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Sample records for adipose stromal vascular

  1. Human Adipose Stromal Vascular Cell Delivery in a Fibrin Spray

    Zimmerlin, Ludovic; Rubin, J. Peter; Pfeifer, Melanie E.; Moore, L.R.; Donnenberg, Vera S.; Donnenberg, Albert D.

    2014-01-01

    Background Adipose tissue represents a practical source of autologous mesenchymal stromal cells (MSC) and vascular-endothelial progenitor cells, available for regenerative therapy without in vitro expansion. One of the problems confronting the therapeutic application of such cells is how to immobilize them at the wound site. Here, we evaluated in vitro the growth and differentiation of human adipose stromal vascular fraction (SVF) cells after delivery using a fibrin spray system. Methods SVF cells were harvested from four human adult patients undergoing elective abdominoplasty using the LipiVage™ system. After collagenase digestion, mesenchymal and endothelial progenitor cells (pericytes, supra-adventitial stromal cells, endothelial progenitors) were quantified by flow cytometry before culture. SVF cells were applied to culture vessels using the Tisseel™ fibrin spray system. SVF cell growth and differentiation was documented by immunofluorescence staining and photomicrography. Results SVF cells remained viable following application and were expanded up to three weeks, when they reached confluence and adipogenic differentiation. Under angiogenic conditions, SVF cells formed endothelial (vWF+, CD31+ and CD34+) tubules surrounded by CD146+ and α-SMA+ perivascular/stromal cells. Discussion Human adipose tissue is a rich source of autologous stem cells, which are readily available for regenerative applications such as wound healing, without in vitro expansion. Our results indicate that mesenchymal and endothelial progenitor cells, prepared in a closed system from unpassaged lipoaspirate samples, retain their growth and differentiation capacity when applied and immobilized on a substrate using a clinically approved fibrin sealant spray system. PMID:23260090

  2. Stromal vascular progenitors in adult human adipose tissue

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Pfeifer, Melanie E.; Meyer, E. Michael; Péault, Bruno; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    Background The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Methods Immunohistostaining of intact adipose tissue was used to identify 3 markers (CD31, CD34, CD146) which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90, CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture and tested for adipogenesis. Results The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/α-SMA+/CD90±/CD34−/CD31−; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146−/α-SMA−/CD90+/CD34+/CD31−. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), while small vessel endothelium was CD31+/CD34−/CD90− (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31− pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared to unsorted expanded SVF cells. Conclusions In adipose tissue perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34− pericytes, and the outermost of CD146−/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD

  3. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis

    Rodriguez Jorge; Alfaro Miguel; Lara Fabian; Solano Fabio; Wang Hao; Min Wei-Ping; Ichim Thomas E; Riordan Neil H; Harman Robert J; Patel Amit N; Murphy Michael P; Lee Roland R; Minev Boris

    2009-01-01

    Abstract The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects...

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

    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.

  5. Adipose-derived Stromal Cells Overexpressing Vascular Endothelial Growth Factor Accelerate Mouse Excisional Wound Healing

    Nauta, Allison; Seidel, Catharina; Deveza, Lorenzo; Montoro, Daniel; Grova, Monica; Ko, Sae Hee; Hyun, Jeong; Geoffrey C Gurtner; Longaker, Michael T.; Yang, Fan

    2012-01-01

    Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (β-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a c...

  6. Cryopreservation of stromal vascular fraction of adipose tissue in a serum-free freezing medium

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

    2010-01-01

    Developing effective techniques for the cryopreservation of human adipose-derived adult stem cells could increase the usefulness of these cells in tissue engineering and regenerative medicine. Unfortunately, the use of serum and a commonly used cryoprotectant chemical, dimethyl sulphoxide (DMSO), during cryopreservation storage restricts the direct translation of adult stem cells to in vivo applications. The objective of this study was to test the hypothesis that the stromal vascular fraction...

  7. Effects of Platelet-Rich Plasma, Adipose-Derived Stem Cells, and Stromal Vascular Fraction on the Survival of Human Transplanted Adipose Tissue

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

    2014-01-01

    Traditional adipose tissue transplantation has unpredictable viability and poor absorption rates. Recent studies have reported that treatment with platelet-rich plasma (PRP), adipose-derived stem cells (ASCs), and stromal vascular fraction (SVF) are related to increased survival of grafted adipose tissue. This study was the first simultaneous comparison of graft survival in combination with PRP, ASCs, and SVF. Adipose tissues were mixed with each other, injected subcutaneously into the back o...

  8. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis

    Rodriguez Jorge

    2009-04-01

    Full Text Available Abstract The stromal vascular fraction (SVF of adipose tissue is known to contain mesenchymal stem cells (MSC, T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.

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

    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.

  10. Adipose-Derived Stromal Vascular Fraction Cell Effects on a Rodent Model of Thin Endometrium.

    Robert K Hunter

    Full Text Available Endometrial dysfunction affects approximately 1% of infertile women, and there is currently no standard therapy for improving fertility treatment outcomes in these patients. In our study, we utilized a rodent model of thin endometrium to test whether intrauterine application of adipose-derived stromal vascular fraction cells (SVF could improve morphological and physiological markers of endometrial receptivity. Using anhydrous ethanol, endometrial area and gland density were significantly reduced in our model of thin endometrium. Application of SVF was associated with a 29% reduction in endometrial vascular endothelial growth factor (VEGF expression and significant increases in uterine artery systolic/diastolic velocity ratios and resistance index values, suggesting reduced diastolic microvascular tone. However, no significant improvements in endometrial area or gland density were observed following SVF treatment. 3D confocal imaging demonstrated poor engraftment of SVF cells into recipient tissue, which likely contributed to the negative results of this study. We suspect modified treatment protocols utilizing adjuvant estrogen and/or tail vein cell delivery may improve SVF retention and therapeutic response in subsequent studies. SVF is an easily-obtainable cell product with regenerative capability that may have a future role in the treatment of infertile women with endometrial dysfunction.

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

    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.

  12. Changes in adipose tissue stromal-vascular cells in primary culture due to porcine sera

    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 cm2 flasks, collagen-coated coverslips or petri dishes. Cell proliferation was measured by [3H]-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

  13. Development of a System and Method for Automated Isolation of Stromal Vascular Fraction from Adipose Tissue Lipoaspirate

    Swathi SundarRaj

    2015-01-01

    Full Text Available Autologous fat grafting for soft tissue reconstruction is challenged by unpredictable long-term graft survival. Fat derived stromal vascular fraction (SVF is gaining popularity in tissue reconstruction as SVF-enriched fat grafts demonstrate improved engraftment. SVF also has potential in regenerative medicine for remodeling of ischemic tissues by promoting angiogenesis. Since SVF cells do not require culture expansion, attempts are being made to develop automated devices to isolate SVF at the point of care. We report development of a closed, automated system to process up to 500 mL lipoaspirate using cell size-dependent filtration technology. The yield of SVF obtained by automated tissue digestion and filtration (1.17 ± 0.5 × 105 cells/gram was equivalent to that obtained by manual isolation (1.15 ± 0.3 × 105; p = 0.8, and the viability of the cells isolated by both methods was greater than 90%. Cell composition included CD34+CD31− adipose stromal cells, CD34+CD31+ endothelial progenitor cells, and CD34−CD31+ endothelial cells, and their relative percentages were equivalent to SVF isolated by the manual method. CFU-F capacity and expression of angiogenic factors were also comparable with the manual method, establishing proof-of-concept for fully automated SVF isolation, suitable for use in reconstructive surgeries and regenerative medicine applications.

  14. Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

    Camila Marx

    2014-01-01

    Full Text Available Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n=4 or allogeneic cultured adipose-derived stem cells (ASCs, n=5 injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases.

  15. Acupoint injection of autologous stromal vascular fraction and allogeneic adipose-derived stem cells to treat hip dysplasia in dogs.

    Marx, Camila; Silveira, Maiele Dornelles; Selbach, Isabel; da Silva, Ariel Silveira; Braga, Luisa Maria Gomes de Macedo; Camassola, Melissa; Nardi, Nance Beyer

    2014-01-01

    Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n = 4) or allogeneic cultured adipose-derived stem cells (ASCs, n = 5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases. PMID:25180040

  16. Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue

    AM Müller

    2010-03-01

    Full Text Available Grafts generated by cultivation of progenitor cells from the stromal vascular fraction of human adipose tissue have been proven to have osteogenic and vasculogenic properties in vivo. However, in vitro manufacture of such implants is challenged by complex, impractical and expensive processes, and requires implantation in a separate surgery. This study investigates the feasibility of an intraoperative approach to engineer cell-based bone grafts with tissue harvest, cell isolation, cell seeding onto a scaffold and subsequent implantation within a few hours. Freshly isolated adipose tissue cells from a total of 11 donors, containing variable fractions of mesenchymal and endothelial progenitors, were embedded at different densities in a fibrin hydrogel, which was wrapped around bone substitute materials based on beta-tricalcium phosphate (ChronOS®, hydroxyapatite (Engipore®, or acellular xenograft (Bio-Oss®. The resulting constructs, generated within 3 hours from biopsy harvest, were immediately implanted ectopically in nude mice and analysed after eight weeks. All explants contained blood vessels formed by human endothelial cells, functionally connected to the recipient’s vasculature. Human origin cells were also found within osteoid structures, positively immunostained for bone sialoprotein and osteocalcin. However, even with the highest loaded cell densities, no frank bone tissue was detected, independently of the material used. These results provide a proof-of-principle that an intraoperative engineering of autologous cell-based vasculogenic bone substitutes is feasible, but highlight that – in the absence of in vitro commitment – additional cues (e.g., low dose of osteogenic factors or orthotopic environmental conditions are likely needed to support complete osteoblastic cell differentiation and bone tissue generation.

  17. Regulation of adipogenesis by paracrine factors from adipose stromal-vascular fraction - a link to fat depot-specific differences.

    Meissburger, Bettina; Perdikari, Aliki; Moest, Hansjörg; Müller, Sebastian; Geiger, Matthias; Wolfrum, Christian

    2016-09-01

    Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to the development of metabolic dysfunction. We show here that adipocyte differentiation in subcutaneous stromal-vascular fraction (SVF) is increased compared to visceral SVF, however this increased differentiation capacity seems not to be due to changes in the number of adipocyte precursor cells. Rather, we demonstrate that secreted heat-sensitive factors from the SVF can inhibit adipocyte differentiation and that this effect is higher in visceral than in subcutaneous SVF, suggesting that visceral SVF is a source of secreted factors that can inhibit adipocyte formation. In order to explore secreted proteins that potentially inhibit differentiation in visceral preadipocytes we analyzed the secretome of both SVFs which led to the identification of 113 secreted proteins with an overlap of 42%. Further expression analysis in both depots revealed 16 candidates that were subsequently analyzed in a differentiation screen using an adenoviral knockdown system. From this analysis we were able to identify two potential inhibitory candidates, namely decorin (Dcn) and Sparc-like 1 (Sparcl1). We could show that ablation of either candidate enhanced adipogenesis in visceral preadipocytes, while treatment of primary cultures with recombinant Sparcl1 and Dcn blocked adipogenesis in a dose dependent manner. In conclusion, our data suggests that the differences in adipogenesis between depots might be due to paracrine and autocrine feedback mechanisms which could in turn contribute to metabolic homeostasis. PMID:27317982

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

    Vinay

    2015-10-01

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

  19. Case Report: Industrial X-Ray Injury Treated With Non-Cultured Autologous Adipose-Derived Stromal Vascular Fraction (SVF).

    Iddins, C J; Cohen, S R; Goans, R E; Wanat, R; Jenkins, M; Christensen, D M; Dainiak, N

    2016-08-01

    Local cutaneous injuries induced by ionizing radiation (IR) are difficult to treat. Many have reported local injection of adipose-derived stromal vascular fraction (SVF), often with additional therapies, as an effective treatment of IR-induced injury even after other local therapies have failed. The authors report a case of a locally recurrent, IR-induced wound that was treated with autologous, non-cultured SVF without other concurrent therapy. A nondestructive testing technician was exposed to 130 kVp x rays to his non-dominant right thumb on 5 October 2011. The wound healed 4 mo after initial conservative therapy with oral/topical α-tocopherol, oral pentoxifylline, naproxen sodium, low-dose oral steroids, topical steroids, hyperbaric oxygen therapy (HBOT), oral antihistamines, and topical aloe vera. Remission lasted approximately 17 mo with one minor relapse in July 2012 after minimal trauma and subsequent healing. Aggressive wound breakdown during June 2013 required additional therapy with HBOT. An erythematous, annular papule developed over the following 12 mo (during which time the patient was not undergoing prescribed treatment). Electron paramagnetic resonance (EPR) done more than 2 mo after exposure to IR revealed dose estimates of 14 ± 3 Gy and 19 ± 6 Gy from two centers using different EPR techniques. The patient underwent debridement of the 0.5 cm papular area, followed by SVF injection into and around the wound bed and throughout the thumb without complication. Eleven months post SVF injection, the patient has been essentially asymptomatic with an intact integument. These results raise the possibility of prolonged benefit from SVF therapy without the use of cytokines. Since there is currently no consensus on the use of isolated SVF therapy in chronic, local IR-induced injury, assessment of this approach in an appropriately powered, controlled trial in experimental animals with local radiation injury appears to be indicated. PMID:27356054

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

    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....... Genes most prominently and significantly upregulated by both conditions were growth factors (IGF1, BMP6, PDGFD, FGF9), adhesion molecule CLSTN2, extracellular matrix-related proteins such as matricellular proteins SMOC2, SPON1 and ADAMTS12, and inhibitors of proliferation (JAG1). The most significantly...... downregulated genes included matrix metalloproteinases (MMP3, MMP1), and proliferation markers (CDKN3) and GREM2 (a BMP6 antagonist). CONCLUSION: The decisive factor for the observed change in ASC gene expression proves to be serum starvation rather than VEGF stimulation. Changes in expression of growth factors...

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

    Introduction: Noninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of 99mTc-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 99mTc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of 99mTc-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 H2DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1. Results: An encouraging labeling efficiency of 33% was observed with 99mTc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays. Conclusion: 99mTc-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 99mTc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy

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

    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

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

    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. PMID:27580105

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

    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

  5. 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.

    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. PMID:26989865

  6. Cell-Assisted Lipotransfer for Cosmetic Breast Augmentation: Supportive Use of Adipose-Derived Stem/Stromal Cells

    Yoshimura, Kotaro; Sato, Katsujiro; Aoi, Noriyuki; Kurita, Masakazu; Hirohi, Toshitsugu; Harii, Kiyonori

    2007-01-01

    Background Lipoinjection is a promising treatment but has some problems, such as unpredictability and a low rate of graft survival due to partial necrosis. Methods To overcome the problems with lipoinjection, the authors developed a novel strategy known as cell-assisted lipotransfer (CAL). In CAL, autologous adipose-derived stem (stromal) cells (ASCs) are used in combination with lipoinjection. A stromal vascular fraction (SVF) containing ASCs is freshly isolated from half of the aspirated fa...

  7. Adipose tissue and vascular inflammation in coronary artery disease

    Enrica; Golia; Giuseppe; Limongelli; Francesco; Natale; Fabio; Fimiani; Valeria; Maddaloni; Pina; Elvira; Russo; Lucia; Riegler; Renatomaria; Bianchi; Mario; Crisci; Gaetano; Di; Palma; Paolo; Golino; Maria; Giovanna; Russo; Raffaele; Calabrò; Paolo; Calabrò

    2014-01-01

    Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences.As a consequence of the expansion of fat depots,in obese subjects,adipose tissue cells develope a phenotypic modification,which turns into a change of the secretory output.Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling,vascular biology and,moreover,participate to the systemic inflammatory response,which characterizes obesity and metabolic syndrome.This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events.A great number of adipocytokines have been described recently,linking inflammatory mileu and vascular pathology.The understanding of these pathways is crucial not only from a pathophysiological point of view,but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets.The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.

  8. Engineering of vascularized adipose constructs.

    Wiggenhauser, Paul S; Müller, Daniel F; Melchels, Ferry P W; Egaña, José T; Storck, Katharina; Mayer, Helena; Leuthner, Peter; Skodacek, Daniel; Hopfner, Ursula; Machens, Hans G; Staudenmaier, Rainer; Schantz, Jan T

    2012-03-01

    Adipose tissue engineering offers a promising alternative to the current surgical techniques for the treatment of soft tissue defects. It is a challenge to find the appropriate scaffold that not only represents a suitable environment for cells but also allows fabrication of customized tissue constructs, particularly in breast surgery. We investigated two different scaffolds for their potential use in adipose tissue regeneration. Sponge-like polyurethane scaffolds were prepared by mold casting with methylal as foaming agent, whereas polycaprolactone scaffolds with highly regular stacked-fiber architecture were fabricated with fused deposition modeling. Both scaffold types were seeded with human adipose tissue-derived precursor cells, cultured and implanted in nude mice using a femoral arteriovenous flow-through vessel loop for angiogenesis. In vitro, cells attached to both scaffolds and differentiated into adipocytes. In vivo, angiogenesis and adipose tissue formation were observed throughout both constructs after 2 and 4 weeks, with angiogenesis being comparable in seeded and unseeded constructs. Fibrous tissue formation and adipogenesis were more pronounced on polyurethane foam scaffolds than on polycaprolactone prototyped scaffolds. In conclusion, both scaffold designs can be effectively used for adipose tissue engineering. PMID:21850493

  9. Adipose tissue-derived stromal cells express neuronal phenotypes

    杨立业; 刘相名; 孙兵; 惠国桢; 费俭; 郭礼和

    2004-01-01

    Background Adipose tissue-derived stromal cells (ADSCs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons.Methods Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE).Results Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies.Conclusions The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.

  10. Induced Differentiation of Adipose-derived Stromal Cells into Myoblasts

    吴桂珠; 郑秀; 江忠清; 王金华; 宋岩峰

    2010-01-01

    This study aimed to induce the differentiation of isolated and purified adipose-derived stromal cells(ADSCs) into myoblasts,which may provide a new strategy for tissue engineering in patients with stress urinary incontinence(SUI).ADSCs,isolated and cultured ex vivo,were identified by flow cytometry and induced to differentiate into myoblasts in the presence of an induction solution consisting of DMEM supplemented with 5-azacytidine(5-aza),5% FBS,and 5% horse serum.Cellular morphology was observed under an i...

  11. Isolation and differentiation of stromal vascular cells to beige/brite cells

    Aune, Ulrike Liisberg; Ruiz, Lauren; Kajimura, Shingo

    2013-01-01

    cold exposure or by PPARγ agonists, therefore, this cell type has potential as a therapeutic target for obesity treatment. Although most immortalized adipocyte lines cannot recapitulate the process of "browning" of white fat in culture, primary adipocytes isolated from stromal vascular fraction in...... subcutaneous white adipose tissue (WAT) provide a reliable cellular system to study the molecular control of beige/brite cell development. Here we describe a protocol for effective isolation of primary preadipocytes and for inducing differentiation to beige/brite cells in culture. The browning effect can be...

