeting the needs to FVIII was not substantial. However, Iran's experience has shown that contract plasma fractionation, through direct and indirect effects on price of plasma derived medicines, could substantially improve availability and affordability of such products in national health care system.

  15. Effects of visceral adiposity on glycerol pathways in gluconeogenesis.

    Science.gov (United States)

    Neeland, Ian J; Hughes, Connor; Ayers, Colby R; Malloy, Craig R; Jin, Eunsook S

    2017-02-01

    To determine the feasibility of using oral 13 C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans. Obese (BMI ≥30kg/m 2 ) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n=3), low VAT-fasting (n=4), and high VAT-refed (n=2) groups. Participants ingested [U- 13 C 3 ] glycerol and blood samples were subsequently analyzed at multiple time points over 3h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U- 13 C 3 ] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using 13 C NMR analysis of glucose. Mixed linear models were used to compare 13 C enrichment in glucose between groups. Mean age, BMI, and baseline glucose were 49years, 40.1kg/m 2 , and 98mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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

  17. 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.

  18. Stochastic response of van der Pol oscillator with two kinds of fractional derivatives under Gaussian white noise excitation

    International Nuclear Information System (INIS)

    Yang Yong-Ge; Xu Wei; Sun Ya-Hui; Gu Xu-Dong

    2016-01-01

    This paper aims to investigate the stochastic response of the van der Pol (VDP) oscillator with two kinds of fractional derivatives under Gaussian white noise excitation. First, the fractional VDP oscillator is replaced by an equivalent VDP oscillator without fractional derivative terms by using the generalized harmonic balance technique. Then, the stochastic averaging method is applied to the equivalent VDP oscillator to obtain the analytical solution. Finally, the analytical solutions are validated by numerical results from the Monte Carlo simulation of the original fractional VDP oscillator. The numerical results not only demonstrate the accuracy of the proposed approach but also show that the fractional order, the fractional coefficient and the intensity of Gaussian white noise play important roles in the responses of the fractional VDP oscillator. An interesting phenomenon we found is that the effects of the fractional order of two kinds of fractional derivative items on the fractional stochastic systems are totally contrary. (paper)

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-30

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

  1. Convolution Theorem of Fractional Fourier Transformation Derived by Representation Transformation in Quantum Mechancis

    International Nuclear Information System (INIS)

    Fan Hongyi; Hao Ren; Lu Hailiang

    2008-01-01

    Based on our previous paper (Commun. Theor. Phys. 39 (2003) 417) we derive the convolution theorem of fractional Fourier transformation in the context of quantum mechanics, which seems a convenient and neat way. Generalization of this method to the complex fractional Fourier transformation case is also possible

  2. Osteogenesis of Adipose-Derived and Bone Marrow Stem Cells with Polycaprolactone/Tricalcium Phosphate and Three-Dimensional Printing Technology in a Dog Model of Maxillary Bone Defects

    Directory of Open Access Journals (Sweden)

    Jeong Woo Lee

    2017-09-01

    Full Text Available Bone graft material should possess sufficient porosity and permeability to allow integration with native tissue and vascular invasion, and must satisfy oxygen and nutrient transport demands. In this study, we have examined the use of three-dimensional (3D-printed polycaprolactone/tricalcium phosphate (PCL/TCP composite material in bone grafting, to estimate the scope of its potential application in bone surgery. Adipose-derived stem cells (ADSCs and bone marrow stem cells (BMSCs are known to enhance osteointegration. We hypothesized that a patient-specific 3D-printed solid scaffold could help preserve seeded ADSCs and BMSCs and enhance osteointegration. Diffuse osteogenic tissue formation was observed by micro-computed tomography with both stem cell types, and the ADSC group displayed similar osteogenesis compared to the BMSC group. In histological assessment, the scaffold pores showed abundant ossification in both groups. Reverse transcription polymerase chain reaction (RT-PCR showed that the BMSC group had higher expression of genes associated with ossification, and this was confirmed by Western blot analysis. The ADSC- and BMSC-seeded 3D-printed PCL/TCP scaffolds displayed promising enhancement of osteogenesis in a dog model of maxillary bone defects.