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

    Cavirani Sandro; Conti Virna; Del Bue Maurizio; Morini Giorgio; Franceschi Valentina; Capocefalo Antonio; Donofrio Gaetano; Grolli Stefano

    2010-01-01

    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 tran...

  13. Glucose and Inflammatory Cells Decrease Adiponectin in Epicardial Adipose Tissue Cells: Paracrine Consequences on Vascular Endothelium.

    Fernández-Trasancos, Ángel; Guerola-Segura, Raquel; Paradela-Dobarro, Beatriz; Álvarez, Ezequiel; García-Acuña, José María; Fernández, Ángel Luis; González-Juanatey, José Ramón; Eiras, Sonia

    2016-05-01

    Epicardial adipose tissue (EAT) is a source of energy for heart that expresses the insulin-sensitizer, anti-inflammatory and anti-atherogenic protein, adiponectin. But, in coronary artery disease, adiponectin production declines. Our objective was to determine its regulation by glucose and inflammation in stromal cells from EAT and subcutaneous adipose tissue (SAT) and its paracrine effect on endothelial cells. Stromal cells of EAT and SAT were obtained from patients who underwent cardiac surgery. Adipogenesis was induced at 117, 200, or 295 mg/dl glucose, with or without macrophage-conditioned medium (MCM). Expression of adiponectin, GLUT-4 and the insulin receptor was analyzed by real-time PCR. The paracrine effect of stromal cells was determined in co-cultures with endothelial cells, by exposing them to high glucose and/or MCM, and, additionally, to leukocyte-conditioned medium from patients with myocardial infarction. The endothelial response was determined by analyzing vascular adhesion molecule expression. Our results showed a U-shaped dose-response curve of glucose on adiponectin in EAT, but not in SAT stromal cells. Conversely, MCM reduced the adipogenesis-induced adiponectin expression of EAT stromal cells. The presence of EAT stromal increased the inflammatory molecules of endothelial cells. This deleterious effect was emphasized in the presence of inflammatory cell-conditioned medium from patients with myocardial infarction. Thus, high glucose and inflammatory cells reduced adipogenesis-induced adiponectin expression of EAT stromal cells, which induced an inflammatory paracrine process in endothelial cells. This inflammatory effect was lower in presence of mature adipocytes, producers of adiponectin. These results contribute to understanding the role of EAT dysfunction on coronary atherosclerosis progression. PMID:26406271

  14. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment.

    Zhang, Tao; Tseng, Chieh; Zhang, Yan; Sirin, Olga; Corn, Paul G; Li-Ning-Tapia, Elsa M; Troncoso, Patricia; Davis, John; Pettaway, Curtis; Ward, John; Frazier, Marsha L; Logothetis, Christopher; Kolonin, Mikhail G

    2016-01-01

    White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression. PMID:27241286

  15. The cell-surface proteome of cultured adipose stromal cells.

    Donnenberg, Albert D; Meyer, E Michael; Rubin, J Peter; Donnenberg, Vera S

    2015-07-01

    In this technical note we describe a method to evaluate the cell surface proteome of human primary cell cultures and cell lines. The method utilizes the BD Biosciences lyoplate, a system covering 242 surface proteins, glycoproteins, and glycosphingolipids plus relevant isotype controls, automated plate-based flow cytometry, conventional file-level analysis and unsupervised K-means clustering of markers on the basis of percent of positive events and mean fluorescence intensity of positive and total clean events. As an example, we determined the cell surface proteome of cultured adipose stromal cells (ASC) derived from 5 independent clinical isolates. Between-sample agreement of very strongly expressed (n = 32) and strongly expressed (n =16) markers was excellent, constituting a reliable profile for ASC identification and determination of functional properties. Known mesenchymal markers (CD29, CD44, CD73, CD90, CD105) were among the identified strongly expressed determinants. Among other strongly expressed markers are several that are potentially immunomodulatory including three proteins that protect from complement mediated effects (CD46, CD55, and CD59), two that regulate apoptosis (CD77 and CD95) and several with ectoenzymatic (CD10, CD26, CD13, CD73, and CD143) or receptor tyrosine kinase (CD140b (PDGFR), CD340 (Her-2), EGFR) activity, suggesting mechanisms for the anti-inflammatory and tissue remodeling properties of ASC. Because variables are standardized for K-means clustering, results generated using this methodology should be comparable between instrumentation platforms. It is widely generalizable to human primary explant cultures and cells lines and will prove useful to determine how cell passage, culture interventions, and gene expression and silencing affect the cell-surface proteome. PMID:25929697

  16. Automated enumeration and viability measurement of canine stromal vascular fraction cells using fluorescence-based image cytometry method.

    Chan, Leo Li-Ying; Cohen, Donald A; Kuksin, Dmitry; Paradis, Benjamin D; Qiu, Jean

    2014-07-01

    In recent years, the lipoaspirate collected from adipose tissue has been seen as a valuable source of adipose-derived mesenchymal stem cells for autologous cellular therapy. For multiple applications, adipose-derived mesenchymal stem cells are isolated from the stromal vascular fraction (SVF) of adipose tissue. Because the fresh stromal vascular fraction typically contains a heterogeneous mixture of cells, determining cell concentration and viability is a crucial step in preparing fraction samples for downstream processing. Due to a large amount of cellular debris contained in the SVF sample, as well as counting irregularities standard manual counting can lead to inconsistent results. Advancements in imaging and optics technologies have significantly improved the image-based cytometric analysis method. In this work, we validated the use of fluorescence-based image cytometry for SVF concentration and viability measurement, by comparing to standard flow cytometry and manual hemocytometer. The concentration and viability of freshly collected canine SVF samples are analyzed, and the results highly correlated between all three methods, which validated the image cytometry method for canine SVF analysis, and potentially for SVF from other species. PMID:24740550

  17. A 3-month age difference profoundly alters the primary rat stromal vascular fraction phenotype.

    Quaade, Marlene Louise; Jensen, Charlotte Harken; Andersen, Ditte Caroline; Sheikh, Søren Paludan

    2016-06-01

    The stromal vascular fraction (SVF) is a heterogeneous population obtained from collagenase digestion of adipose tissue. When cultured the population becomes more homogeneous and the cells are then termed adipose stromal/stem cells (ASCs). Both the freshly isolated primary SVF population and the cultured ASC population possess regenerative abilities suggested to be mediated by paracrine mechanisms mainly. The use of ASCs and SVF cells, both in animal studies and human clinical studies, has dramatically increased during recent years. However, more knowledge regarding optimal donor characteristics such as age is demanded. Here we report that even a short age difference has an impact on the phenotype of primary SVF cells. We observed that a 3-month difference in relatively young adult rats affects the expression pattern of several mesenchymal stem cell markers in their primary SVF. The younger animals had significantly more CD90+/CD44+/CD29+/PDGFRα+primary cells, than the aged rats, suggesting an age dependent shift in the relative cell type distribution within the population. Taken together with recent studies of much more pronounced age differences, our data strongly suggest that donor age is a very critical parameter that should be taken into account in future stem cell studies, especially when using primary cells. PMID:27265810

  18. Human adipose-derived stromal cells in a clinically applicable injectable alginate hydrogel

    Larsen, Bjarke Follin; Juhl, Morten; Cohen, Smadar;

    2015-01-01

    BACKGROUND AIMS: Clinical trials have documented beneficial effects of mesenchymal stromal cells from bone marrow and adipose tissue (ASCs) as treatment in patients with ischemic heart disease. However, retention of transplanted cells is poor. One potential way to increase cell retention is to in...... and alginate is non-immunogenic and, in fact, immunosuppressive....

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

    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.

  20. "The preadipocyte factor" DLK1 marks adult mouse adipose tissue residing vascular cells that lack in vitro adipogenic differentiation potential

    Andersen, Ditte Caroline; Jensen, Line; Schrøder, Henrik Daa;

    2009-01-01

    Delta-like 1 (Dlk1) is expressed in 3T3-L1 preadipocytes and has frequently been referred to as "the" preadipocyte marker, yet the phenotype of DLK1(+) cells in adipose tissue remains undetermined. Herein, we demonstrate that DLK1(+) cells encompass around 1-2% of the adult mouse adipose stromal...... vascular fraction (SVF). Unexpectedly, the DLK1(+)SVF population was enriched for cells expressing genes generally ascribed to the vascular lineage and did not possess any adipogenic differentiation potential in vitro. Instead, DLK1(+) cells comprised an immediate ability for cobblestone formation......, generation of tube-like structures on matrigel, and uptake of Acetylated Low Density-Lipoprotein, all characteristics of endothelial cells. We therefore suggest that DLK1(+)SVF cells are of a vascular origin and not them-selves committed preadipocytes as assumed hitherto....

  1. Zfp423 promotes adipogenic differentiation of bovine stromal vascular cells.

    Yan Huang

    Full Text Available Intramuscular fat or marbling is critical for the palatability of beef. In mice, very recent studies show that adipocytes and fibroblasts share a common pool of progenitor cells, with Zinc finger protein 423 (Zfp423 as a key initiator of adipogenic differentiation. To evaluate the role of Zfp423 in intramuscular adipogenesis and marbling in beef cattle, we sampled beef muscle for separation of stromal vascular cells. These cells were immortalized with pCI neo-hEST2 and individual clones were selected by G418. A total of 288 clones (3×96 well plates were isolated and induced to adipogenesis. The presence of adipocytes was assessed by Oil-Red-O staining. Three clones with high and low adipogenic potential respectively were selected for further analyses. In addition, fibro/adipogenic progenitor cells were selected using a surface marker, platelet derived growth factor receptor (PDGFR α. The expression of Zfp423 was much higher (307.4±61.9%, P<0.05 in high adipogenic cells, while transforming growth factor (TGF-β was higher (156.1±48.7%, P<0.05 in low adipogenic cells. Following adipogenic differentiation, the expression of peroxisome proliferator-activated receptor γ (PPARγ and CCAAT/enhancer binding protein α (C/EBPα were much higher (239.4±84.1% and 310.7±138.4%, respectively, P<0.05 in high adipogenic cells. Over-expression of Zfp423 in stromal vascular cells and cloned low adipogenic cells dramatically increased their adipogenic differentiation, accompanied with the inhibition of TGF-β expression. Zfp423 knockdown by shRNA in high adipogenic cells largely prevented their adipogenic differentiation. The differential regulation of Zfp423 and TGF-β between low and high adipogenic cells is associated with the DNA methylation in their promoters. In conclusion, data show that Zfp423 is a critical regulator of adipogenesis in stromal vascular cells of bovine muscle, and Zfp423 may provide a molecular target for enhancing intramuscular

  2. Adipose Stromal Cells Contain Phenotypically Distinct Adipogenic Progenitors Derived from Neural Crest

    Yoshihiro Sowa; Tetsuya Imura; Toshiaki Numajiri; Kosuke Takeda; Yo Mabuchi; Yumi Matsuzaki; Kenichi Nishino

    2013-01-01

    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 contain...

  3. Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

    Lin Xue

    2011-03-01

    Full Text Available Abstract Background The aims of this study were: (1 to show the feasibility of using adipose-derived stromal vascular fraction (SVF as an alternative to bone marrow mono nuclear cell (BM-MNC for cell transplantation into chronic ischemic myocardium; and (2 to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI against left ventricular (LV remodelling and cardiac dysfunction. Methods Four weeks after left anterior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12 had SVF cell transplantation (6 × 106 cells. BM-MNC group (n = 12 received BM-MNCs (6 × 106 and the control (n = 10 had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20. Results At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition. Conclusions Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.

  4. Human Allogeneic Bone Marrow and Adipose Tissue Derived Mesenchymal Stromal Cells Induce CD8+ Cytotoxic T Cell Reactivity

    Roemeling-van Rhijn, Marieke; Reinders, Marlies E.; Franquesa, Marcella; Engela, Anja U; Korevaar, Sander S; Roelofs, Helene; Genever, Paul G; IJzermans, Jan NM; Betjes, Michiel GH; Baan, Carla C; Weimar, Willem; Hoogduijn, Martin J.

    2013-01-01

    Introduction For clinical applications, Mesenchymal Stromal Cells (MSC) can be isolated from bone marrow and adipose tissue of autologous or allogeneic origin. Allogeneic cell usage has advantages but may harbor the risk of sensitization against foreign HLA. Therefore, we evaluated whether bone marrow and adipose tissue-derived MSC are capable of inducing HLA-specific alloreactivity. Methods MSC were isolated from healthy human Bone Marrow (BM-MSC) and adipose tissue (ASC) donors. Peripheral ...

  5. Ultrastructural study of mouse adipose-derived stromal cells induced towards osteogenic direction.

    Tsupykov, Oleg; Ustymenko, Alina; Kyryk, Vitaliy; Smozhanik, Ekaterina; Yatsenko, Kateryna; Butenko, Gennadii; Skibo, Galina

    2016-06-01

    We investigated the ultrastructural characteristics of mouse adipose-derived stem/stromal cells (ASCs) induced towards osteogenic lineage. ASCs were isolated from adipose tissue of FVB-Cg-Tg(GFPU)5Nagy/J mice and expanded in monolayer culture. Flow cytometry, histochemical staining, and electron microscopy techniques were used to characterize the ASCs with respect to their ability for osteogenic differentiation capacity. Immunophenotypically, ASCs were characterized by high expression of the CD44 and CD90 markers, while the relative content of cells expressing CD45, CD34 and CD117 markers was alkaline phosphatase production. Electron microscopy analysis revealed that undifferentiated ASCs had a rough endoplasmic reticulum with dilated cisterns and elongated mitochondria. At the end of the osteogenic differentiation, the ASCs transformed from their original fibroblast-like appearance to having a polygonal osteoblast-like morphology. Ultrastructurally, these cells were characterized by large euchromatic nucleus and numerous cytoplasm containing elongated mitochondria, a very prominent rough endoplasmic reticulum, Golgi apparatus and intermediate filament bundles. Extracellular matrix vesicles of variable size similar to the calcification nodules were observed among collagen fibrils. Our data provide the ultrastructural basis for further studies on the cellular mechanisms involved in osteogenic differentiation of mouse adipose-derived stem/stromal cells. Microsc. Res. Tech. 79:557-564, 2016. © 2016 Wiley Periodicals, Inc. PMID:27087359

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

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

    2014-01-01

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

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

    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

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

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

    2016-01-01

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. ...

  9. Altered protein secretions during interactions between adipose tissue- or bone marrow-derived stromal cells and inflammatory cells

    Hattori, Hidemi; Ishihara, Masayuki

    2015-01-01

    Introduction Paracrine effects can be exploited in cell-based therapies that secrete factors, such as chemokines and cytokines, and can recruit inflammatory cells to transplants. In this study, mouse adipose tissue-derived stromal cells (ASCs) and bone marrow-derived stromal cells (ST2 cells) were used to examine changes in paracrine interactions with inflammation cells. Methods Green fluorescent protein positive (GFP+) bone marrow cells (BMCs) were injected into an irradiated mouse via the f...

  10. Myogenic differentiation and reparative activity of stromal cells derived from pericardial adipose in comparison to subcutaneous origin

    Wang, Xiaoming; Zhang, Hui; Nie, Liangming; Xu, Linhai; Chen, Min; Ding, Zhaoping

    2014-01-01

    Introduction Adipose tissue-derived stromal cells (ADSCs) are abundant and easy to obtain, but the diversity of differentiation potential from different locations may vary with the developmental origin of their mesenchymal compartment. We therefore aim to compare the myogenic differentiation and reparative activity of ADSCs derived from the pericardial tissue to ADSCs of subcutaneous origin. Methods Pericardial and inguinal adipose tissues from Wistar rats were surgically obtained, and the st...

  11. Isolation of Human Adipose-Derived Stromal Cells Using Laser-Assisted Liposuction and Their Therapeutic Potential in Regenerative Medicine

    Chung, Michael T.; Zimmermann, Andrew S.; Paik, Kevin J.; Shane D Morrison; Hyun, Jeong S.; Lo, David D; McArdle, Adrian; Montoro, Daniel T.; Walmsley, Graham G.; Senarath-Yapa, Kshemendra; Sorkin, Michael; Rennert, Robert; Chen, Hsin-Han; Chung, Andrew S.; Vistnes, Dean

    2013-01-01

    This study examined the impact of laser-assisted liposuction on the quality and differentiation potential of adipose-derived stromal cells (ASCs). It was found that laser-assisted liposuction negatively impacts the biology of ASCs, and therefore cell harvest using suction-assisted liposuction is preferable for tissue-engineering purposes.

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

    Lindolfo da Silva Meirelles

    2016-03-01

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

  13. Characterization and Multilineage Differentiation of Domestic and Black-Footed Cat Mesenchymal Stromal/Stem Cells from Abdominal and Subcutaneous Adipose Tissue.

    Gómez, Martha C; Qin, Qian; Biancardi, Monica N; Galiguis, Jason; Dumas, Cherie; MacLean, Robert A; Wang, Guoshun; Pope, C Earle

    2015-10-01

    Transplantation of mesenchymal stem cells (MSCs) isolated from bone marrow or adipose tissue is emerging as a promising tool for cell replacement therapy and regenerative medicine in domestic and endangered animal species. Defining the differentiation capability of adipose-derived mesenchymal stromal/stem cells (AMSCs) collected from different depot sites of adipose tissue will be essential for developing strategies for cell replacement therapy. In the present study, we compared the biological characteristics of domestic cat AMSCs isolated from visceral fat of the abdominal cavity (AB) with AMSCs from subcutaneous (SQ) tissue, and the functional capability of domestic and black-footed cat (Felis nigripes) AMSCs to differentiate into other cell types. Our results showed that both domestic and black-footed cat adipose-derived stromal vascular fractions contained AMSCs. Both domestic cat AB- and SQ-AMSCs showed important clonogenic ability and the minimal MSC immunophenotype as defined by the International Society for Cellular Therapy in humans. However, domestic cat AB-AMSCs had higher percentages of cells positive for MSCs-associated cluster of differentiation (CD) markers CD90(+) and CD105(+) (92% and 80%, respectively) than those of SQ-AMSCs (77% and 58%, respectively). Although these results may suggest that AB-AMSCs may be more multipotent than SQ-AMSCs, both types of cells showed similar expression of pluripotent genes Oct-4 and Klf4, except for higher expression of Nanog than in AB-AMSCs, and equivalent in vitro multilineage differentiation. Under appropriate stimuli, the black-footed cat and both domestic cat AB- and SQ-AMSCs differentiated not only toward mesoderm cell lineages but also toward ectoderm cell lineage, such as neuron cell-like cells. Black-footed cat AMSCs had more capability to differentiate toward chondrocytes. These results suggest that the defined AMSC population (regardless of site of collection) could potentially be employed as a

  14. Enhanced angiogenic effect of adipose-derived stromal cell spheroid with low-level light therapy in hindlimb ischemia mice

    Park, In-Su; Ahn, Jin-Chul; Chung, Phil-Sang

    2014-02-01

    Adipose-derived stromal cells (ASCs) are attractive cell source for tissue engineering. However, one obstacle to this approach is that the transplanted ASC population can decline rapidly in the recipient tissue. The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on transplanted human ASCs (hASCs) spheroid in a hindlimb ischemia animal model. LLLT, hASCs spheroid and hASCs spheroid transplantation with LLLT (spheroid + LLLT) were applied to the ischemic hindlimbs in athymic mice. The survival, differentiation and secretion of vascular endothelial growth (VEGF) of spheroid ASCs were evaluated by immunohistochemistry. The spheroid + LLLT group enhanced the tissue regeneration, including angiogenesis, compared with other groups. The spheroid contributed tissue regeneration via differentiation and secretion of growth factors. In the spheroid + LLLT group, the survival of spheroid hASCs was increased by the decreased apoptosis of spheroid hASCs in the ischemic hindlimb. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASCs group and spheroid group. These data suggest that LLLT is an effective biostimulator of spheroid hASCs in tissue regeneration that enhances the survival of ASCs and stimulates the secretion of growth factors in the ischemic hindlimb.

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

    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. PMID:24529434

  16. Conditioned Media From Adipose-Derived Stromal Cells Accelerates Healing in 3-Dimensional Skin Cultures.

    Collawn, Sherry S; Mobley, James A; Banerjee, N Sanjib; Chow, Louise T

    2016-04-01

    Wound healing involves a number of factors that results in the production of a "closed" wound. Studies have shown, in animal models, acceleration of wound healing with the addition of adipose-derived stromal cells (ADSC). The cause for the positive effect which these cells have on wound healing has not been elucidated. We have previously shown that addition of ADSC to the dermal equivalent in 3-dimensional skin cultures accelerates reepithelialization. We now demonstrate that conditioned media (CM) from cultured ADSC produced a similar rate of healing. This result suggests that a feedback from the 3-dimensional epithelial cultures to ADSC was not necessary to effect the accelerated reepithelialization. Mass spectrometry of CM from ADSC and primary human fibroblasts revealed differences in secretomes, some of which might have roles in the accelerating wound healing. Thus, the use of CM has provided some preliminary information on a possible mode of action. PMID:26954733

  17. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia;

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow...... human skin (human adult skin stromal cells, (hASSCs) and human new-born skin stromal cells (hNSSCs)) grew readily in culture and the growth rate was highest in hNSSCs and lowest in hATSCs. Compared with phenotype of hBM-MSC, all cell populations were CD34(-), CD45(-), CD14(-), CD31(-), HLA-DR(-), CD13......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and...

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

    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.

  19. Adipose-Derived Stromal Cell Therapy Affects Lung Inflammation and Tracheal Responsiveness in Guinea Pig Model of COPD

    Feizpour, Azadeh; Boskabady, Mohammad Hossein; Ghorbani, Ahmad

    2014-01-01

    The effects of adipose derived stromal cells (ASCs) were evaluated on tracheal responsiveness and biochemical parameters in guinea pigs model of chronic obstructive pulmonary disease (COPD). Thirty six guinea pigs were divided into 6 groups including: Control, COPD, COPD+intratracheal delivery of PBS (COPD+ITPBS), COPD+intravenous delivery of PBS (COPD+IVPBS), COPD+intratracheal delivery of ASCs (COPD+ITASC) and COPD+intravenous injection of ASCs (COPD+IVASC). COPD was induced by exposing ani...

  20. Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Triple Negative Breast Cancer Xenografts

    Rowan, Brian G.; Gimble, Jeffrey M; Sheng, Mei; Anbalagan, Muralidharan; Jones, Ryan K.; Frazier, Trivia P.; Asher, Majdouline; Lacayo, Eduardo A.; Friedlander, Paul L; Kutner, Robert; Chiu, Ernest S.

    2014-01-01

    Background Fat grafting is used to restore breast defects after surgical resection of breast tumors. Supplementing fat grafts with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve the regenerative/restorative ability of the graft and retention. However, long term safety for ASC grafting in proximity of residual breast cancer cells is unknown. The objective of this study was to determine the impact of human ASCs derived from abdominal lipoaspirates of three donors, on a ...

  1. Adipose Inflammation Initiates Recruitment of Leukocytes to Mouse Femoral Artery: Role of Adipo-Vascular Axis in Chronic Inflammation

    Hagita, Sumihiko; Osaka, Mizuko; Shimokado, Kentaro; Yoshida, Masayuki

    2011-01-01

    Background Although inflammation within adipose tissues is known to play a role in metabolic syndrome, the causative connection between inflamed adipose tissue and atherosclerosis is not fully understood. In the present study, we examined the direct effects of adipose tissue on macro-vascular inflammation using intravital microscopic analysis of the femoral artery after adipose tissue transplantation. Methods and Results We obtained subcutaneous (SQ) and visceral (VIS) adipose tissues from C5...

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

    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.

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

    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. Compatibility of Chitosan-Gelatin Films with Adipose Tissue Derived Stromal Cells

    ZHANG Ling; GAO Yuan; KONG Lijun; GONG Yandao; ZHAO Nanming; ZHANG Xiufang

    2006-01-01

    Chitosan has been shown to be a promising material for various applications in tissue engineering. Recently, adipose tissue derived stromal cells (ADSCs) have been investigated as an alternative source of seed cells for tissue engineering. The compatibility of chitosan and chitosan-gelatin complexes with ADSCs is not known. In the present study, ADSCs were isolated and characterized by phenotype using fluorescence-activated cell sorting (FACS). The morphology, viability, and the ability of the ADSCs to differentiate on chitosan and chitosan-gelatin composite films with 60 wt.% gelatin were evaluated. Results show that the ADSCs are positive for CD29, CD44, and CD105, but negative for CD31, CD34, and CD45. ADSCs adhere and grow better on the composite films than on the chitosan films. The ability of ADSCs to differentiate into osteogenic and adipogenic lineage cells is not affected by their being cultured on chitosan-gelatin composite films. Therefore, chitosan-gelatin composite films are compatible with ADSCs and do not impair the ability of ADSCs to differentiate into osteogenic and adipogenic lineage cells.

  5. Ultrastructure of neuronal-like cells differentiated from adult adipose-derived stromal cells

    Changqing Ye; Xiaodong Yuan; Hui Liu; Yanan Cai; Ya Ou

    2010-01-01

    β-mercaptoethanol induces in vitro adult adipose-derived stromal cells (ADSCs) to differentiate into neurons. However, the ultrastructural features of the differentiated neuronal-like cells remain unknown. In the present study, inverted phase contrast microscopy was utilized to observe β-mercaptcethanol-induced differentiation of neuronal-like cells from human ADSCs, and immunocytochemistry and real-time polymerase chain reaction were employed to detect expression of a neural stem cells marker (nestin), a neuronal marker (neuron-specific enolase), and a glial marker (glial fibrillary acidic protein). In addition, ultrastructure of neuronal-like cells was observed by transmission election microscopy. Results revealed highest expression rate of nestin and neuron-specific enolase at 3 and 5 hours following induced differentiation; cells in the 5-hour induction group exhibited a neuronal-specific structure, i.e., Nissl bodies. However, when induction solution was replaced by complete culture medium after 8-hour induction, the differentiated cells reverted to the fibroblast-like morphology from day 1. These results demonstrate that β-mercaptoethanol-induced ADSCs induced differentiation into neural stem cells, followed by morphology of neuronal-like cells. However, this differentiation state was not stable.

  6. Transplantation of Adipose Derived Stromal Cells into the Developing Mouse Eye

    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

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

    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.

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

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

    Tobin, L; Simonsen, L; Galbo, H; Bülow, Jens

    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....... Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue.Results:ATBF increased similarly in both groups during the adrenaline...

  10. In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue

    Agnieszka Śmieszek

    2015-01-01

    Full Text Available Metformin is applied not only as antidiabetic drug, but also in the treatment of obesity or as antiaging drug. The first part of the research discussed the effect of metformin at concentrations of 1 mM, 5 mM, and 10 mM on the morphology, ultrastructure, and proliferation potential of mice adipose-derived multipotent mesenchymal stromal cells (ASCs in vitro. Additionally, we determined the influence of metformin on mice adipose tissue metabolism. This study has shown for the first time that metformin inhibits the proliferative potential of ASCs in vitro in a dose- and time-dependent manner. In addition, we have found a significant correlation between the activity of ASCs and osteopontin at the mRNA and protein level. Furthermore, we have demonstrated that 5 mM and 10 mM metformin have cytotoxic effect on ASCs, causing severe morphological, ultrastructural, and apoptotic changes. The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3. The metformin influenced also circulating levels of OPN, which is what was found with systemic and local action of metformin. The results are a valuable source of information regarding the in vitro effect of metformin on adipose-derived stem cells.

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

    Ingrid R. Cordeiro

    2015-09-01

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

  12. Scaffold pore size modulates in vitro osteogenesis of human adipose-derived stem/stromal cells

    Trabecular bone has an interconnected porous structure, which influences cellular responses, biochemical transport and mechanical strength. Appropriately mimicking this structural organization in biomaterial scaffolds can facilitate more robust bone tissue regeneration and integration by providing a native microenvironment to the cells. This study examined the effect of pore size on human adipose-derived stem/stromal cell (ASC) osteogenesis within poly(ε-caprolactone) (PCL) scaffolds. Scaffold pore size was controlled by porogen leaching of custom-made paraffin particles with three different size ranges: P200 (< 500 µm), P500 (500–1000 µm), and P1000 (1000–1500 µm). Scaffolds produced by leaching these particles exhibited highly interconnected pores and rough surface structures that were favorable for cell attachment and ingrowth. The osteogenic response of ASCs was evaluated following 3 weeks of in vitro culture using biochemical (ALP, Ca2+/DNA content), mechanical (compression test) and histological (H and E and von Kossa staining) analyses. It was observed that while the total number of cells was similar for all scaffolds, the cell distributions and osteogenic properties were affected by the scaffold pore size. ASCs were able to bridge smaller pores and grow uniformly within these scaffolds (P200) while they grew as a layer along the periphery of the largest pores (P1000). The cell-biomaterial interactions specific to the latter case led to enhanced osteogenic responses. The ALP activity and Ca2+ deposition were doubled in P1000 scaffolds as compared to P200 scaffolds. A significant difference was observed between the compressive strength of unseeded and seeded P1000 scaffolds. Therefore, we demonstrated that the use of scaffolds with pores that are in the range of 1 mm enhances in vitro ASC osteogenesis, which may improve their performance in engineered bone substitutes. (paper)

  13. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

    Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to

  14. Upregulation of Stromal cell derived factor-1? in Collagen Vascular Diseases - associated interstitial pneumonias (CVDs-IPs)

    Margaritopoulos, Giorgos A.; Antoniou, Katerina M.; Soufla, Giannoula; Karagiannis, Konstantinos; Proklou, Athanasia; Lasithiotaki, Ismini; Tzanakis, Nikolaos; Spandidos, Demetrios A.; Siafakas, Nikolaos M

    2010-01-01

    Abstract Objective We speculated that distinct angiogenic profiles are involved in idiopathic interstitial pneumonias (IIPs) in comparison with interstitial pneumonias associated with collagen vascular disease (CVD-IPs). This hypothesis was investigated by measuring the expression of a cardinal biologic axis, the vascular endothelial growth factor (VEGF) ?stromal derived growth factor [SDF-1?, transcripts 1 and 2 (TR1 and TR2)] and receptor, CXCR4 and the angiogenetic re...

  15. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    Ribeiro Ricardo; Monteiro Cátia; Cunha Virgínia; Oliveira Maria; Freitas Mariana; Fraga Avelino; Príncipe Paulo; Lobato Carlos; Lobo Francisco; Morais António; Silva Vítor; Sanches-Magalhães José; Oliveira Jorge; Pina Francisco; Mota-Pinto Anabela

    2012-01-01

    Abstract Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat samples of periprostatic (PP) ...

  16. Stromal vascular fraction combined with silicone rubber chamber improves sciatic nerve regeneration in diabetes

    Rahim Mohammadi; Negin Sanaei; Sima Ahsan; Masoume Masoumi-Verki; Fatemeh Khadir; Aram Mokarizadeh

    2015-01-01

    Purpose:To study the effects of transplantation of characterized uncultured stromal vascular fraction (SVF) on sciatic nerve regeneration.Methods:A 10-mm sciatic nerve defect was bridged using a silicone conduit filled with SVF.In control group,silicone conduit was filled with phosphate-buffered saline alone.In sham-operated group,the sciatic nerve was only exposed and manipulated.The regenerated nerve fibers were studied 8 and 12 weeks after surgery.Results:Behavioral and functional studies confirmed faster recovery of regenerated axons in SVF transplanted animals than in control group (p < 0.05).Gastrocnemius muscle mass in SVF transplanted animal was found to be significantly more than that in control group.Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in SVF transplanted animals than in control group.In immunohistochemistry,the location of reactions to S-100 in SVF transplanted animals was clearly more positive than that in control group.Conclusion:SVF transplantation combined with silicone conduit could be considered as a readily accessible source of stromal cells that improves functional recovery of sciatic nerve.It may have clinical implications for the surgical management of acute diabetic patients after facial nerve transection.

  17. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance

    Elias, Ivet; Franckhauser, Sylvie; Ferré, Tura; Vilà, Laia; Tafuro, Sabrina; Muñoz, Sergio; Roca, Carles; Ramos, David; Pujol, Anna; Riu, Efren; Ruberte, Jesús; Bosch, Fatima

    2012-01-01

    During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adip...

  18. Multifunctional nanocrystalline calcium phosphates loaded with Tetracycline antibiotic combined with human adipose derived mesenchymal stromal stem cells (hASCs).

    Marycz, K; Pazik, R; Zawisza, K; Wiglusz, K; Maredziak, M; Sobierajska, P; Wiglusz, R J

    2016-12-01

    Osteoconductive drug delivery system composed of nanocrystalline calcium phosphates (Ca10(PO4)6(OH)2/β-Ca3(PO4)2) co-doped with Yb(3+)/Er(3+) ions loaded with Tetracycline antibiotic (TC) was developed. Their effect on human adipose derived mesenchymal stromal stem cells (hASCs) as a potential reconstructive biomaterial for bone tissue regeneration was studied. The XRD and TEM measurements were used in order to determine the crystal structure and morphology of the final products. The characteristics of nanocomposites with the TC and hASCs as potential regenerative materials as well as the antimicrobial activity of the nanoparticles against: Staphylococcus aureus ATCC 25923 as a model of the Gram-positive bacteria, Escherichia coli ATCC 8739 of the Gram-negative bacteria, were shown. These combinations can be a promising material for theranostic due to its regenerative, antimicrobial and fluorescent properties. PMID:27612684

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

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

  20. Role of adipose-derived stromal cells in pedicle skin flap survival in experimental animal models.

    Foroglou, Pericles; Karathanasis, Vasileios; Demiri, Efterpi; Koliakos, George; Papadakis, Marios

    2016-03-26

    The use of skin flaps in reconstructive surgery is the first-line surgical treatment for the reconstruction of skin defects and is essentially considered the starting point of plastic surgery. Despite their excellent usability, their application includes general surgical risks or possible complications, the primary and most common is necrosis of the flap. To improve flap survival, researchers have used different methods, including the use of adipose-derived stem cells, with significant positive results. In our research we will report the use of adipose-derived stem cells in pedicle skin flap survival based on current literature on various experimental models in animals. PMID:27022440

  1. Undifferentiated Human Adipose-derived Stromal/Stem Cells loaded onto Wet-Spun Starch-polycaprolactone Scaffolds Enhance Bone Regeneration: Nude Mice Calvarial Defect in vivo Study

    Carvalho, Pedro P.; Leonor, Isabel B.; Smith, Brenda J.; Dias, Isabel R.; Reis, Rui L.; Jeffrey M Gimble; Gomes, Manuela E.

    2013-01-01

    The repair of large bony defects remains challenging in the clinical setting. Human adipose-derived stromal/stem cells (hASCs) have been reported to differentiate along different cell lineages, including the osteogenic. The objective of the present study was to assess the bone regeneration potential of undifferentiated hASCs loaded in starch-polycaprolactone (SPCL) scaffolds, in a critical-sized nude mice calvarial defect.

  2. D609 induces vascular endothelial cells and marrow stromal cells differentiation into neuron-like cells

    Nan WANG; Chun-qing DU; Shao-shan WANG; Kun XIE; Shang-li ZHANG; Jun-ying MIAO

    2004-01-01

    AIM: To investigate the effect of tricyclodecane-9-yl-xanthogenate (D609) on cell differentiation in vascular endothelial cells (VECs) and marrow stromal cells (MSCs). METHODS: Morphological changes were observed under phase contrast microscope. Electron microscope and immunostaining were used for VECs identification. The expressions of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. RESULTS: After 6 h of induction with D609, some VECs showed morphological changes characteristic of neurones. 9 h later, more VECs became neuron-like cells. About 30.8 % of VECs displayed positive NSE (P<0.01), while the expression of GFAP was negative. When MSCs were exposed to D609, the cells displayed neuronal morphologies, such as pyramidal cell bodies and processes formed extensive networks at 3 h. 6 h later, almost all of the cells exhibited a typical neuronal appearance, and 85.6 % of MSCs displayed intensive positive NSE, but GFAP did not express. CONCLUSION: D609 induces VECs and MSCs differentiation into neuron-like cells.

  3. [Dynamics of osteogenesis associated with inoculation of autologous stromal cells from rat adipose tissue (experimental-morphological study)].

    Grigoryan, A S; Orlov, A A; Saburina, I N; Zurina, I M; Sysoev, S D

    2015-01-01

    Experiment was evaluated on 40 male Wistar rats. On the experimental model of mandible injury, bone autologous graft from tibia was placed on the surface of mandible (host bone). In the main experimental group, consisting of 20 animals, autologous rat adipose-derived stromal cells (ADSCs) were inoculated in space between autograph and host bones. ADSCs were not inoculated in the group of comparison. In experimental group with inoculated cells, the formation of a new fibroreticular bone structures in space between autograph and host bone was observed. These structures further underwent secondary reorganization and differentiation during the process of remodeling. As a result of the conducted study it was shown that in the experimental group by the day 180, statistically significant reduction of the area occupied by an immature fibroreticular bone took place. The reported phenomenon could be explained as a result of decline of the number of active cells in the population of inoculated ADSC, which is in consent with theory of limited cell division number due to telomeres shortening, described by Hayflick L. and Moorhead P.S. (1961). PMID:26571800

  4. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

  5. Tissue-Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose-Derived Stromal Cells In Vitro

    Polina I. Bobyleva

    2016-01-01

    Full Text Available Human adipose tissue-stromal derived cells (ASCs are considered a perspective tool for regenerative medicine. Depending on the application mode ASC/allogeneic immune cell interaction can occur in the systemic circulation under plenty high concentrations of O2 and in target tissues at lower O2 levels. Here we examined the effects of allogeneic PHA-stimulated peripheral blood mononuclear cells (PBMCs on ASCs under ambient (20% oxygen and “physiological” hypoxia (5% O2. As revealed with microarray analysis ASCs under 20% O2 were more affected by activated PBMCs, which was manifested in differential expression of more than 300 genes, whereas under 5% O2 only 140 genes were changed. Altered gene pattern was only partly overlapped at different O2 conditions. Under O2 ASCs retained their proliferative and differentiative capacities, mesenchymal phenotype, and intracellular organelle’ state. ASCs were proinflammatory activated on transcription level that was confirmed by their ability to suppress activation and proliferation of mitogen-stimulated PBMCs. ASC/PBMCs interaction resulted in anti-inflammatory shift of paracrine mediators in conditioning medium with significant increase of immunosuppressive LIF level. Our data indicated that under both ambient and tissue-related O2 ASCs possessed immunosuppressive potential and maintained functional activity. Under “physiological” hypoxia ASCs were less susceptible to “priming” by allogeneic mitogen-activated PBMCs.