  3. Changes in adipose tissue stromal-vascular cells in primary culture due to porcine sera

    International Nuclear Information System (INIS)

    Jewell, D.E.; Hausman, G.J.

    1986-01-01

    This study was conducted to determine the response of rat stromal-vascular cells to pig sea. Sera were collected from unselected contemporary (lean) and high backfat thickness selected (obese) pigs. Sera from obese pigs were collected either by exsanguination or cannulation. sera from lean pigs during the growing phase (45 kg) and the fattening phase (100-110 kg) were collected. Stromal-vascular cells derived rom rat inguinal tissue were cultured on either 25 cm 2 flasks, collagen-coated coverslips or petri dishes. Cell proliferation was measured by [ 3 H]-thymidine incorporation during the fourth day of culture. Coverslip cultures were used for histochemical analysis. Petri dish cultures were used for analysis of Sn-glycerol-3-phosphate dehydrogenase (GPDH) activity. All cells were plated for 24 hours in media containing 10 fetal bovine sera. Test media contained 2.5, 5.0, 10.0% sera. Sera from obese pigs increased GPDH activity and fat cell production when compared to the lean controls. The increased concentration of sera increased esterase activity and lipid as measured with oil red O. The sera from obese pigs collected at slaughter stimulated more fat cell production than obese sera collected by cannulation. These studies show there are adipogenic factors in obese pigs sera which promote fat cell development in primary cell culture

  4. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

    Directory of Open Access Journals (Sweden)

    Michael Spencer

    Full Text Available Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily. These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01, and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2 (p = 0.02 in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

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

    Science.gov (United States)

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

    2012-03-01

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

  6. General solution of the Bagley-Torvik equation with fractional-order derivative

    Science.gov (United States)

    Wang, Z. H.; Wang, X.

    2010-05-01

    This paper investigates the general solution of the Bagley-Torvik equation with 1/2-order derivative or 3/2-order derivative. This fractional-order differential equation is changed into a sequential fractional-order differential equation (SFDE) with constant coefficients. Then the general solution of the SFDE is expressed as the linear combination of fundamental solutions that are in terms of α-exponential functions, a kind of functions that play the same role of the classical exponential function. Because the number of fundamental solutions of the SFDE is greater than 2, the general solution of the SFDE depends on more than two free (independent) constants. This paper shows that the general solution of the Bagley-Torvik equation involves actually two free constants only, and it can be determined fully by the initial displacement and initial velocity.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Fractional derivatives of constant and variable orders applied to anomalous relaxation models in heat transfer problems

    Directory of Open Access Journals (Sweden)

    Yang Xiao-Jun

    2017-01-01

    Full Text Available In this paper, we address a class of the fractional derivatives of constant and variable orders for the first time. Fractional-order relaxation equations of constants and variable orders in the sense of Caputo type are modeled from mathematical view of point. The comparative results of the anomalous relaxation among the various fractional derivatives are also given. They are very efficient in description of the complex phenomenon arising in heat transfer.

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

    Directory of Open Access Journals (Sweden)

    Marcela Fernandes

    2018-01-01

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

  10. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    Science.gov (United States)

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  11. Adipose tissue-derived stem cells in neural regenerative medicine.

    Science.gov (United States)

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

    2015-01-01

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

  12. A Modified Groundwater Flow Model Using the Space Time Riemann-Liouville Fractional Derivatives Approximation

    Directory of Open Access Journals (Sweden)

    Abdon Atangana

    2014-01-01

    Full Text Available The notion of uncertainty in groundwater hydrology is of great importance as it is known to result in misleading output when neglected or not properly accounted for. In this paper we examine this effect in groundwater flow models. To achieve this, we first introduce the uncertainties functions u as function of time and space. The function u accounts for the lack of knowledge or variability of the geological formations in which flow occur (aquifer in time and space. We next make use of Riemann-Liouville fractional derivatives that were introduced by Kobelev and Romano in 2000 and its approximation to modify the standard version of groundwater flow equation. Some properties of the modified Riemann-Liouville fractional derivative approximation are presented. The classical model for groundwater flow, in the case of density-independent flow in a uniform homogeneous aquifer is reformulated by replacing the classical derivative by the Riemann-Liouville fractional derivatives approximations. The modified equation is solved via the technique of green function and the variational iteration method.

  13. The G′G-expansion method using modified Riemann–Liouville derivative for some space-time fractional differential equations

    Directory of Open Access Journals (Sweden)

    Ahmet Bekir

    2014-09-01

    Full Text Available In this paper, the fractional partial differential equations are defined by modified Riemann–Liouville fractional derivative. With the help of fractional derivative and traveling wave transformation, these equations can be converted into the nonlinear nonfractional ordinary differential equations. Then G′G-expansion method is applied to obtain exact solutions of the space-time fractional Burgers equation, the space-time fractional KdV-Burgers equation and the space-time fractional coupled Burgers’ equations. As a result, many exact solutions are obtained including hyperbolic function solutions, trigonometric function solutions and rational solutions. These results reveal that the proposed method is very effective and simple in performing a solution to the fractional partial differential equation.

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

    Science.gov (United States)

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

    2018-04-01

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

  15. Virtual-Reality Simulator System for Double Interventional Cardiac Catheterization Using Fractional-Order Vascular Access Tracker and Haptic Force Producer

    Directory of Open Access Journals (Sweden)

    Guan-Chun Chen

    2015-01-01

    Full Text Available This study proposes virtual-reality (VR simulator system for double interventional cardiac catheterization (ICC using fractional-order vascular access tracker and haptic force producer. An endoscope or a catheter for diagnosis and surgery of cardiovascular disease has been commonly used in minimally invasive surgery. It needs specific skills and experiences for young surgeons or postgraduate year (PGY students to operate a Berman catheter and a pigtail catheter in the inside of the human body and requires avoiding damaging vessels. To improve the training in inserting catheters, a double-catheter mechanism is designed for the ICC procedures. A fractional-order vascular access tracker is used to trace the senior surgeons’ consoled trajectories and transmit the frictional feedback and visual feedback during the insertion of catheters. Based on the clinical feeling through the aortic arch, vein into the ventricle, or tortuous blood vessels, haptic force producer is used to mock the elasticity of the vessel wall using voice coil motors (VCMs. The VR establishment with surgeons’ consoled vessel trajectories and hand feeling is achieved, and the experimental results show the effectiveness for the double ICC procedures.

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

    Directory of Open Access Journals (Sweden)

    Camilla Siciliano

    2016-09-01

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

  17. 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

  18. Higher order multi-term time-fractional partial differential equations involving Caputo-Fabrizio derivative

    OpenAIRE

    Erkinjon Karimov; Sardor Pirnafasov

    2017-01-01

    In this work we discuss higher order multi-term partial differential equation (PDE) with the Caputo-Fabrizio fractional derivative in time. Using method of separation of variables, we reduce fractional order partial differential equation to the integer order. We represent explicit solution of formulated problem in particular case by Fourier series.

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

    Science.gov (United States)

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

    2015-12-01

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

  20. ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoxi, E-mail: xiaoxi.liu@uky.edu; Liu, Jingjing, E-mail: jingjing.liu0@gmail.com; Lester, Joshua D., E-mail: joshua.lester@uky.edu; Pijut, Sonja S., E-mail: srhee2@uky.edu; Graf, Gregory A., E-mail: Gregory.Graf@uky.edu

    2015-01-02

    Highlights: • We examined the D2 localization and the proteome of D2-containing compartment in mouse adipose tissue. • We confirmed the presence of D2 on a subcellular compartment that has typical structure as a microperoxisome. • We demonstrated the scarcity of peroxisome markers on D2-containing compartment. • The D2-containing compartment may be a subpopulation of peroxisome in mouse adipose tissue. • Proteomic data suggests potential association between D2-containing compartment and mitochondria and ER. - Abstract: ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER.

  1. Higher order multi-term time-fractional partial differential equations involving Caputo-Fabrizio derivative

    Directory of Open Access Journals (Sweden)

    Erkinjon Karimov

    2017-10-01

    Full Text Available In this work we discuss higher order multi-term partial differential equation (PDE with the Caputo-Fabrizio fractional derivative in time. Using method of separation of variables, we reduce fractional order partial differential equation to the integer order. We represent explicit solution of formulated problem in particular case by Fourier series.