  6. Tissue-Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose-Derived Stromal Cells In Vitro

    Bobyleva, Polina I.; Andreeva, Elena R.; Gornostaeva, Aleksandra N.; Buravkova, Ludmila B.

    2016-01-01

    Human adipose tissue-stromal derived cells (ASCs) are considered a perspective tool for regenerative medicine. Depending on the application mode ASC/allogeneic immune cell interaction can occur in the systemic circulation under plenty high concentrations of O2 and in target tissues at lower O2 levels. Here we examined the effects of allogeneic PHA-stimulated peripheral blood mononuclear cells (PBMCs) on ASCs under ambient (20%) oxygen and “physiological” hypoxia (5% O2). As revealed with microarray analysis ASCs under 20% O2 were more affected by activated PBMCs, which was manifested in differential expression of more than 300 genes, whereas under 5% O2 only 140 genes were changed. Altered gene pattern was only partly overlapped at different O2 conditions. Under O2 ASCs retained their proliferative and differentiative capacities, mesenchymal phenotype, and intracellular organelle' state. ASCs were proinflammatory activated on transcription level that was confirmed by their ability to suppress activation and proliferation of mitogen-stimulated PBMCs. ASC/PBMCs interaction resulted in anti-inflammatory shift of paracrine mediators in conditioning medium with significant increase of immunosuppressive LIF level. Our data indicated that under both ambient and tissue-related O2 ASCs possessed immunosuppressive potential and maintained functional activity. Under “physiological” hypoxia ASCs were less susceptible to “priming” by allogeneic mitogen-activated PBMCs. PMID:26880965

  7. Insights from a chimpanzee adipose stromal cell population: opportunities for adult stem cells to expand primate functional genomics.

    Pfefferle, Lisa W; Wray, Gregory A

    2013-01-01

    Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs with three comparable human cell lines. Consistent with previous studies on ASCs in humans, the chimpanzee cells have fibroblast-like morphology and express genes encoding components of the extracellular matrix at high levels. Differentially expressed genes are enriched for distinct functional classes between species: immunity and protein processing are higher in chimpanzees, whereas cell cycle and DNA processing are higher in humans. Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution. In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates. By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling. PMID:24092797

  8. Data on isolating mesenchymal stromal cells from human adipose tissue using a collagenase-free method

    Wassim Shebaby

    2016-03-01

    Full Text Available The present dataset describes a detailed protocol to isolate mesenchymal cells from human fat without the use of collagenase. Human fat specimen, surgically cleaned from non-fat tissues (e.g., blood vessels and reduced into smaller fat pieces of around 1–3 mm size, is incubated in complete culture media for five to seven days. Then, cells started to spread out from the fat explants and to grow in cultures according to an exponential pattern. Our data showed that primary mesenchymal cells presenting heterogeneous morphology start to acquire more homogenous fibroblastic-like shape when cultured for longer duration or when subcultured into new flasks. Cell isolation efficiency as well as cell doubling time were also calculated throughout the culturing experimentations and illustrated in a separate figure thereafter. This paper contains data previously considered as an alternative protocol to isolate adipose-derived mesenchymal stem cell published in “Proliferation and differentiation of human adipose-derived mesenchymal stem cells (ASCs into osteoblastic lineage are passage dependent” [1].

  9. Adipose-Derived Stem Cells for Future Regenerative System Medicine

    Yani Lina

    2012-08-01

    Full Text Available BACKGROUND: The potential use of stem cell-based therapies for repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of disease. Despite the advances, the availability of stem cells remaining a challenge for both scientist and clinicians in pursuing regenerative medicine. CONTENT: Subcutaneous human adipose tissue is an abundant and accessible cell source for applications in tissue engineering and regenerative medicine. Routinely, the adipose issue is digested with collagenase or related lytic enzymes to release a heterogeneous population for stromal vascular fraction (SVF cells. The SVF cells can be used directly or can be cultured in plastic ware for selection and expansion of an adherent population known as adipose-derived stromal/stem cells (ASCs. Their potential in the ability to differentiate into adipogenic, osteogenic, chondrogenic and other mesenchymal lineages, as well in their other clinically useful properties, includes stimulation of angiogenesis and suppression of inflammation. SUMMARY: Adipose tissue is now recognized as an accessible, abundant and reliable site for the isolation of adult stem cels suitable for the application of tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. KEYWORDS: adipose tissue, adult stem cells, regenerative medicine, mesenchymal stem cells.

  10. microRNA-145 Mediates the Inhibitory Effect of Adipose Tissue-Derived Stromal Cells on Prostate Cancer.

    Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Nakagawa, Takatoshi; Ibuki, Naokazu; Yoshikawa, Yuki; Tsujino, Takuya; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Minami, Koichiro; Uehara, Hirofumi; Komura, Kazumasa; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

    2016-09-01

    Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment. We also performed exosome microRNA (miRNA) array analysis to explore a mechanistic insight into the effect of ASCs on PCa cell proliferation/apoptosis. Both in vitro and in vivo experiments exhibited the inhibitory effect of ASCs on PC3M-luc2 cell proliferation, inducing apoptosis and PCa growth, respectively. Among upregulated miRNAs in ASCs compared with fibroblasts, we focused on miR-145, which was known as a tumor suppressor. ASC-derived conditioned medium (CM) significantly inhibited PC3M-luc2 cell proliferation, inducing apoptosis, but the effect was canceled by miR-145 knockdown in ASCs. ASC miR-145 knockdown CM also reduced the expression of Caspase 3/7 with increased antiapoptotic protein, BclxL, expression in PC3M-luc2 cells. This study provides preclinical data that ASCs inhibit PCa growth, inducing PCa cell apoptosis with reduced activity of BclxL, at least in part, by miR-145, including exosomes released from ASCs, suggesting that ASC administration could be a novel and promising therapeutic strategy in patients with PCa. PMID:27465939

  11. Effect of adipose-derived stromal cells and BMP12 on intrasynovial tendon repair: A biomechanical, biochemical, and proteomics study.

    Gelberman, Richard H; Shen, Hua; Kormpakis, Ioannis; Rothrauff, Benjamin; Yang, Guang; Tuan, Rocky S; Xia, Younan; Sakiyama-Elbert, Shelly; Silva, Matthew J; Thomopoulos, Stavros

    2016-04-01

    The outcomes of flexor tendon repair are highly variable. As recent efforts to improve healing have demonstrated promise for growth factor- and cell-based therapies, the objective of the current study was to enhance repair via application of autologous adipose derived stromal cells (ASCs) and the tenogenic growth factor bone morphogenetic protein (BMP) 12. Controlled delivery of cells and growth factor was achieved in a clinically relevant canine model using a nanofiber/fibrin-based scaffold. Control groups consisted of repair-only (no scaffold) and acellular scaffold. Repairs were evaluated after 28 days of healing using biomechanical, biochemical, and proteomics analyses. Range of motion was reduced in the groups that received scaffolds compared to normal. There was no effect of ASC + BMP12 treatment for range of motion or tensile properties outcomes versus repair-only. Biochemical assays demonstrated increased DNA, glycosaminoglycans, and crosslink concentration in all repair groups compared to normal, but no effect of ASC + BMP12. Total collagen was significantly decreased in the acellular scaffold group compared to normal and significantly increased in the ASC + BMP12 group compared to the acellular scaffold group. Proteomics analysis comparing healing tendons to uninjured tendons revealed significant increases in proteins associated with inflammation, stress response, and matrix degradation. Treatment with ASC + BMP12 amplified these unfavorable changes. In summary, the treatment approach used in this study induced a negative inflammatory reaction at the repair site leading to poor healing. Future approaches should consider cell and growth factor delivery methods that do not incite negative local reactions. PMID:26445383

  12. Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells

    Chiang Wen-Sheng

    2010-03-01

    Full Text Available Abstract Background Previous studies on the effects of aging in human and mouse mesenchymal stem cells suggest that a decline in the number and differentiation potential of stem cells may contribute to aging and aging-related diseases. In this report, we used stromal cells isolated from adipose tissue (ADSCs of young (8-10 weeks, adult (5 months, and old (21 months mice to test the hypothesis that mechanical loading modifies aging-related changes in the self-renewal and osteogenic and adipogenic differentiation potential of these cells. Results We show that aging significantly reduced the proliferation and increased the adipogenesis of ADSCs, while the osteogenic potential is not significantly reduced by aging. Mechanical loading (10% cyclic stretching, 0.5 Hz, 48 h increased the subsequent proliferation of ADSCs from mice of all ages. Although the number of osteogenic colonies with calcium deposition was increased in ADSCs subjected to pre-strain, it resulted from an increase in colony number rather than from an increase in osteogenic potential after strain. Pre-strain significantly reduced the number of oil droplets and the expression of adipogenic marker genes in adult and old ADSCs. Simultaneously subjecting ADSCs to mechanical loading and adipogenic induction resulted in a stronger inhibition of adipogenesis than that caused by pre-strain. The reduction of adipogenesis by mechanical strain was loading-magnitude dependent: loading with 2% strain only resulted in a partial inhibition, and loading with 0.5% strain could not inhibit adipogenesis in ADSCs. Conclusions We demonstrate that mechanical stretching counteracts the loss of self-renewal in aging ADSCs by enhancing their proliferation and, at the same time, reduces the heightened adipogenesis of old cells. These findings are important for the further study of stem cell control and treatment for a variety of aging related diseases.

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

    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.

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

    Dzobo, Kevin; Turnley, Taegyn; Wishart, Andrew; Rowe, Arielle; Kallmeyer, Karlien; van Vollenstee, Fiona A; Thomford, Nicholas E; Dandara, Collet; Chopera, Denis; Pepper, Michael S; Parker, M Iqbal

    2016-01-01

    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. PMID:27527147

  15. Quantification of stromal vascular cell mechanics with a linear cell monolayer rheometer

    Elkins, Claire M., E-mail: cma9@stanford.edu; Fuller, Gerald G. [Department of Chemical Engineering, Stanford University, Stanford, California 94305 (United States); Shen, Wen-Jun; Khor, Victor K.; Kraemer, Fredric B. [Division of Endocrinology, Gerontology and Metabolism, Stanford University, Stanford, California 94305 and Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304 (United States)

    2015-01-15

    Over the past few decades researchers have developed a variety of methods for measuring the mechanical properties of whole cells, including traction force microscopy, atomic force microscopy (AFM), and single-cell tensile testing. Though each of these techniques provides insight into cell mechanics, most also involve some nonideal conditions for acquiring live cell data, such as probing only one portion of a cell at a time, or placing the cell in a nonrepresentative geometry during testing. In the present work, we describe the development of a linear cell monolayer rheometer (LCMR) and its application to measure the mechanics of a live, confluent monolayer of stromal vascular cells. In the LCMR, a monolayer of cells is contacted on both top and bottom by two collagen-coated plates and allowed to adhere. The top plate then shears the monolayer by stepping forward to induce a predetermined step strain, while a force transducer attached to the top plate collects stress information. The stress and strain data are then used to determine the maximum relaxation modulus recorded after step-strain, G{sub r}{sup 0}, referred to as the zero-time relaxation modulus of the cell monolayer. The present study validates the ability of the LCMR to quantify cell mechanics by measuring the change in G{sub r}{sup 0} of a confluent cell monolayer upon the selective inhibition of three major cytoskeletal components (actin microfilaments, vimentin intermediate filaments, and microtubules). The LCMR results indicate that both actin- and vimentin-deficient cells had ∼50% lower G{sub r}{sup 0} values than wild-type, whereas tubulin deficiency resulted in ∼100% higher G{sub r}{sup 0} values. These findings constitute the first use of a cell monolayer rheometer to quantitatively distinguish the roles of different cytoskeletal elements in maintaining cell stiffness and structure. Significantly, they are consistent with results obtained using single-cell mechanical testing methods

  16. The impact of visceral adipose tissue and high-molecular weight adiponectin on cardio-ankle vascular index in asymptomatic Japanese subjects

    Ohashi, Norihiko; Ito, Chikako; Fujikawa, Rumi; Yamamoto, Hideya; Kihara, Yasuki; Kohno, Nobuoki

    2009-01-01

    Few studies addressed the relation of visceral adiposity and high-molecular weight (HMW) adiponectin to arterial stiffness. We investigated the impact of visceral adipose tissue (VAT) and HMW adiponectin on cardio-ankle vascular index (CAVI) in asymptomatic Japanese subjects. We studied 487 consecutive subjects (271 men and 216 women) who underwent general health examination between October 2005 and May 2008. The abdominal, visceral, and subcutaneous adipose tissue areas were determined by lo...

  17. Are They Really Stem Cells? Scrutinizing the Identity of Cells and the Quality of Reporting in the Use of Adipose Tissue-Derived Stem Cells

    Ernesto Balolong; Soojung Lee; Judee Grace Nemeno; Jeong Ik Lee

    2016-01-01

    There is an increasing concern that the term adipose tissue-derived stem cell (ASC) is inappropriately used to refer to the adipose stromal vascular fraction (SVF). To evaluate the accuracy and quality of reporting, 116 manuscripts on the application of ASC in humans and animals were examined based on the 2013 published International Federation for Adipose Therapeutics and Science (IFATS)/ International Society for Cellular Therapy (ISCT) joint statement and in reference to current guidelines...

  18. Construction of engineering adipose-like tissue in vivo utilizing human insulin gene-modified umbilical cord mesenchymal stromal cells with silk fibroin 3D scaffolds.

    Li, Shi-Long; Liu, Yi; Hui, Ling

    2015-12-01

    We evaluated the use of a combination of human insulin gene-modified umbilical cord mesenchymal stromal cells (hUMSCs) with silk fibroin 3D scaffolds for adipose tissue engineering. In this study hUMSCs were isolated and cultured. HUMSCs infected with Ade-insulin-EGFP were seeded in fibroin 3D scaffolds with uniform 50-60 µm pore size. Silk fibroin scaffolds with untransfected hUMSCs were used as control. They were cultured for 4 days in adipogenic medium and transplanted under the dorsal skins of female Wistar rats after the hUMSCs had been labelled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil). Macroscopical impression, fluorescence observation, histology and SEM were used for assessment after transplantation at 8 and 12 weeks. Macroscopically, newly formed adipose tissue was observed in the experimental group and control group after 8 and 12 weeks. Fluorescence observation supported that the formed adipose tissue originated from seeded hUMSCs rather than from possible infiltrating perivascular tissue. Oil red O staining of newly formed tissue showed that there was substantially more tissue regeneration in the experimental group than in the control group. SEM showed that experimental group cells had more fat-like cells, whose volume was larger than that of the control group, and degradation of the silk fibroin scaffold was greater under SEM observation. This study provides significant evidence that hUMSCs transfected by adenovirus vector have good compatibility with silk fibroin scaffold, and adenoviral transfection of the human insulin gene can be used for the construction of tissue-engineered adipose. PMID:23509085

  19. Adipose tissue stem cells meet preadipocyte commitment: going back to the future[S

    Cawthorn, William P; Erica L. Scheller; MacDougald, Ormond A.

    2012-01-01

    White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable of regeneration following surgical removal and massive expansion or contraction in response to altered energy balance. Research conducted for over 70 years has investigated adipose tissue plasticity on a cellular level, spurred on by the increasing burden that obesity and associated diseases are placing on public health globally. This work has identified committed preadipocytes in the stromal vascular fraction o...

  20. The New Role of CD163 in the Differentiation of Bone Marrow Stromal Cells into Vascular Endothelial-Like Cells

    Wei Lu

    2016-01-01

    Full Text Available Bone marrow stromal cells (BMSCs can differentiate into vascular endothelial cells (VECs. It is regarded as an important solution to cure many diseases, such as ischemic diseases and diabetes. However, the mechanisms underlying BMSC differentiation into VECs are not well understood. Recent reports showed that CD163 expression was associated with angiogenesis. In this study, overexpression of CD163 in BMSCs elevated the protein level of the endothelial-associated markers CD31, Flk-1, eNOS, and VE-cadherin, significantly increased the proportion of Alexa Fluor 488-acetylated-LDL-positive VECs, and promoted angiogenesis on Matrigel. Furthermore, we demonstrated that CD163 acted downstream homeobox containing 1 (Hmbox1 and upstream fibroblast growth factor 2 (FGF-2. These data suggested that CD163 was involved in Hmbox1/CD163/FGF-2 signal pathway in BMSC differentiation into vascular endothelial-like cells. We found a new signal pathway and a novel target for further investigating the gene control of BMSC differentiation into a VEC lineage.