  2. Depot-Specific Response of Adipose Tissue to Diet-Induced Inflammation: The Retinoid-Related Orphan Receptor α (RORα) Involved?

    Science.gov (United States)

    Kadiri, Sarah; Auclair, Martine; Capeau, Jacqueline; Antoine, Bénédicte

    2017-11-01

    Epididymal adipose tissue (EAT), a visceral fat depot, is more closely associated with metabolic dysfunction than inguinal adipose tissue (IAT), a subcutaneous depot. This study evaluated whether the nuclear receptor RORα, which controls inflammatory processes, could be implicated. EAT and IAT were compared in a RORα loss-of-function mouse (sg/sg) and in wild-type (WT) littermates, fed a standard diet (SD) or a Western diet (WD), to evaluate the impact of RORα expression on inflammatory status and on insulin sensitivity (IS) of each fat depot according to the diet. Sg/sg mice fed the SD exhibited a decreased inflammatory status and a higher IS in their fat depots than WT mice. WD-induced obesity had distinct effects on the two fat depots. In WT mice, EAT exhibited increased inflammation and insulin resistance while IAT showed reduced inflammation and improved IS, together with a depot-specific increase of RORα, and its target gene IκBα, in the stroma vascular fraction (SVF). Conversely, in sg/sg mice, WD increased inflammation and lowered IS of IAT but not of EAT. These findings suggest an anti-inflammatory role for RORα in response to WD, which occurs at the level of SVF of IAT, thus possibly contributing to the "healthy" expansion of IAT. © 2017 The Obesity Society.

  3. Effect of combined use of autologous adipose-derived stem cells and sterile biological films on chronic wound

    Directory of Open Access Journals (Sweden)

    Ming-hui LI

    2017-02-01

    Full Text Available Objective To analyze and evaluate the effectiveness of combined use of autologous adipose-derived stem cells (ADSCs and sterile biological films on chronic wound. Methods Sixty patients of chronic wound were selected from the General Hospital of Chinese People's Armed Police Forces, and randomly divided into three groups (20 each: the conventional treatment group (group A, the sterile biological films group (group B and ADSCs combined with sterile biological films group (group C. The wound healing time and healing rate of the 3 groups on 7, 21 and 40d after treatment were observed; The proliferation of the basilar membrane cells of wound epithelium in the 3 groups were observed before and 7, 14d after treatment, and the epithelization on 50d after treatment was also observed. The neonatal microvessel density (MVD in epidermal basal layer was calculated before and 7 days after treatment. Results On wound healing, the best result was shown in group C, manifested as the minor inflammatory response, the good formation of granulation tissue and faster speed in epithelial growth; and the result was better in group B than in group A. On wound healing time, the result was shown as group A > group B > group C, and the difference was statistically significant (P<0.05. On wound healing rate, cell proliferation and MVD, group C showed the best result in the 3 groups, group B was better than group A, and the differences were statistically significant (P<0.05. Conclusion ADSCs combined with sterile biological films in treatment of chronic wound healing may significantly improve the proliferation of repaired cells, promote wound vascular regeneration, improve the local growth environment and accelerate the wound healing. DOI: 10.11855/j.issn.0577-7402.2016.12.11

  4. Early childhood growth patterns and school-age respiratory resistance, fractional exhaled nitric oxide and asthma.

    Science.gov (United States)

    Casas, Maribel; den Dekker, Herman T; Kruithof, Claudia J; Reiss, Irwin K; Vrijheid, Martine; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

    2016-12-01

    Greater infant weight gain is associated with lower lung function and increased risk of childhood asthma. The role of early childhood peak growth patterns is unclear. We assessed the associations of individually derived early childhood peak growth patterns with respiratory resistance, fractional exhaled nitric oxide, wheezing patterns, and asthma until school-age. We performed a population-based prospective cohort study among 5364 children. Repeated growth measurements between 0 and 3 years of age were used to derive standard deviation scores (s.d.s) of peak height and weight velocities (PHV and PWV, respectively), and body mass index (BMI) and age at adiposity peak. Respiratory resistance and fractional exhaled nitric oxide were measured at 6 years of age. Wheezing patterns and asthma were prospectively assessed by annual questionnaires. We also assessed whether any association was explained by childhood weight status. Greater PHV was associated with lower respiratory resistance [Z-score (95% CI): -0.03 (-0.04, -0.01) per s.d.s increase] (n = 3382). Greater PWV and BMI at adiposity peak were associated with increased risks of early wheezing [relative risk ratio (95% CI): 1.11 (1.06, 1.16), 1.26 (1.11, 1.43), respectively] and persistent wheezing [relative risk ratio (95% CI): 1.09 (1.03, 1.16), 1.37 (1.17, 1.60), respectively] (n = 3189 and n = 3005, respectively). Childhood weight status partly explained these associations. No other associations were observed. PWV and BMI at adiposity peak are critical for lung developmental and risk of school-age wheezing. Follow-up studies at older ages are needed to elucidate whether these effects persist at later ages. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Marijana Todorčević

    2015-12-01

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

  6. Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity

    Science.gov (United States)

    Farb, Melissa G.; Tiwari, Stephanie; Karki, Shakun; Ngo, Doan TM; Carmine, Brian; Hess, Donald T.; Zuriaga, Maria A.; Walsh, Kenneth; Fetterman, Jessica L.; Hamburg, Naomi M.; Vita, Joseph A.; Apovian, Caroline M.; Gokce, Noyan

    2013-01-01

    Objective The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. Design and Methods In 20 obese subjects (age 37±12 yrs, BMI 47±8 kg/m2) we collected subcutaneous and visceral fat during bariatric surgery and characterized adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat. Results Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (p<0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway were upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by 2-fold (p=0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with Nω-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability. Conclusions Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity. PMID:23640904

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

    Directory of Open Access Journals (Sweden)

    Choi SY

    2015-07-01

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

  8. Linking the fractional derivative and the Lomnitz creep law to non-Newtonian time-varying viscosity

    Science.gov (United States)

    Pandey, Vikash; Holm, Sverre

    2016-09-01

    Many of the most interesting complex media are non-Newtonian and exhibit time-dependent behavior of thixotropy and rheopecty. They may also have temporal responses described by power laws. The material behavior is represented by the relaxation modulus and the creep compliance. On the one hand, it is shown that in the special case of a Maxwell model characterized by a linearly time-varying viscosity, the medium's relaxation modulus is a power law which is similar to that of a fractional derivative element often called a springpot. On the other hand, the creep compliance of the time-varying Maxwell model is identified as Lomnitz's logarithmic creep law, making this possibly its first direct derivation. In this way both fractional derivatives and Lomnitz's creep law are linked to time-varying viscosity. A mechanism which yields fractional viscoelasticity and logarithmic creep behavior has therefore been found. Further, as a result of this linking, the curve-fitting parameters involved in the fractional viscoelastic modeling, and the Lomnitz law gain physical interpretation.

  9. Fractional-order gradient descent learning of BP neural networks with Caputo derivative.

    Science.gov (United States)

    Wang, Jian; Wen, Yanqing; Gou, Yida; Ye, Zhenyun; Chen, Hua

    2017-05-01

    Fractional calculus has been found to be a promising area of research for information processing and modeling of some physical systems. In this paper, we propose a fractional gradient descent method for the backpropagation (BP) training of neural networks. In particular, the Caputo derivative is employed to evaluate the fractional-order gradient of the error defined as the traditional quadratic energy function. The monotonicity and weak (strong) convergence of the proposed approach are proved in detail. Two simulations have been implemented to illustrate the performance of presented fractional-order BP algorithm on three small datasets and one large dataset. The numerical simulations effectively verify the theoretical observations of this paper as well. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis.

    Science.gov (United States)

    Li, Naisi; Yang, Qiyuan; Walker, Ryan G; Thompson, Thomas B; Du, Min; Rodgers, Buel D

    2016-01-01

    A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle.