  1. The New Role of CD163 in the Differentiation of Bone Marrow Stromal Cells into Vascular Endothelial-Like Cells.

    Lu, Wei; Su, Le; Yu, Zhezheng; Zhang, Shangli; Miao, Junying

    2016-01-01

    Bone marrow stromal cells (BMSCs) can differentiate into vascular endothelial cells (VECs). It is regarded as an important solution to cure many diseases, such as ischemic diseases and diabetes. However, the mechanisms underlying BMSC differentiation into VECs are not well understood. Recent reports showed that CD163 expression was associated with angiogenesis. In this study, overexpression of CD163 in BMSCs elevated the protein level of the endothelial-associated markers CD31, Flk-1, eNOS, and VE-cadherin, significantly increased the proportion of Alexa Fluor 488-acetylated-LDL-positive VECs, and promoted angiogenesis on Matrigel. Furthermore, we demonstrated that CD163 acted downstream homeobox containing 1 (Hmbox1) and upstream fibroblast growth factor 2 (FGF-2). These data suggested that CD163 was involved in Hmbox1/CD163/FGF-2 signal pathway in BMSC differentiation into vascular endothelial-like cells. We found a new signal pathway and a novel target for further investigating the gene control of BMSC differentiation into a VEC lineage. PMID:26880943

  2. Injectable cell/hydrogel microspheres induce the formation of fat lobule-like microtissues and vascularized adipose tissue regeneration

    In this paper, we demonstrated that collagen/alginate microspheres could be generated by a non-contact microfabrication device and serve as excellent cell embedding and delivery devices as they were porous, injectable and able to provide growth- and differentiation-supporting matrix for human adipose-derived stem cells (hASCs). The microsphere matrix demonstrated highly porous structure and mechanical stability for as long as 90 days. hASCs demonstrated high viability after microsphere formation as well as higher proliferation and more mature adipocytes induction compared to two-dimensional culture. After four weeks culture in adipogenic differentiation medium, adipocytes/collagen/alginate microspheres highly mimicking natural fat lobules were obtained and injected subcutaneously into the head of node mice. The in vivo study demonstrated vascularized adipose tissue formation in four weeks. The regenerated vasculature among the transplantation showed functional anastomosis with host vasculature, suggesting that these cell/hydrogel microspheres present injectable adipocytes delivery devices capable of generating vascularized adipose tissue in vivo and thus suitable for cell transplantation and tissue regeneration. (paper)

  3. Conjugated Linoleic Acid Induces Mast Cell Recruitment during Mouse Mammary Gland Stromal Remodeling12

    Russell, Joshua S.; McGee, Sibel Oflazoglu; Ip, Margot M.; Kuhlmann, Dietrich; Masso-Welch, Patricia A.

    2007-01-01

    Conjugated linoleic acid (CLA) is a dietary chemopreventive agent that induces apoptosis in the mammary adipose vascular endothelium and decreases mammary brown adipose tissue (BAT) and white adipose tissue (WAT). To determine onset and extent of stromal remodeling, we fed CD2F1/Cr mice diets supplemented with 1 or 2 g/100 g mixed CLA isomers for 1–7 wk. BAT loss, collagen deposition, and leukocyte recruitment occurred in the mouse mammary fat pad, coincident with an increase in parenchymal-a...

  4. 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

    Ithamar N. Stocchero

    2009-09-01

    Full Text Available Una de las situaciones más problemáticas para la vida íntima de una mujer, sobre todo si es joven, son las vulvo-vaginitis de repetición. Junto al herpes genital recidivante, suele ser causa de disarmonía en la relación de pareja por la situación en sí y por la frecuente presencia de dolor. Presentamos un caso exitoso en el que se aplicó un nuevo tratamiento consistente en la utilización de liponinjerto laminar submucoso, con preservación de la fracción vascular estromal (FVE, rica en células tronco derivadas de ese tejido (ADSCs, capaces de inducir neoangiogénesis que promoverá la defensa inmunológica normal de la mucosa de la vagina. De esta forma evitamos el uso de antibióticos y de otras terapias más costosas y, sobre todo, favoreciendo una vida sexual normal. Describimos en el presente artículo la técnica empleada.Uma das situações mais inconvenientes para a vida íntima de uma mulher, mormente jovem, é a vulvo-vaginite de repetição. Se acompanhada de herpes genital recidivante, não raro estabelece a desarmonia entre o casal dada à inconveniência da situação, além da dor, freqüentemente presente. Buscar o tratamento adequado, não prescrevendo apenas a antibióticoterapia, mas visando aumentar a resistência imunológica local da paciente, tem sido o objetivo de pesquisas nos últimos anos. Com o conhecimento da ação inflamatória induzida pelo tecido adiposo, associada à transferência de fatores vasculares estromais (FVE, grande fonte de células-tronco derivadas daquele tecido (ADSCs - Adipose- Derived Stromal/Stem Cells,bem como de indutores da angiogênese, facilitadora do acesso de células de defesa, foi idealizada uma nova e promissora linha de tratamento para estas pacientes: a lipoenxertia laminar. Relata-se a técnica bem sucedida, utilizada neste caso.One of the most inconvenient situations for a woman, mostly if young, is the recurrent vulvo-vaginitis. With the presence of a returning genital

  5. The effects of bone marrow mesenchymal stromal cells transplantation after mannitol pretreatment on behavioral performance and synaptophysin expression in the CA3 region in hippocampus of vascular dementia rats

    农伟东

    2013-01-01

    Objective To investigate the effects of bone marrow mesenchymal stromal cells (BMSCs) transplantation after mannitol pretreatment on behavioral performance and synaptophysin expression in the CA3region in hippocampus of vascular dementia (VD) rats.Methods The

  6. Human adipose stromal cells expanded in human serum promote engraftment of human peripheral blood hematopoietic stem cells in NOD/SCID mice

    Human mesenchymal stem cells (hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles, and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle, and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum (FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. In this study, we cultured human adipose stromal cells (hADSC) and bone marrow stroma cells (HBMSC) in human serum (HS) during their isolation and expansion, and demonstrated that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34(+) cells mobilized from bone marrow in NOD/SCID mice. Our results indicate that hADSC and hBMSC cultured in HS can be used for clinical trials of cell and gene therapies, including promotion of engraftment after allogeneic HSC transplantation

  7. In vitro and in vivo biocompatibility, bioavailability and tolerance of an injectable vehicle for adipose-derived stem/stromal cells for plastic surgery indications.

    Lequeux, Charlotte; Rodriguez, Jonathan; Boucher, Fabien; Rouyer, Ondine; Damour, Odile; Mojallal, Ali; Auxenfans, Céline

    2015-11-01

    Soft tissue reconstruction is a challenge in plastic surgery, when replacing lost materials and correcting contour defects. Many permanent and temporary fillers have been used to restore the volume of these lesions, but often with poor results and even complications. Adipose-derived stem/stromal cells (ASCs) and adipose tissue engineering have been suggested as valuable alternatives. In order to inject these cultured cells, it was essential to find a suitable vehicle. The purpose of this study was to evaluate Cytocare(®), an injectable medical device, composed of hyaluronic acid plus amino acids, vitamins and mineral salts. First, ASC viability and bioavailability in the 3 different available Cytocare(®) formulations using the MTT test were assessed; then an animal experiment, testing the tolerance after intradermal injections of both Cytocare(®) alone and with ASCs was carried out. Our in vitro results demonstrate a high biocompatibility of Cytocare(®) resulting in a better viability of ASCs when cultured in Cytocare(®) compared to culture medium (p < 0.05, Mann and Whitney). Cytocare(®) also permits their bioavailability and proliferation, making it a potential transfer vehicle that can retain the cells before their integration around the recipient site. Finally, our animal experiment shows that the ASC + Cytocare(®) combination is well tolerated. In conclusion, Cytocare(®) can be used as a biocompatible scaffold for cultured ASCs in therapeutic treatments, ensuring ASC bioavailability, as well as evidence of excellent tolerance in nude mice. PMID:26282247

  8. Implications of Pericardial, Visceral and Subcutaneous Adipose Tissue on Vascular Inflammation Measured Using 18FDG-PET/CT.

    Ho Cheol Hong

    Full Text Available Pericardial adipose tissue (PAT is associated with adverse cardiometabolic risk factors and cardiovascular disease (CVD. However, the relative implications of PAT, abdominal visceral and subcutaneous adipose tissue on vascular inflammation have not been explored.We compared the association of PAT, abdominal visceral fat area (VFA, and subcutaneous fat area (SFA with vascular inflammation, represented as the target-to-background ratio (TBR, the blood-normalized standardized uptake value measured using 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET in 93 men and women without diabetes or CVD. Age- and sex-adjusted correlation analysis showed that PAT, VFA, and SFA were positively associated with most cardiometabolic risk factors, including systolic blood pressure, LDL-cholesterol, triglycerides, glucose, insulin resistance and high sensitive C-reactive proteins (hsCRP, whereas they were negatively associated with HDL-cholesterol. In particular, the maximum TBR (maxTBR values were positively correlated with PAT and VFA (r = 0.48 and r = 0.45, respectively; both P <0.001, whereas SFA showed a relatively weak positive relationship with maxTBR level (r = 0.31, P = 0.003.This study demonstrated that both PAT and VFA are significantly and similarly associated with vascular inflammation and various cardiometabolic risk profiles.

  9. Adipose Tissue Biology: An Update Review

    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.

  10. A Comparative Translational Study: The Combined Use of Enhanced Stromal Vascular Fraction and Platelet-Rich Plasma Improves Fat Grafting Maintenance in Breast Reconstruction

    Gentile, Pietro; Orlandi, Augusto; Scioli, Maria Giovanna; Di Pasquali, Camilla; Bocchini, Ilaria; Curcio, Cristiano Beniamino; Floris, Micol; Fiaschetti, Valeria; Floris, Roberto; Cervelli, Valerio

    2012-01-01

    The use of autologous fat grafting is ideal in breast reconstruction. However, published data on long-term outcomes and instrumental results of fat grafting to the breast are lacking. The purpose of this study was to review the authors' experience of fat grafting, evaluating the effects related to the use of enhanced stromal vascular fraction (e-SVF) and fat grafting with platelet-rich plasma (PRP) in the maintenance of fat volume in breast reconstruction, comparing the results with a control...

  11. Long-term in-vivo tumorigenic assessment of human culture-expanded adipose stromal/stem cells

    MacIsaac, Zoe Marie, E-mail: zmm4a@virgina.edu [University of Virginia (United States); Shang, Hulan, E-mail: shanghulan@gmail.com [Department of Plastic Surgery, University of Virginia (United States); Agrawal, Hitesh, E-mail: hiteshdos@hotmail.com [Department of Plastic Surgery, University of Virginia (United States); Yang, Ning, E-mail: ny6u@virgina.edu [Department of Plastic Surgery, University of Virginia (United States); Parker, Anna, E-mail: amp4v@virginia.edu [Department of Surgery, University of Virginia (United States); Katz, Adam J., E-mail: ajk2f@virginia.edu [Department of Plastic Surgery, University of Virginia (United States)

    2012-02-15

    After more than a decade of extensive experimentation, the promise of stem cells to revolutionize the field of medicine has negotiated their entry into clinical trial. Adipose tissue specifically holds potential as an attainable and abundant source of stem cells. Currently undergoing investigation are adipose stem cell (ASC) therapies for diabetes and critical limb ischemia, among others. In the enthusiastic pursuit of regenerative therapies, however, questions remain regarding ASC persistence and migration, and, importantly, their safety and potential for neoplasia. To date, assays of in vivo ASC activity have been limited by early end points. We hypothesized that with time, ASCs injected subcutaneously undergo removal by normal tissue turnover and homeostasis, and by the host's immune system. In this study, a high dose of culture expanded ASCs was formulated and implanted as multicellular aggregates into immunocompromised mice, which were maintained for over one year. Animals were monitored for toxicity, and surviving cells quantified at study endpoint. No difference in growth/weight or lifespan was found between cell-treated and vehicle treated animals, and no malignancies were detected in treated animals. Moreover, real-time PCR for a human specific sequence, ERV-3, detected no persistent ASCs. With the advent of clinical application, clarification of currently enigmatic stem cell properties has become imperative. Our study represents the longest duration determination of stem cell activity in vivo, and contributes strong evidence in support of the safety of adipose derived stem cell applications. -- Highlights: Black-Right-Pointing-Pointer Adipose stem cells promise novel clinical therapies. Black-Right-Pointing-Pointer Before clinical translation, safety profiles must be further elucidated. Black-Right-Pointing-Pointer Subcutaneously injected non-autologous adipose stem cells do not form tumors. Black-Right-Pointing-Pointer Subcutaneously injected non

  12. Long-term in-vivo tumorigenic assessment of human culture-expanded adipose stromal/stem cells

    After more than a decade of extensive experimentation, the promise of stem cells to revolutionize the field of medicine has negotiated their entry into clinical trial. Adipose tissue specifically holds potential as an attainable and abundant source of stem cells. Currently undergoing investigation are adipose stem cell (ASC) therapies for diabetes and critical limb ischemia, among others. In the enthusiastic pursuit of regenerative therapies, however, questions remain regarding ASC persistence and migration, and, importantly, their safety and potential for neoplasia. To date, assays of in vivo ASC activity have been limited by early end points. We hypothesized that with time, ASCs injected subcutaneously undergo removal by normal tissue turnover and homeostasis, and by the host's immune system. In this study, a high dose of culture expanded ASCs was formulated and implanted as multicellular aggregates into immunocompromised mice, which were maintained for over one year. Animals were monitored for toxicity, and surviving cells quantified at study endpoint. No difference in growth/weight or lifespan was found between cell-treated and vehicle treated animals, and no malignancies were detected in treated animals. Moreover, real-time PCR for a human specific sequence, ERV-3, detected no persistent ASCs. With the advent of clinical application, clarification of currently enigmatic stem cell properties has become imperative. Our study represents the longest duration determination of stem cell activity in vivo, and contributes strong evidence in support of the safety of adipose derived stem cell applications. -- Highlights: ► Adipose stem cells promise novel clinical therapies. ► Before clinical translation, safety profiles must be further elucidated. ► Subcutaneously injected non-autologous adipose stem cells do not form tumors. ► Subcutaneously injected non-autologous adipose stem cells undergo complete removal by one year.

  13. Human Adipose-Derived Stromal/Stem Cells Induce Functional CD4+CD25+FoxP3+CD127− Regulatory T Cells Under Low Oxygen Culture Conditions

    Frazier, Trivia P.; McLachlan, James B.; Gimble, Jeffrey M.; Tucker, Hugh A; Brian G Rowan

    2014-01-01

    Human adipose tissue stromal/stem cells (ASCs) are known to induce proliferation of resting T cells under ambient (21%) O2 conditions; however, ASCs exist physiologically under lower oxygen (5% O2) conditions in adipose tissue. The effects of low oxygen levels on ASC immunomodulation of T cells are unknown. In this study, we show that ASCs stimulated proliferation of naive CD4+ T cells and the percentage of CD25+ T cells was significantly increased under both low and ambient O2. Forkhead box ...

  14. Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo.

    Mendez, Julio J; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum O; Steinbacher, Derek M; Leffell, David J; Niklason, Laura E

    2015-02-01

    Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608

  15. Reduction in Visceral Adiposity is Highly Related to Improvement in Vascular Endothelial Dysfunction among Obese Women: An Assessment of Endothelial Function by Radial Artery Pulse Wave Analysis

    Park, Si-Hoon; Shim, Kyung Won

    2005-01-01

    Because obesity is frequently complicated by other cardiovascular risk factors, the impact of a reduction in visceral adiposity on vascular endothelial dysfunction (VED) in obese patients is difficult to determine. In the present study, we evaluated the impact of a reduction in visceral adiposity on VED in obese women. Thirty-six premenopausal obese women (BMI ≥ 25 kg/m2) without complications were enrolled in the study. VED was evaluated by determining the augmentation index (AIx) from radia...

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

    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...

  17. Adipogenic Potential of Adipose Stem Cell Subpopulations

    Li, Han; Zimmerlin, Ludovic; Marra, Kacey G.; Donnenberg, Vera S.; Donnenberg, Albert D.; Rubin, J. Peter

    2014-01-01

    Background Adipose stem cells represent a heterogenous population. Understanding the functional characteristics of subpopulations will be useful in developing adipose stem cell–based therapies for regenerative medicine applications. The aim of this study was to define distinct populations within the stromal vascular fraction based on surface marker expression, and to evaluate the ability of each cell type to differentiate to mature adipocytes. Methods Subcutaneous whole adipose tissue was obtained by abdominoplasty from human patients. The stromal vascular fraction was separated and four cell populations were isolated by flow cytometry and studied. Candidate perivascular cells (pericytes) were defined as CD146+/CD31−/CD34−. Two CD31+ endothelial populations were detected and differentiated by CD34 expression. These were tentatively designated as mature endothelial (CD 31+/CD34−), and immature endothelial (CD31+/CD34+). Both endothelial populations were heterogeneous with respect to CD146. The CD31−/CD34+ fraction (preadipocyte candidate) was also CD90+ but lacked CD146 expression. Results Proliferation was greatest in the CD31−/CD34+ group and slowest in the CD146+ group. Expression of adipogenic genes, peroxisome proliferator-activated receptor-γ, and fatty acid binding protein 4, were significantly higher in the CD31−/CD34+ group compared with all other populations after in vitro adipogenic differentiation. This group also demonstrated the highest proportion of AdipoRed lipid staining. Conclusions The authors have isolated four distinct stromal populations from human adult adipose tissue and characterized their adipogenic potential. Of these four populations, the CD31/CD34+ group is the most prevalent and has the greatest potential for adipogenic differentiation. This cell type appears to hold the most promise for adipose tissue engineering. PMID:21572381

  18. Effects of In Vitro Low Oxygen Tension Preconditioning of Adipose Stromal Cells on Their In Vivo Chondrogenic Potential: Application in Cartilage Tissue Repair

    Gauthier, Olivier; Lesoeur, Julie; Sourice, Sophie; Masson, Martial; Fellah, Borhane Hakim; Geffroy, Olivier; Lallemand, Elodie; Weiss, Pierre

    2013-01-01

    Purpose Multipotent stromal cell (MSC)-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair. Methods MSC from rabbit or human adipose stromal cells (ASC) were preconditioned in vitro in control or chondrogenic (ITS and TGF-β) medium and in 21 or 5% O2. Chondrogenic commitment was monitored by measuring COL2A1 and ACAN expression (real-time PCR). Preconditioned rabbit and human ASC were then incorporated into an Si-HPMC hydrogel and injected (i) into rabbit articular cartilage defects for 18 weeks or (ii) subcutaneously into nude mice for five weeks. The newly formed tissue was qualitatively and quantitatively evaluated by cartilage-specific immunohistological staining and scoring. The phenotype of ASC cultured in a monolayer or within Si-HPMC in control or chondrogenic medium and in 21 or 5% O2 was finally evaluated using real-time PCR. Results/Conclusions 5% O2 increased the in vitro expression of chondrogenic markers in ASC cultured in induction medium. Cells implanted within Si-HPMC hydrogel and preconditioned in chondrogenic medium formed a cartilaginous tissue, regardless of the level of oxygen. In addition, the 3D in vitro culture of ASC within Si-HPMC hydrogel was found to reinforce the pro-chondrogenic effects of the induction medium and 5% O2. These data together indicate that although 5% O2 enhances the in vitro chondrogenic differentiation of ASC, it does not enhance their in vivo chondrogenesis. These results also highlight the in vivo chondrogenic potential of ASC and their potential value in cartilage repair. PMID:23638053

  19. Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO2 coating with magnesium impregnation

    The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO2) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (Sdr) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial–cell osteogenic interaction. - Highlights: • The magnesium loading presents a transitory effect on mesoporous TiO2 surface topography • The mesoporous structure promotes cellular attachment and spreading • The mesoporous structure activates osteogenesis of mesenchymal stem cells in absence of osteogenic promoters • The physical adsorbed magnesium is suggested to be involved in the expression of osteopontin

  20. Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO{sub 2} coating with magnesium impregnation

    Cecchinato, Francesca, E-mail: francesca.cecchinato@mah.se [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Karlsson, Johan [Department of Chemical and Biological Engineering, Applied Surface Chemistry, Chalmers University of Technology, Gothenburg (Sweden); Ferroni, Letizia; Gardin, Chiara [Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova (Italy); Galli, Silvia; Wennerberg, Ann [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Zavan, Barbara [Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova (Italy); Andersson, Martin [Department of Chemical and Biological Engineering, Applied Surface Chemistry, Chalmers University of Technology, Gothenburg (Sweden); Jimbo, Ryo [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki (Japan)

    2015-07-01

    The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO{sub 2}) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (S{sub dr}) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial–cell osteogenic interaction. - Highlights: • The magnesium loading presents a transitory effect on mesoporous TiO{sub 2} surface topography • The mesoporous structure promotes cellular attachment and spreading • The mesoporous structure activates osteogenesis of mesenchymal stem cells in absence of osteogenic promoters • The physical adsorbed magnesium is suggested to be involved in the expression of

  1. Preparation of bone marrow stromal cell antigen 2 targeted microbubbles and ultrasound molecular imaging for tumor vascular endothelial cells

    Objective: To prepare the bone marrow stromal cell antigen 2 (BST2)-targeted micro-bubbles (BST2-TMBs) for detecting the vascular endothelial cells of tumor via ultrasound molecular imaging technology. Methods: The targeted microbubbles (BST2-TMBs) were obtained through linking anti-BST2 antibodies to the surface of microbubbles via biotin-avidin bridge. The morphology of TMBs was examined under microscope and size distribution was observed using an optical particle counter. The specific binding of TMBs to endothelial cells was detected by in vitro cell adhesion assay. Murine prostatic carcinoma was used to investigate the capability of TMBs in detecting the vascular endothelial cells and for validating the expression of BST2 proteins. The t test was used by SPSS 19.0 to analyze the data. Results: The targeted microbubbles had the mean diameter of 1.61 μm, with 95% microbubbles between 1 to 5 μm. The in vitro cell adhesion assay demonstrated that the TMBs were able to specifically bind to the surface of endothelial cells, with (165 ±25) TMBs per field of view,significantly higher than that of the non-targeted microbubbles ((10 ± 3) microbubbles per field of view, t=10.662, P<0.01). The enhancement of ultrasonic signals of these cells bound with TMBs was also observed (TMBs: 27.93 ± 5.14 (gray-level), non-targeted microbubbles: 3.61 ± 1.67 (gray-level) ; t=7.239, P<0.01). Significant enhancement of signal intensity (gray-level: 38.79 ±0.29 at 7 min, remaining 47.65% of that (81.40 ±0.37) at 30 s) was found in the tumors of mice injected with BST2-TMBs, which was 4.27-fold higher than that (gray-level: 9.46 ±0.17 at 7 min, remaining 11.39% of that (83.01 ± 0.60) at 30 s) of mice injected with non-targeted microbubbles (t=65.587, P<0.01). This finding was further confirmed through immunohistochemistry assay. Conclusion: BST2-TMBs can be used for detecting the vascular endothelial cells of tumors via ultrasound molecular imaging. (authors)

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

    Highlights: ► We immortalized human adipose stromal cells (ASCs) with hTERT, Bmi-1, and SV40T. ► hTERT-only ASCs are prone to transformation, while Bmi-only ASCs become senescent. ► SV40T introduced along with hTERT abrogates proliferation control and multipotency. ► hTERT combined with Bmi-1 yields stable phenotype up to 140 population doublings. -- Abstract: Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASChTERT, ASCBmi-1, ASCBmi-1+hTERT and ASCSV40T+hTERT were tested for transgene expression, telomerase activity, surface immunomarkers, proliferation, osteogenic and adipogenic differentiation, karyotype, tumorigenicity, and cellular senescence. All cell lines have maintained expression of characteristic surface immunomarkers, and none was tumorigenic. However, ASCBmi-1 had limited replicative potential, while the rapidly proliferating ASCSV40T+hTERT acquired chromosomal aberrations, departed from MSC phenotype, and lost differentiation capacity. ASChTERT and ASChTERT+Bmi-1, on the other hand, preserved all essential MSC features and did not senesce after 100 population doublings. Notably, a subpopulation of ASChTERT also acquired aberrant karyotype and showed signs of transformation after long-term culture. In conclusion, hTERT alone was sufficient to extend the life span of human ASC, but ASChTERT are prone to transformation during extensive subculturing

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

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

    2012-05-25

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

  4. Insights from a Chimpanzee Adipose Stromal Cell Population: Opportunities for Adult Stem Cells to Expand Primate Functional Genomics

    Pfefferle, Lisa W.; Wray, Gregory A.

    2013-01-01

    Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose strom...

  5. RPL13A and EEF1A1 Are Suitable Reference Genes for qPCR during Adipocyte Differentiation of Vascular Stromal Cells from Patients with Different BMI and HOMA-IR

    Gentile, Adriana-Mariel; Lhamyani, Said; Coín-Aragüez, Leticia; Oliva-Olivera, Wilfredo; Zayed, Hatem; Vega-Rioja, Antonio; Monteseirin, Javier; Romero-Zerbo, Silvana-Yanina; Tinahones, Francisco-José; Bermúdez-Silva, Francisco-Javier; El Bekay, Rajaa

    2016-01-01

    Real-time or quantitative PCR (qPCR) is a useful technique that requires reliable reference genes for data normalization in gene expression analysis. Adipogenesis is among the biological processes suitable for this technique. The selection of adequate reference genes is essential for qPCR gene expression analysis of human Vascular Stromal Cells (hVSCs) during their differentiation into adipocytes. To the best of our knowledge, there are no studies validating reference genes for the analyses of visceral and subcutaneous adipose tissue hVSCs from subjects with different Body Mass Index (BMI) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. The present study was undertaken to analyze this question. We first analyzed the stability of expression of five potential reference genes: CYC, GAPDH, RPL13A, EEF1A1, and 18S ribosomal RNA, during in vitro adipogenic differentiation, in samples from these types of patients. The expression of RPL13A and EEF1A1 was not affected by differentiation, thus being these genes the most stable candidates, while CYC, GAPDH, and 18S were not suitable for this sort of analysis. This work highlights that RPL13A and EEF1A1 are good candidates as reference genes for qPCR analysis of hVSCs differentiation into adipocytes from subjects with different BMI and HOMA-IR. PMID:27304673

  6. Subcutaneous adipose tissue classification

    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

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

    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.

  8. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete 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 overnutrition 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. PMID:27148161

  9. Genome-wide analysis of gene expression during adipogenesis in human adipose-derived stromal cells reveals novel patterns of gene expression during adipocyte differentiation.

    Ambele, Melvin Anyasi; Dessels, Carla; Durandt, Chrisna; Pepper, Michael Sean

    2016-05-01

    We have undertaken an in-depth transcriptome analysis of adipogenesis in human adipose-derived stromal cells (ASCs) induced to differentiate into adipocytes in vitro. Gene expression was assessed on days 1, 7, 14 and 21 post-induction and genes differentially expressed numbered 128, 218, 253 and 240 respectively. Up-regulated genes were associated with blood vessel development, leukocyte migration, as well as tumor growth, invasion and metastasis. They also shared common pathways with certain obesity-related pathophysiological conditions. Down-regulated genes were enriched for immune response processes. KLF15, LMO3, FOXO1 and ZBTB16 transcription factors were up-regulated throughout the differentiation process. CEBPA, PPARG, ZNF117, MLXIPL, MMP3 and RORB were up-regulated only on days 14 and 21, which coincide with the maturation of adipocytes and could possibly serve as candidates for controlling fat accumulation and the size of mature adipocytes. In summary, we have identified genes that were up-regulated only on days 1 and 7 or days 14 and 21 that could serve as potential early and late-stage differentiation markers. PMID:27108396

  10. Flow cytometric characterization of culture expanded multipotent mesenchymal stromal cells (MSCs) from horse adipose tissue: towards the definition of minimal stemness criteria.

    Pascucci, L; Curina, G; Mercati, F; Marini, C; Dall'Aglio, C; Paternesi, B; Ceccarelli, P

    2011-12-15

    In the last decades, multipotent mesenchymal progenitor cells have been isolated from many adult tissues of different species. The International Society for Cellular Therapy (ISCT) has recently established that multipotent mesenchymal stromal cells (MSCs) is the currently recommended designation. In this study, we used flow cytometry to evaluate the expression of several molecules related to stemness (CD90, CD44, CD73 and STRO-1) in undifferentiated, early-passaged MSCs isolated from adipose tissue of four donor horses (AdMSCs). The four populations unanimously expressed high levels of CD90 and CD44. On the contrary, they were unexpectedly negative to CD73. A small percentage of the cells, finally, showed the expression of STRO-1. This last result might be due to the existence of a small subpopulation of STRO-1+ cells or to a poor cross-reactivity of the antibody. A remarkable donor-to-donor consistency and reproducibility of these findings was demonstrated. The data presented herein support the idea that equine AdMSCs may be easily isolated and selected by adherence to tissue culture plastic and exhibit a surface profile characterized by some peculiar differences in comparison to those described in other species. Continued characterization of these cells will help to clarify several aspects of their biology and may ultimately enable the isolation of specific, purified subpopulations. PMID:21839521

  11. Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells

    Yanez, Rosa, E-mail: rosamaria.yanez@ciemat.es; Oviedo, Alberto, E-mail: alberto.oviedo@ciemat.es; Aldea, Montserrat, E-mail: montserrat.aldea@ciemat.es; Bueren, Juan A., E-mail: juan.bueren@ciemat.es; Lamana, Maria L., E-mail: maruja.lamana@ciemat.es

    2010-11-15

    Mesenchymal stromal cells (MSCs) have important immunosuppressive properties, but the mechanisms and soluble factors involved in these effects remain unclear. We have studied prostaglandin-E2 (PGE2) as a possible candidate implied in adipose tissue-derived MSCs (Ad-MSCs) immunosuppressive properties over dendritic cells and T lymphocytes, compared to bone marrow derived MSCs (BM-MSCs). We found that both MSCs inhibited the maturation of myeloid-DCs and plasmocytoid-DCs. High levels of PGE2 were detected in DCs/MSCs co-cultures. Its blockade with indomethacin (IDM) allowed plasmocytoid-DCs but not myeloid-DCs maturation. Additionally, high levels of PGE2 were found in co-cultures in which Ad-MSCs or BM-MSCs inhibited activated T cells proliferation and pro-inflammatory cytokines production. PGE2 blockade by IDM preserved T lymphocytes proliferation but did not restore the pro-inflammatory cytokines secretion. However, an increased expression of transcription factors and cytokines genes involved in the Th1/Th2 differentiation pathway was detected in the T cells co-cultured with Ad-MSCs, but not with BM-MSCs. In conclusion, we propose that PGE2 is a soluble factor mediating most of the immunosuppressive effects of Ad-MSCs and BM-MSCs over p-DCs maturation and activated T lymphocytes proliferation and cytokine secretion.

  12. Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells

    Mesenchymal stromal cells (MSCs) have important immunosuppressive properties, but the mechanisms and soluble factors involved in these effects remain unclear. We have studied prostaglandin-E2 (PGE2) as a possible candidate implied in adipose tissue-derived MSCs (Ad-MSCs) immunosuppressive properties over dendritic cells and T lymphocytes, compared to bone marrow derived MSCs (BM-MSCs). We found that both MSCs inhibited the maturation of myeloid-DCs and plasmocytoid-DCs. High levels of PGE2 were detected in DCs/MSCs co-cultures. Its blockade with indomethacin (IDM) allowed plasmocytoid-DCs but not myeloid-DCs maturation. Additionally, high levels of PGE2 were found in co-cultures in which Ad-MSCs or BM-MSCs inhibited activated T cells proliferation and pro-inflammatory cytokines production. PGE2 blockade by IDM preserved T lymphocytes proliferation but did not restore the pro-inflammatory cytokines secretion. However, an increased expression of transcription factors and cytokines genes involved in the Th1/Th2 differentiation pathway was detected in the T cells co-cultured with Ad-MSCs, but not with BM-MSCs. In conclusion, we propose that PGE2 is a soluble factor mediating most of the immunosuppressive effects of Ad-MSCs and BM-MSCs over p-DCs maturation and activated T lymphocytes proliferation and cytokine secretion.

  13. Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells

    Maria Giuseppina Onesti

    2016-01-01

    Full Text Available Background. Systemic sclerosis (SSc is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia and opening (microstomia. We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS. Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO. In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials.

  14. Genome-wide analysis of gene expression during adipogenesis in human adipose-derived stromal cells reveals novel patterns of gene expression during adipocyte differentiation

    Melvin Anyasi Ambele

    2016-05-01

    Full Text Available We have undertaken an in-depth transcriptome analysis of adipogenesis in human adipose-derived stromal cells (ASCs induced to differentiate into adipocytes in vitro. Gene expression was assessed on days 1, 7, 14 and 21 post-induction and genes differentially expressed numbered 128, 218, 253 and 240 respectively. Up-regulated genes were associated with blood vessel development, leukocyte migration, as well as tumor growth, invasion and metastasis. They also shared common pathways with certain obesity-related pathophysiological conditions. Down-regulated genes were enriched for immune response processes. KLF15, LMO3, FOXO1 and ZBTB16 transcription factors were up-regulated throughout the differentiation process. CEBPA, PPARG, ZNF117, MLXIPL, MMP3 and RORB were up-regulated only on days 14 and 21, which coincide with the maturation of adipocytes and could possibly serve as candidates for controlling fat accumulation and the size of mature adipocytes. In summary, we have identified genes that were up-regulated only on days 1 and 7 or days 14 and 21 that could serve as potential early and late-stage differentiation markers.

  15. Effect of TiO2 nanoparticles on adipose derived stromal cell differentiation, morphology, ECM deposition and its susceptibility to bacterial infections

    Mironava, Tatsiana; Xu, Yan; Rafailovich, Miriam

    The growing annual production of Titanium dioxide (TiO2) nanoparticles is proportional to an increase in the chances of occupational and consumer exposure. Considering, that these nanoparticles are currently being used in multiple personal care products many concerns have arisen about their health impact. Human skin is in constant contact with the external environment and is one of the most important routes of exposure to TiO2. In this study we have investigated the effect of two forms of TiO2, rutile and anatase, on human adipose derived stromal cells (ADSCs). Here, we focus on the effects of TiO2 exposure on intracellular lipid accumulation and expression of adipogenic markers; on whether different forms of TiO2 have similar effects on cell function; and whether nanoparticle localization inside cells correlates with loss of cell function. In addition presence of bacteria on the skin is taken into account in its complex interaction with ADSCs and TiO2 nanoparticles. Altogether, the present study indicates that nanosized TiO2 particles adversely effects the differentiation of ADSCs, have profound effects on cell function and increase the rate of bacterial infection.

  16. Potential Biomedical Application of Enzymatically Treated Alginate/Chitosan Hydrosols in Sponges—Biocompatible Scaffolds Inducing Chondrogenic Differentiation of Human Adipose Derived Multipotent Stromal Cells

    Anna Zimoch-Korzycka

    2016-08-01

    Full Text Available Current regenerative strategies used for cartilage repair rely on biomaterial functionality as a scaffold for cells that may have potential in chondrogenic differentiation. The purpose of the research was to investigate the biocompatibility of enzymatically treated alginate/chitosan hydrosol sponges and their suitability to support chondrogenic differentiation of human adipose derived multipotent stromal cells (hASCs. The alginate/chitosan and enzyme/alginate/chitosan sponges were formed from hydrosols with various proportions and were used as a biomaterial in this study. Sponges were tested for porosity and wettability. The porosity of each sponge was higher than 80%. An equal dose of alginate and chitosan in the composition of sponges improved their swelling ability. It was found that equal concentrations of alginate and chitosan in hydrosols sponges assure high biocompatibility properties that may be further improved by enzymatic treatment. Importantly, the high biocompatibility of these biomaterials turned out to be crucial in the context of hydrosols’ pro-chondrogenic function. After exposure to the chondrogenic conditions, the hASCs in N/A/C and L/A/C sponges formed well developed nodules and revealed increased expression of collagen type II, aggrecan and decreased expression of collagen type I. Moreover, in these cultures, the reactive oxygen species level was lowered while superoxide dismutase activity increased. Based on the obtained results, we conclude that N/A/C and L/A/C sponges may have prospective application as hASCs carriers for cartilage repair.

  17. Targeting Artificial Tumor Stromal Targets for Molecular Imaging of Tumor Vascular Hypoxia.

    Nathan A Koonce

    Full Text Available Developed and tested for many years, a variety of tumor hypoxia detection methods have been inconsistent in their ability to predict treatment outcomes or monitor treatment efficacy, limiting their present prognostic capability. These variable results might stem from the fact that these approaches are based on inherently wide-ranging global tumor oxygenation levels based on uncertain influences of necrotic regions present in most solid tumors. Here, we have developed a novel non-invasive and specific method for tumor vessel hypoxia detection, as hypoxemia (vascular hypoxia has been implicated as a key driver of malignant progression, therapy resistance and metastasis. This method is based on high-frequency ultrasound imaging of α-pimonidazole targeted-microbubbles to the exogenously administered hypoxia marker pimonidazole. The degree of tumor vessel hypoxia was assessed in three mouse models of mammary gland carcinoma (4T1, SCK and MMTV-Wnt-1 and amassed up to 20% of the tumor vasculature. In the 4T1 mammary gland carcinoma model, the signal strength of α-pimonidazole targeted-microbubbles was on average 8-fold fold higher in tumors of pimonidazole-injected mice than in non-pimonidazole injected tumor bearing mice or non-targeted microbubbles in pimonidazole-injected tumor bearing mice. Overall, this provides proof of principle for generating and targeting artificial antigens able to be 'created' on-demand under tumor specific microenvironmental conditions, providing translational diagnostic, therapeutic and treatment planning potential in cancer and other hypoxia-associated diseases or conditions.

  18. Depressed Levels of Prostaglandin F2α in Mice Lacking Akr1b7 Increase Basal Adiposity and Predispose to Diet-Induced Obesity

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

    2012-01-01

    Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F2α (PGF2α) 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 PGF2α synthase activity. To test whether lack of Akr1b7 c...

  19. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues

    Honek, J.; Seki, T.; Iwamoto, H; Fischer, C.; Li, J.; Lim, S.; Samani, N. J.; Zang, J; Cao, Y.

    2014-01-01

    The etiology and mechanisms underlying the age-related high incidence of metabolic diseases such as type 2 diabetes are not fully understood. In this paper, we show that blood vasculatures in the adipose tissues experience continuous changes during aging and VEGF is a key angiogenic factor controlling microvessel numbers and functions. Surprisingly, targeting VEGF and VEGF receptor 2 by specific blocking drugs produces different and sometimes opposing effects on white adipocytes, resulting in...