  11. On a system of differential equations with fractional derivatives arising in rod theory

    International Nuclear Information System (INIS)

    Atanackovic, Teodor M; Stankovic, Bogoljub

    2004-01-01

    We study a system of equations with fractional derivatives, that arises in the analysis of the lateral motion of an elastic column fixed at one end and loaded by a concentrated follower force at the other end. We assume that the column is positioned on a viscoelastic foundation described by a constitutive equation of fractional derivative type. The stability boundary is determined. It is shown that as in the case of an elastic (Winkler) type of foundation the stability boundary remains the same as for the column without a foundation! Thus, with the solution analysed here, the column exhibits the so-called Hermann-Smith paradox

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

    Directory of Open Access Journals (Sweden)

    Sherman Orye Canapp

    2016-09-01

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

  13. Method for the determination of the dominant eigenvalue of the neutron transport equation in a slab using fractional derivative

    International Nuclear Information System (INIS)

    Sperotto, Fabiola Aiub; Segatto, Cynthia Feijo; Zabadal, Jorge

    2002-01-01

    In this work, we determine the dominant eigenvalue of the one-dimensional neutron transport equation in a slab constructing an integral form for the neutron transport equation which is the expressed in terms of fractional derivative of the angular flux. Equating the fractional derivative of the angular flux to the integrate equation, we determine the unknown order of the fractional derivative comparing the kernel of the integral equation with the one of Riemann-Liouville definition of fractional derivative. Once known the angular flux the dominant eigenvalue is calculated solving a transcendental equation resulting from the application of the boundary conditions. We report the methodology applied, for comparison with available results in literature. (author)

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. Transplantation of Adipose Derived Stromal Cells into the Developing Mouse Eye

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  18. Tempered fractional calculus

    Energy Technology Data Exchange (ETDEWEB)

    Sabzikar, Farzad, E-mail: sabzika2@stt.msu.edu [Department of Statistics and Probability, Michigan State University, East Lansing, MI 48823 (United States); Meerschaert, Mark M., E-mail: mcubed@stt.msu.edu [Department of Statistics and Probability, Michigan State University, East Lansing, MI 48823 (United States); Chen, Jinghua, E-mail: cjhdzdz@163.com [School of Sciences, Jimei University, Xiamen, Fujian, 361021 (China)

    2015-07-15

    Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series.

  19. Tempered fractional calculus

    Science.gov (United States)

    Sabzikar, Farzad; Meerschaert, Mark M.; Chen, Jinghua

    2015-07-01

    Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series.

  20. Tempered fractional calculus

    International Nuclear Information System (INIS)

    Sabzikar, Farzad; Meerschaert, Mark M.; Chen, Jinghua

    2015-01-01

    Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series

  1. Modeling electro-magneto-hydrodynamic thermo-fluidic transport of biofluids with new trend of fractional derivative without singular kernel

    Science.gov (United States)

    Abdulhameed, M.; Vieru, D.; Roslan, R.

    2017-10-01

    This paper investigates the electro-magneto-hydrodynamic flow of the non-Newtonian behavior of biofluids, with heat transfer, through a cylindrical microchannel. The fluid is acted by an arbitrary time-dependent pressure gradient, an external electric field and an external magnetic field. The governing equations are considered as fractional partial differential equations based on the Caputo-Fabrizio time-fractional derivatives without singular kernel. The usefulness of fractional calculus to study fluid flows or heat and mass transfer phenomena was proven. Several experimental measurements led to conclusion that, in such problems, the models described by fractional differential equations are more suitable. The most common time-fractional derivative used in Continuum Mechanics is Caputo derivative. However, two disadvantages appear when this derivative is used. First, the definition kernel is a singular function and, secondly, the analytical expressions of the problem solutions are expressed by generalized functions (Mittag-Leffler, Lorenzo-Hartley, Robotnov, etc.) which, generally, are not adequate to numerical calculations. The new time-fractional derivative Caputo-Fabrizio, without singular kernel, is more suitable to solve various theoretical and practical problems which involve fractional differential equations. Using the Caputo-Fabrizio derivative, calculations are simpler and, the obtained solutions are expressed by elementary functions. Analytical solutions of the biofluid velocity and thermal transport are obtained by means of the Laplace and finite Hankel transforms. The influence of the fractional parameter, Eckert number and Joule heating parameter on the biofluid velocity and thermal transport are numerically analyzed and graphic presented. This fact can be an important in Biochip technology, thus making it possible to use this analysis technique extremely effective to control bioliquid samples of nanovolumes in microfluidic devices used for biological