  20. Development of a chemically defined serum-free medium for differentiation of rat adipose precursor cells

    Stromal-vascular cells from the epididymal fat pad of 4-week-old rats, when cultured in a medium containing insulin or insulin-like growth factor, IFG-I, triiodothyronine and transferrin, were able to undergo adipose conversion. Over ninety percent of the cells accumulated lipid droplets and this proportion was reduced in serum-supplemented medium. The adipose conversion was assessed by the development of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH) activities, [14]glucose incorporation into polar and neutral lipids, triacylglycerol accumulation and lipolysis in response to isoproterenol. Similar results were obtained with stromal-vascular cells from rat subcutaneous and retroperitoneal adipose tissues. Stromal-vascular cells required no adipogenic factors in addition to the components of the serum-free medium. Insulin was required within a physiological range of concentrations for the emergence of LPL and at higher concentrations for that of GPDH. When present at concentrations ranging from 2 to 50 nM, IGF-I was able to replace insulin for the expression of both LPL and and GPDH. The development of a serum free, chemically defined medium for the differentiation of diploid adiopose precursor cells opens up the possibility of characterizing inhibitors or activators of the adipose conversion process

  1. Development of a chemically defined serum-free medium for differentiation of rat adipose precursor cells

    Deslex, S.; Negrel, R.; Ailhaud, G.

    1987-01-01

    Stromal-vascular cells from the epididymal fat pad of 4-week-old rats, when cultured in a medium containing insulin or insulin-like growth factor, IFG-I, triiodothyronine and transferrin, were able to undergo adipose conversion. Over ninety percent of the cells accumulated lipid droplets and this proportion was reduced in serum-supplemented medium. The adipose conversion was assessed by the development of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH) activities, (/sup 14/)glucose incorporation into polar and neutral lipids, triacylglycerol accumulation and lipolysis in response to isoproterenol. Similar results were obtained with stromal-vascular cells from rat subcutaneous and retroperitoneal adipose tissues. Stromal-vascular cells required no adipogenic factors in addition to the components of the serum-free medium. Insulin was required within a physiological range of concentrations for the emergence of LPL and at higher concentrations for that of GPDH. When present at concentrations ranging from 2 to 50 nM, IGF-I was able to replace insulin for the expression of both LPL and and GPDH. The development of a serum free, chemically defined medium for the differentiation of diploid adiopose precursor cells opens up the possibility of characterizing inhibitors or activators of the adipose conversion process.

  2. The effect of low static magnetic field on osteogenic and adipogenic differentiation potential of human adipose stromal/stem cells

    Marędziak, Monika; Śmieszek, Agnieszka; Tomaszewski, Krzysztof A.; Lewandowski, Daniel; Marycz, Krzysztof

    2016-01-01

    The aim of this work was to investigate the effects of static magnetic field (SMF) on the osteogenic properties of human adipose derived mesenchymal stem cells (hASCs). In this study in seven days viability assay we examined the impact of SMF on cells proliferation rate, population doubling time, and ability to form single-cell derived colonies. We have also examined cells' morphology, ultrastructure and osteogenic properties on the protein as well as mRNA level. We established a complex approach, which enabled us to obtain information about SMF and hASCs potential in the context of differentiation into osteogenic and adipogenic lineages. We demonstrated that SMF enhances both viability and osteogenic properties of hASCs through higher proliferation factor and shorter population doubling time. We have also observed asymmetrically positioned nuclei and organelles after SMF exposition. With regards to osteogenic properties we observed increased levels of osteogenic markers i.e. osteopontin, osteocalcin and increased ability to form osteonodules with positive reaction to Alizarin Red dye. We have also shown that SMF besides enhancing osteogenic properties of hASCs, simultaneously decreases their ability to differentiate into adipogenic lineage. Our results clearly show a direct influence of SMF on the osteogenic potential of hASCs. These results provide key insights into the role of SMF on their cellular fate and properties.

  3. Identification of progesterone receptor in human subcutaneous adipose tissue.

    O'Brien, S N; Welter, B H; Mantzke, K A; Price, T M

    1998-02-01

    Sex steroids are postulated to play a role in adipose tissue regulation and distribution, because the amount and location of adipose tissue changes during puberty and menopause. Because of the nature of adipose tissue, receptors for the female sex steroids have been difficult to demonstrate. To date, estrogen receptor messenger RNA and protein have been identified in human subcutaneous adipose tissue, but the presence of progesterone receptor (PR) has not been reported. In this study, we demonstrate PR message by Northern blot analysis in RNA isolated from the abdominal subcutaneous adipose tissue of premenopausal women. These preliminary studies revealed that PR messenger RNA levels are higher in the stromal-vascular fraction as opposed to the adipocyte fraction. Western blot analysis demonstrates both PR protein isoforms (human PR-A and human PR-B) in human subcutaneous adipose tissue. Using an enzyme-linked immunosorbent assay, total PR could be quantitated. These studies substantiate that sex steroid receptors are present in human adipose tissue, thereby providing a direct route for regulation of adipose tissue by female sex steroids. PMID:9467566

  4. TGF-β1 and GDF5 Act Synergistically to Drive the Differentiation of Human Adipose Stromal Cells toward Nucleus Pulposus-like Cells.

    Colombier, Pauline; Clouet, Johann; Boyer, Cécile; Ruel, Maëva; Bonin, Gaëlle; Lesoeur, Julie; Moreau, Anne; Fellah, Borhane-Hakim; Weiss, Pierre; Lescaudron, Laurent; Camus, Anne; Guicheux, Jérôme

    2016-03-01

    Degenerative disc disease (DDD) primarily affects the central part of the intervertebral disc namely the nucleus pulposus (NP). DDD explains about 40% of low back pain and is characterized by massive cellular alterations that ultimately result in the disappearance of resident NP cells. Thus, repopulating the NP with regenerative cells is a promising therapeutic approach and remains a great challenge. The objectives of this study were to evaluate the potential of growth factor-driven protocols to commit human adipose stromal cells (hASCs) toward NP-like cell phenotype and the involvement of Smad proteins in this differentiation process. Here, we demonstrate that the transforming growth factor-β1 and the growth differentiation factor 5 synergistically drive the nucleopulpogenic differentiation process. The commitment of the hASCs was robust and highly specific as attested by the expression of NP-related genes characteristic of young healthy human NP cells. In addition, the engineered NP-like cells secreted an abundant aggrecan and type II collagen rich extracellular matrix comparable with that of native NP. Furthermore, we demonstrate that these in vitro engineered cells survived, maintained their specialized phenotype and secretory activity after in vivo transplantation in nude mice subcutis. Finally, we provide evidence suggesting that the Smad 2/3 pathway mainly governed the acquisition of the NP cell molecular identity while the Smad1/5/8 pathway controlled the NP cell morphology. This study offers valuable insights for the development of biologically-inspired treatments for DDD by generating adapted and exhaustively characterized autologous regenerative cells. Stem Cells 2016;34:653-667. PMID:26661057

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

    Debora B Mello

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

  6. Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes

    Du, Zhen-Yu; Ma, Tao; Lock, Erik-Jan;

    2011-01-01

    We have developed an in vitro hepatocyte-adipose tissue explant (ATE) co-culture model enabling examination of the effect of visceral and subcutaneous adipose tissues on primary rat hepatocytes. Initial analyses of inflammatory marker genes were performed in fractionated epididymal or inguinal ad......), particularly macrophages, in inguinal adipose tissue resulting in stronger responses in terms of hepatotoxicity and insulin-resistance....... elicited a stronger cytotoxic response and higher level of insulin resistance in the co-cultured hepatocytes. In conclusion, our results reveal depot-dependent effects of ATEs on co-cultured primary hepatocytes, which in part may be related to a more pronounced infiltration of stromal vascular cells (SVCs......We have developed an in vitro hepatocyte-adipose tissue explant (ATE) co-culture model enabling examination of the effect of visceral and subcutaneous adipose tissues on primary rat hepatocytes. Initial analyses of inflammatory marker genes were performed in fractionated epididymal or inguinal...

  7. In vitro differentiation of human adipose-derived adult stromal cells into neuron-like cells in hippocampal astrocyte conditioned medium

    Xinchun Ye; Hongjun He; Feng Yang; Kepeng Zhao; Jun Yao; Bin Liu

    2006-01-01

    BACKGROUND: At present, researches on differentiating from human adipose-derived adult stromal cells (hADASC) to neuron-like cells are focus on inducing by artificial-synthetic compound solution;however,hippocampal astrocyte conditioned medium(HCAM)can induce in vitro differentiation from hADASC to neuron-like cells is still unclear.OBJECTIVE:To observe whether HCAM can induce in vitro differentiation from hADASC to neuron-like cells.DESIGN:Randomized control study.SETTING:Department of Neurology,Taixing People's Hospital;Central Laboratory,North China Coal Medical College.MATERIALS:Donor of adipose tissue was donated by female volunteers suffering from caesarean section in the department of obstetrics & gynecology in our hospital and aged 20-35 years. Adipose tissue was collected from subcutaneous tissue of abdomen during the operation.In addition.8 male newborn Wistar rats within 24 hours with average body mass of 20 g were provided by Animal Institute of Chinese Academy of Medical Sciences.Rabbit-anti-human Nestin polyclonal antibody.Rabbit-anti-human glial fibriliary acidic protein (GFAP)polyclonal antibody, rabbit-anti-human neuro-specific enolase polyclonal antibody and mouse-anti-human microtubal associated protein 2(MAP-2)polyclonal antibody were provided by Wuhan Boster Company.METHODS:The experiment was carried out in the Central Laboratory of North China Coal Medical College from October 2004 to June 2005.hADASC was cultured with HCAM and its growth and morphological changes were observed under inverted phase contrast microscope.Immunocytochemistry.immunofluorescence and Western blotting were used to evaluate the expressions of Nestin,which was a specific sign of nerve precursor,neuro-specific enolase and MAP-2,which was a specific sign of nerve cell,and GFAP,which was a specific sign of neuroglial cells.MAIN OUTCOME MEASURES:Nestin,which was a specific sign of nerve precursor,neuro-specific enolase and MAP-2,which was a specific sign of nerve cell

  8. Prevalence of Endogenous CD34+ Adipose Stem Cells Predicts Human Fat Graft Retention in a Xenograft Model

    Philips, Brian J.; Grahovac, Tara L.; Valentin, Jolene E.; Chung, Christopher W.; Bliley, Jacqueline M.; Pfeifer, Melanie E.; Roy, Sohini B.; Dreifuss, Stephanie; Kelmendi-Doko, Arta; Kling, Russell E.; Ravuri, Sudheer K.; Marra, Kacey G.; Donnenberg, Vera S.; Donnenberg, Albert D.; Rubin, J. Peter

    2014-01-01

    Background Fat grafting is a promising technique for soft-tissue augmentation, although graft retention is highly unpredictable and factors that affect graft survival have not been well defined. Because of their capacity for differentiation and growth factor release, adipose-derived stem cells may have a key role in graft healing. The authors’ objective was to determine whether biological properties of adipose-derived stem cells present within human fat would correlate with in vivo outcomes of graft volume retention. Methods Lipoaspirate from eight human subjects was processed using a standardized centrifugation technique and then injected subcutaneously into the flanks of 6-week-old athymic nude mice. Graft masses and volumes were measured, and histologic evaluation, including CD31+ staining for vessels, was performed 8 weeks after transplantation. Stromal vascular fraction isolated at the time of harvest from each subject was analyzed for surface markers by multi-parameter flow cytometry, and also assessed for proliferation, differentiation capacity, and normoxic/hypoxic vascular endothelial growth factor secretion. Results Wide variation in percentage of CD34+ progenitors within the stromal vascular fraction was noted among subjects and averaged 21.3 ± 15 percent (mean ± SD). Proliferation rates and adipogenic potential among stromal vascular fraction cells demonstrated moderate interpatient variability. In mouse xenograft studies, retention volumes ranged from approximately 36 to 68 percent after 8 weeks, with an overall average of 52 ± 11 percent. A strong correlation (r = 0.78, slope = 0.76, p < 0.05) existed between stromal vascular fraction percentage of CD34+ progenitors and high graft retention. Conclusion Inherent biological differences in adipose tissue exist between patients. In particular, concentration of CD34+ progenitor cells within the stromal vascular fraction may be one of the factors used to predict human fat graft retention. (Plast

  9. Adipose Tissue Engineering - In vitro Development of a subcutaneous fat layer and a vascularized adipose tissue construct utilizing extracellular matrix structures

    Werner, Katharina Julia

    2014-01-01

    Each year millions of plastic and reconstructive procedures are performed to regenerate soft tissue defects after, for example, traumata, deep burns or tumor resections. Tissue engineered adipose tissue grafts are a promising alternative to autologous fat transfer or synthetic implants to meet this demand for adipose tissue. Strategies of tissue engineering, especially the use of cell carriers, provide an environment for better cell survival, an easier positioning and supplemented with the ap...

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

    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

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

    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

  12. Agent-based model of therapeutic adipose-derived stromal cell trafficking during ischemia predicts ability to roll on P-selectin.

    Alexander M Bailey

    2009-02-01

    Full Text Available Intravenous delivery of human adipose-derived stromal cells (hASCs is a promising option for the treatment of ischemia. After delivery, hASCs that reside and persist in the injured extravascular space have been shown to aid recovery of tissue perfusion and function, although low rates of incorporation currently limit the safety and efficacy of these therapies. We submit that a better understanding of the trafficking of therapeutic hASCs through the microcirculation is needed to address this and that selective control over their homing (organ- and injury-specific may be possible by targeting bottlenecks in the homing process. This process, however, is incredibly complex, which merited the use of computational techniques to speed the rate of discovery. We developed a multicell agent-based model (ABM of hASC trafficking during acute skeletal muscle ischemia, based on over 150 literature-based rules instituted in Netlogo and MatLab software programs. In silico, trafficking phenomena within cell populations emerged as a result of the dynamic interactions between adhesion molecule expression, chemokine secretion, integrin affinity states, hemodynamics and microvascular network architectures. As verification, the model reasonably reproduced key aspects of ischemia and trafficking behavior including increases in wall shear stress, upregulation of key cellular adhesion molecules expressed on injured endothelium, increased secretion of inflammatory chemokines and cytokines, quantified levels of monocyte extravasation in selectin knockouts, and circulating monocyte rolling distances. Successful ABM verification prompted us to conduct a series of systematic knockouts in silico aimed at identifying the most critical parameters mediating hASC trafficking. Simulations predicted the necessity of an unknown selectin-binding molecule to achieve hASC extravasation, in addition to any rolling behavior mediated by hASC surface expression of CD15s, CD34, CD62e, CD62p

  13. EET agonist prevents adiposity and vascular dysfunction in rats fed a high fat diet via a decrease in Bach 1 and an increase in HO-1 levels.

    Sodhi, Komal; Puri, Nitin; Inoue, Kazuyoshi; Falck, John R; Schwartzman, Michal L; Abraham, Nader G

    2012-08-01

    Recent reports have shown interplay between EETs (epoxides) and the heme oxygenase (HO) system in attenuating adipogenesis in cell culture models; prompting an examination of the effectiveness of EET agonist on obesity and associated cardio-metabolic dysfunction. Patho-physiological effects of an EET agonist (NUDSA) were contrasted in the absence and in the presence of stannous mesoporphyrin (an HO inhibitor) in SD rats fed a high fat (58%, HF) for 16 weeks. Animals on HF diet exhibited enhanced oxidative stress, increased levels of inflammatory cytokines and decreased levels of adiponectin along with reduced vascular and adipose tissue levels of EETs, HO-1; as compared to control rats (11% dietary fat). Treatment with NUDSA not only reversed serum adiponectin and vascular and adipose tissue levels of EETs and HO-1, but also, decreased blood pressure, subcutaneous and visceral fat content and serum TNFα and IL-6 levels in rats on HF diet. Aortic endothelial function, peNOS expression and adipose tissue markers of energy homeostasis i.e. pAMPK, Sirt1 and FAS, impaired in rats fed a HF diet, were restored in animals treated with this EET agonist. That NUDSA enhanced HO-1 expression, was accompanied by increase in p-GSK-3β and pAKT levels along with attenuation of adipose tissue levels of Bach 1--the transcriptional suppresser of HO-1 expression. Prevention of these beneficial effects of NUDSA, in animals on HF diet and concurrently exposed to NUDSA and SnMP, supports the role of EET-HO interaction in mediating such effects. Taken together, our findings suggest that the EETs stimulate HO-1 expression via suppression of Bach 1 and interplay of these two systems affords vascular and metabolic protection in diet induced obesity. PMID:22209722

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

    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

  15. Management of knee osteoarthritis by combined stromal vascular fraction cell therapy, platelet-rich plasma, and musculoskeletal exercises: a case series

    Gibbs N

    2015-11-01

    Full Text Available Nathan Gibbs,1 Rod Diamond,2 Eric O Sekyere,3 Wayne D Thomas4 1South Sydney Sports Medicine, Kensington, 2Diamond Health Care, Kensington, 3Endeavour College of Natural Health, Sydney, 4Cell-Innovations Pty Ltd, Liverpool, NSW, Australia Introduction: Knee osteoarthritis is associated with persistent joint pain, stiffness, joint deformities, ligament damage, and surrounding muscle atrophy. The complexity of the disease makes treatment difficult. There are no therapeutic drugs available to halt the disease progression, leaving patients dependent on pain medication, anti-inflammatory drugs, or invasive joint replacement surgery. Case presentations: Four patients with a history of unresolved symptomatic knee osteoarthritis were investigated for the therapeutic outcome of combining an exercise rehabilitation program with intra-articular injections of autologous StroMed (ie, stromal vascular fraction cells concentrated by ultrasonic cavitation from lipoaspirate and platelet-rich plasma (PRP. The Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS was administered along with physical function tests over a 12-month period. The first patient achieved a maximum therapeutic outcome of 100 in all five KOOS subscales (left knee, and 100 for four subscales (right knee. The second patient scored 100 in all five KOOS subscales (left knee, and greater than 84 in all subscales (right knee. Treatment of the third patient resulted in improved outcomes in both knees of >93 for four KOOS subscales, and 60 for the Function in Sport and Recreation subscale. The fourth patient improved to 100 in all five KOOS subscales. In all patients, the physical function “Get-up and Go” test and “Stair Climbing Test” returned to normal (a value of zero. Conclusion: This case series indicates that improved outcomes may be obtained when autologous stromal vascular fraction (StroMed cell therapy is combined with traditional exercise practices and PRP for

  16. Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

    Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

    2015-07-17

    Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

  17. Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

    Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

  18. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    Ribeiro Ricardo

    2012-04-01

    Full Text Available Abstract Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants or stromal vascular fraction (SVF from paired fat samples of periprostatic (PP and pre-peritoneal visceral (VIS anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs 2 and 9 activity. The effects of those conditioned media (CM on growth and migration of hormone-refractory (PC-3 and hormone-sensitive (LNCaP prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration

  19. 4-Hydroxynonenal Regulates TNF-α Gene Transcription Indirectly via ETS1 and microRNA-29b in Human Adipocytes Induced From Adipose Tissue-Derived Stromal Cells.