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

    Science.gov (United States)

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

    2016-03-01

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

  3. Effects of exogenous oxygen derived free radicals on myocardial capillary permeability, vascular tone, and incidence of ventricular arrhythmias in the canine heart

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Bjerrum, P J

    1992-01-01

    The aim was to examine the effects of exogenous oxygen derived free radicals on myocardial capillary permeability for a small hydrophilic indicator, postischaemic vascular tone, and the occurrence of arrhythmias in the canine heart in vivo.......The aim was to examine the effects of exogenous oxygen derived free radicals on myocardial capillary permeability for a small hydrophilic indicator, postischaemic vascular tone, and the occurrence of arrhythmias in the canine heart in vivo....

  4. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2018-02-06

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

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

    Science.gov (United States)

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

    2012-08-01

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

  8. 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.

  9. Extended Riemann-Liouville type fractional derivative operator with applications

    Directory of Open Access Journals (Sweden)

    Agarwal P.

    2017-12-01

    Full Text Available The main purpose of this paper is to introduce a class of new extended forms of the beta function, Gauss hypergeometric function and Appell-Lauricella hypergeometric functions by means of the modified Bessel function of the third kind. Some typical generating relations for these extended hypergeometric functions are obtained by defining the extension of the Riemann-Liouville fractional derivative operator. Their connections with elementary functions and Fox’s H-function are also presented.

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

    Science.gov (United States)

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

    2015-04-15

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

  11. Analytical Solution for Fractional Derivative Gas-Flow Equation in Porous Media

    KAUST Repository

    El-Amin, Mohamed; Radwan, Ahmed G.; Sun, Shuyu

    2017-01-01

    In this paper, we introduce an analytical solution of the fractional derivative gas transport equation using the power-series technique. We present a new universal transform, namely, generalized Boltzmann change of variable which depends on the fractional order, time and space. This universal transform is employed to transfer the partial differential equation into an ordinary differential equation. Moreover, the convergence of the solution has been investigated and found that solutions are unconditionally converged. Results are introduced and discussed for the universal variable and other physical parameters such as porosity and permeability of the reservoir; time and space.

  12. Analytical Solution for Fractional Derivative Gas-Flow Equation in Porous Media

    KAUST Repository

    El-Amin, Mohamed

    2017-07-06

    In this paper, we introduce an analytical solution of the fractional derivative gas transport equation using the power-series technique. We present a new universal transform, namely, generalized Boltzmann change of variable which depends on the fractional order, time and space. This universal transform is employed to transfer the partial differential equation into an ordinary differential equation. Moreover, the convergence of the solution has been investigated and found that solutions are unconditionally converged. Results are introduced and discussed for the universal variable and other physical parameters such as porosity and permeability of the reservoir; time and space.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-02-01

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

  15. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

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

    OpenAIRE

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

    2015-01-01

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

  17. Analysis and application of diffusion equations involving a new fractional derivative without singular kernel

    Directory of Open Access Journals (Sweden)

    Lihong Zhang

    2017-11-01

    Full Text Available In this article, a family of nonlinear diffusion equations involving multi-term Caputo-Fabrizio time fractional derivative is investigated. Some maximum principles are obtained. We also demonstrate the application of the obtained results by deriving some estimation for solution to reaction-diffusion equations.

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

    Directory of Open Access Journals (Sweden)

    Marieta Costache

    2013-01-01

    Full Text Available Current clinical strategies for adipose tissue engineering (ATE, including autologous fat implants or the use of synthetic surrogates, not only are failing in the long term, but also can’t face the latest requirements regarding the aesthetic restoration of the resulted imperfections. In this context, modern strategies in current ATE applications are based on the implantation of 3D cell-scaffold bioconstructs, designed for prospective achievement of in situ functional de novo tissue. Thus, in this paper, we reported for the first time the evaluation of a spongious 60% collagen and 40% sericin