    Zhang, Xi-Mei; Guo, Lin; Huang, Xiang; Li, Qiu-Ming; Chi, Mei-Hua

    2016-08-01

    Obesity is characterized by an accumulation of excessive body fat and can be diagnosed by a variety of measures, such as BMI. However, in some obese individuals, oxidative stress is also thought to be an important pathogenic mechanism of obesity-associated metabolic syndrome. Oxidative stress increases the lipid peroxidation product, 4-hydroxynonenal (4-HNE), which is one of the most abundant and active lipid peroxides. Within the adipose tissue, adipocytes are derived from adipose tissue-derived stromal cells (ADSCs), which play a key role in the generation and metabolism of adipose tissue. Additionally, obesity is associated with low-grade inflammation. Specific microRNAs (miRNAs) that regulate obesity-associated inflammation are largely dysregulated in metabolic syndrome (MS). In this study, we aim to confirm whether 4-HNE and miRNAs play a role in the regulation of TNF-α gene transcription. We enrolled six obese individuals who were referred to Harbin Medical University (Heilongjiang, China) and six nonobese control participants. Plasma 4-HNE levels of the 12 subjects were determined by ELISA. Using qRT-PCR, we measured ETS1, miR-29b, SP1, and TNF-α levels in subcutaneous white adipose tissue (WAT). Furthermore, we examined the relationship between ETS1 and TNF-α using a luciferase reporter assay and a ChIP assay. Our results suggest that ETS1 promotes TNF-α gene transcription in adipocytes. In addition, we demonstrated that 4-HNE promotes TNF-α gene transcription through the inhibition of the miR-29b → SP1 → TNF-α pathway and promotion of the ETS1 → TNF-α pathway. Anat Rec, 299:1145-1152, 2016. © 2016 Wiley Periodicals, Inc. PMID:27164408

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

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda; Kastrup, Jens; Simonsen, Ulf; Zachar, Vladimir; Fink, Trine

    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...... (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. Adipose mesenchymal stem cells isolated after manual or water jet-assisted liposuction display similar properties

    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.

  2. Treatment of Pseudoangiomatous Stromal Hyperplasia of the Breast: Implant-Based Reconstruction with a Vascularized Dermal Sling.

    Jung, Bok Ki; Nahm, Ji Hae; Lew, Dae Hyun; Lee, Dong Won

    2015-09-01

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal lesion with incidental histologic findings. Surgical excision is recommended as the treatment of choice for PASH, although the recurrence rates after excision range from 15% to 22%. A 46-year-old-female presented with a six-month history of bilateral breast enlargement and painful sensation mimicking inflammatory carcinoma. Imaging studies demonstrated innumerable enhancing nodules in both breasts. Due to the growth of the lesions and progressive clinical symptoms, bilateral subcutaneous mastectomy was performed. Grossly, the specimens were round and well-circumscribed, and the histologic examination revealed PASH. After mastectomy, we created a pocket with the pectoralis major muscle and a lower skin flap, which was deepithelized. Anatomical mammary implants were inserted, and the nipple areolar complex was transferred to a new position as a free graft. The aesthetic result was satisfactory after twelve months of follow-up. PMID:26430637

  3. Boosting angiogenesis and functional vascularization in injectable dextran-hyaluronic acid hydrogels by endothelial-like mesenchymal stromal cells

    Portalska, K.K.; Moreira Teixeira, L.S.; Leijten, J.C.H.; Jin, R.; Blitterswijk, van C.A.; Boer, de J.; Karperien, H.B.J.

    2014-01-01

    Angiogenesis and neo-vascularization are fundamental for the success of clinically relevant- sized tissue engineered (TE) constructs. The next generation of TE constructs relies on providing instructive materials combined with the delivery of angiogenic growth factors and cells to avoid tissue ische

  4. [Morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life from mothers that do not follow a healthy lifestyle

    Gorianikova I.N.

    2015-01-01

    Background. Morphofunctional state of the thymus of child in most cases is directly dependent on the mother health and her lifestyle. Objective. The purpose of the research was to reveal the morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life born from women who conducted a sedentary lifestyle, smoked, drank alcohol and ate the foods containing tartrazine. Methods. The material of the study was 67 thymuses of stillborn c...

  5. Three-Dimensional Cell Culture of Vascular Networks on Biomimetic Hydrogel Scaffolds

    Hulkkonen, Hanna

    2015-01-01

    In vitro modeling of vascular development (angiogenesis) remains challenging since cell behavior may be abnormal in traditional, simplified monocultures. To mimic the extracellular matrix, 3D-printed and uniform fibrin and fibrin/gelatin hydrogels were fabricated to support capillary morphogenesis of human endothelial cells and adipose stromal cells. A microextrusion method was optimized for printing of patterned hydrogels. The effects of topography and hydrogel formulation on capillary l...

  6. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

    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.

  7. Verification of suitable and reliable reference genes for quantitative real-time PCR during adipogenic differentiation in porcine intramuscular stromal-vascular cells.

    Li, X; Huang, K; Chen, F; Li, W; Sun, S; Shi, X-E; Yang, G

    2016-06-01

    Intramuscular fat (IMF) is an important trait influencing meat quality, and intramuscular stromal-vascular cell (MSVC) differentiation is a key factor affecting IMF deposition. Quantitative real-time PCR (qPCR) is often used to screen the differentially expressed genes during differentiation of MSVCs, where proper reference genes are essential. In this study, we assessed 31 of previously reported reference genes for their expression suitability in porcine MSVCs derived form longissimus dorsi with qPCR. The expression stability of these genes was evaluated using NormFinder, geNorm and BestKeeper algorithms. NormFinder and geNorm uncovered ACTB, ALDOA and RPS18 as the most three stable genes. BestKeeper identified RPL13A, SSU72 and DAK as the most three stable genes. GAPDH was found to be the least stable gene by all of the three software packages, indicating it is not an appropriate reference gene in qPCR assay. These results might be helpful for further studies in pigs that explore the molecular mechanism underlying IMF deposition. PMID:26781521

  8. Loss-of-Function of HtrA1 Abrogates All-Trans Retinoic Acid-Induced Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in p70S6K Activation.

    Glanz, Stephan; Mirsaidi, Ali; López-Fagundo, Cristina; Filliat, Gladys; Tiaden, André N; Richards, Peter J

    2016-05-01

    All-trans retinoic acid (ATRA) is a potent inducer of osteogenic differentiation in mouse adipose-derived stromal cells (mASCs), although the underlying mechanisms responsible for its mode of action have yet to be completely elucidated. High temperature requirement protease A1 (HtrA1) is a newly recognized modulator of human multipotent stromal cell (MSC) osteogenesis and as such, may play a role in regulating ATRA-dependent osteogenic differentiation of mASCs. In this study, we assessed the influence of small interfering RNA (siRNA)-induced repression of HtrA1 production on mASC osteogenesis and examined its effects on ATRA-mediated mammalian target of rapamycin (mTOR) signaling. Inhibition of HtrA1 production in osteogenic mASCs resulted in a significant reduction of alkaline phosphatase activity and mineralized matrix formation. Western blot analyses revealed the rapid activation of Akt (Ser473) and p70S6K (Thr389) in ATRA-treated mASCs, and that levels of phosphorylated p70S6K were noticeably reduced in HtrA1-deficient mASCs. Further studies using mTOR inhibitor rapamycin and siRNA specific for the p70S6K gene Rps6kb1 confirmed ATRA-mediated mASC osteogenesis as being dependent on p70S6K activation. Finally, transfection of cells with a constitutively active rapamycin-resistant p70S6K mutant could restore the mineralizing capacity of HtrA1-deficient mASCs. These findings therefore lend further support for HtrA1 as a positive mediator of MSC osteogenesis and provide new insights into the molecular mode of action of ATRA in regulating mASC lineage commitment. PMID:26950191

  9. Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction.

    Manimaran, K; Sharma, Rohini; Sankaranarayanan, S; Perumal, S Mahendra

    2016-01-01

    Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. PMID:27563616

  10. Reduction in visceral adiposity is highly related to improvement in vascular endothelial dysfunction among obese women: an assessment of endothelial function by radial artery pulse wave analysis.

    Park, Si-Hoon; Shim, Kyung-Won

    2005-08-31

    Because obesity is frequently complicated by other cardiovascular risk factors, the impact of a reduction in visceral adiposity on vascular endothelial dysfunction (VED) in obese patients is difficult to determine. In the present study, we evaluated the impact of a reduction in visceral adiposity on VED in obese women. Thirty-six premenopausal obese women (BMI >/= 25 kg/m2) without complications were enrolled in the study. VED was evaluated by determining the augmentation index (AIx) from radial artery pulse waves obtained by applanation tonometry. Changes in AIx in response to nitroglycerin- induced endothelium-independent vasodilatation (DeltaAIx-NTG) and in response to salbutamol administration (DeltaAIx-Salb) were determined before and after weight reduction. After a 12-week weight reduction program, the average weight loss was 7.96 +/- 3.47 kg, with losses of 21.88 +/- 20.39 cm2 in visceral fat areas (p analysis combined with provocative pharmacological testing demonstrated preserved endothelium-independent vasodilation in healthy premenopausal obese women (DeltaAIx-NTG: 31.36 +/- 9.80% before weight reduction vs. 28.25 +/- 11.21% after weight reduction, p > 0.1) and an improvement in endothelial-dependent vasodilation following weight reduction (DeltaAIx-Salb: 10.03 +/- 6.49% before weight reduction vs. 19.33 +/- 9.28% after reduction, p VED. This finding suggests that reduction of visceral adiposity may be as important as the control of other major risk factors in the prevention of atherosclerosis in obese women. PMID:16127776

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

    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. PMID:26888598

  12. Polyurethane/Polylactide-Blend Films Doped with Zinc Ions for the Growth and Expansion of Human Olfactory Ensheathing Cells (OECs and Adipose-Derived Mesenchymal Stromal Stem Cells (ASCs for Regenerative Medicine Applications

    Krzysztof Marycz

    2016-04-01

    Full Text Available Polymeric biomaterials based on polyurethane and polylactide blends are promising candidates for regenerative medicine applications as biocompatible, bioresorbable carriers. In current research we showed that 80/20 polyurethane/polylactide blends (PU/PLDL with confirmed biological properties in vitro may be further improved by the addition of ZnO nanoparticles for the delivery of bioactive zinc oxide for cells. The PU/PLDL blends were doped with different concentrations of ZnO (0.001%, 0.01%, 0.05% and undertaken for in vitro biological evaluation using human adipose stromal stem cells (ASCs and olfactory ensheathing cells (OECs. The addition of 0.001% of ZnO to the biomaterials positively influenced the morphology, proliferation, and phenotype of cells cultured on the scaffolds. Moreover, the analysis of oxidative stress markers revealed that 0.001% of ZnO added to the material decreased the stress level in both cell lines. In addition, the levels of neural-specific genes were upregulated in OECs when cultured on sample 0.001 ZnO, while the apoptosis-related genes were downregulated in OECs and ASCs in the same group. Therefore, we showed that PU/PLDL blends doped with 0.001% of ZnO exert beneficial influence on ASCs and OECs in vitro and they may be considered for future applications in the field of regenerative medicine.

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

    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

  14. [Morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life from mothers that do not follow a healthy lifestyle

    Gorianikova I.N.

    2015-09-01

    Full Text Available Background. Morphofunctional state of the thymus of child in most cases is directly dependent on the mother health and her lifestyle. Objective. The purpose of the research was to reveal the morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life born from women who conducted a sedentary lifestyle, smoked, drank alcohol and ate the foods containing tartrazine. Methods. The material of the study was 67 thymuses of stillborn children and children under one year of life born from mothers who conducted a sedentary lifestyle, smoked, drank alcohol and ate the foods containing tartrazine. Results. It was found that the above mentioned components of mother lifestyle are damaging factors for thymus of their children that lead to structural changes in the walls of microcirculatory blood vessels, circulatory disorders, sclerotic and atrophic changes in the organ. Structural changes in the vascular endothelium (swelling, desquamation, wall of the vessel (focal thickening of the basement membrane, thickening of the vessel wall, sclerotic and atrophic processes in the thymus increased with increasing age of the child. The severity of the circulatory disorders (vascular hyperemia, hemorrhage, edema, thrombus formation decreased with increasing age of the child. Conclusion. An important step to prevent the structural changes in children from mothers with unhealthy lifestyles is pregravid preparation including conscious following the rules of healthy lifestyle, formation the moral responsibility and willingness to pregnancy. Citation: Gorianikova IN. [Morphological features of stromal-vascular component of the thymus of stillborn children and children under one year of life from mothers that do not follow a healthy lifestyle]. Morphologia. 2015;9(3:12-7. Russian.

  15. Sclerosing stromal tumour of ovary

    Chitrawati B. Gargade

    2016-06-01

    Full Text Available Sclerosing stromal tumor is rare benign ovarian sex cord stromal tumour which occurs predominantly in the 2nd and 3rd decades of life. We report a case of a 32-year-old woman who presented with irregular menstruation and pelvic pain. She underwent panhysterectomy as USG revealed a solid and cystic 15 cm right ovarian tumour with increased vascularity with raised CA125. Hysterectomy specimen revealed a benign sclerosing stromal tumour of right ovary. We present this rare case to emphasis the awareness of benign sclerosing stromal tumour of ovary in young female to avoid unnecessary extensive surgery. [Int J Reprod Contracept Obstet Gynecol 2016; 5(6.000: 2037-2040

  16. Enrichment of IFN-γ producing cells in different murine adipose tissue depots upon infection with an apicomplexan parasite

    Teixeira, Luzia; Marques, Raquel M.; Ferreirinha, Pedro; Bezerra, Filipa; Melo, Joana; Moreira, João; Pinto, Ana; Correia, Alexandra; Ferreira, Paula G.; Vilanova, Manuel

    2016-01-01

    Here we report that lean mice infected with the intracellular parasite Neospora caninum show a fast but sustained increase in the frequency of IFN-γ-producing cells noticeable in distinct adipose tissue depots. Moreover, IFN-γ-mediated immune memory could be evoked in vitro in parasite antigen-stimulated adipose tissue stromal vascular fraction cells collected from mice infected one year before. Innate or innate-like cells such as NK, NK T and TCRγδ+ cells, but also CD4+ and CD8+ TCRβ+ lymphocytes contributed to the IFN-γ production observed since day one of infection. This early cytokine production was largely abrogated in IL-12/IL23 p40-deficient mice. Moreover, production of IFN-γ by stromal vascular fraction cells isolated from these mice was markedly lower than that of wild-type counterparts upon stimulation with parasite antigen. In wild-type mice the increased IFN-γ production was concomitant with up-regulated expression of genes encoding interferon-inducible GTPases and nitric oxide synthase, which are important effector molecules in controlling intracellular parasite growth. This increased gene expression was markedly impaired in the p40-deficient mice. Overall, these results show that NK cells but also diverse T cell populations mediate a prompt and widespread production of IFN-γ in the adipose tissue of N. caninum infected mice. PMID:27001522

  17. Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1.

    Ying Lyu

    Full Text Available Perilipin 1 (Plin1 localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human. This study investigated the roles of Plin1 in adipocyte differentiation. Plin1 null (-/- mice showed plenty of multilocular adipocytes and small unilocular adipocytes in adipose tissue, along with lack of a subpopulation of adipose progenitor cells capable of in vivo adipogenesis and along with downregulation of adipogenic pathway. Before initiation of differentiation, adipose stromal-vascular cells (SVCs from Plin1-/- mice already accumulated numerous tiny lipid droplets, which increased in number and size during the first 12-h induction but thereafter became disappeared at day 1 of differentiation. The adipogenic signaling was dysregulated despite protein level of PPARγ was near normal in Plin1-/- SVCs like in Plin1-/- adipose tissue. Heterozygous Plin1+/- SVCs were able to develop lipid droplets, with both the number and size more than in Plin1-/- SVCs but less than in Plin1+/+ SVCs, indicating that Plin1 haploinsufficiency accounts for attenuated adipogenesis. Aberrant lipid droplet growth and differentiation of Plin1-/- SVCs were rescued by adenoviral Plin1 expression and were ameliorated by enhanced or prolonged adipogenic stimulation. Our finding suggests that Plin1 plays an important role in adipocyte differentiation and provides an insight into the pathology of partial lipodystrophy in patients with Plin1 mutation.

  18. Characterization of DLK1(PREF1+/CD34+ cells in vascular stroma of human white adipose tissue

    Marit E. Zwierzina

    2015-09-01

    Full Text Available Sorting of native (unpermeabilized SVF-cells from human subcutaneous (sWAT for cell surface staining (cs of DLK1 and CD34 identified three main populations: ~10% stained cs-DLK1+/cs-CD34−, ~20% cs-DLK1+/cs-CD34+dim and ~45% cs-DLK1−/cs-CD34+. FACS analysis after permeabilization showed that all these cells stained positive for intracellular DLK1, while CD34 was undetectable in cs-DLK1+/cs-CD34− cells. Permeabilized cs-DLK1−/cs-CD34+ cells were positive for the pericyte marker α-SMA and the mesenchymal markers CD90 and CD105, albeit CD105 staining was dim (cs-DLK1−/cs-CD34+/CD90+/CD105+dim/α-SMA+/CD45−/CD31−. Only these cells showed proliferative and adipogenic capacity. Cs-DLK1+/cs-CD34− and cs-DLK1+/cs-CD34+dim cells were also α-SMA+ but expressed CD31, had a mixed hematopoietic and mesenchymal phenotype, and could neither proliferate nor differentiate into adipocytes. Histological analysis of sWAT detected DLK1+/CD34+ and DLK1+/CD90+ cells mainly in the outer ring of vessel-associated stroma and at capillaries. DLK1+/α-SMA+ cells were localized in the CD34− perivascular ring and in adventitial vascular stroma. All these DLK1+ cells possess a spindle-shaped morphology with extremely long processes. DLK1+/CD34+ cells were also detected in vessel endothelium. Additionally, we show that sWAT contains significantly more DLK1+ cells than visceral (vWAT. We conclude that sWAT has more DKL1+ cells than vWAT and contains different DLK1/CD34 populations, and only cs-DLK1−/cs-CD34+/CD90+/CD105+dim/α-SMA+/CD45−/CD31− cells in the adventitial vascular stroma exhibit proliferative and adipogenic capacity.

  19. Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model.

    Guihua Liu

    Full Text Available The aim of this study was to determine whether adipose derived stem cells (ADSCs expressing vascular endothelial growth factor (VEGF gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg, and then screened by apomorphine (100 µg/kg. Five groups were used (n = 12/group-Group 1 (G1: intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1-G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP and intracavernosal pressure (ICP were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01 than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF, smooth muscle markers (a-actin and smoothelin, and pericyte markers (CD146 and NG2. ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.

  20. Hypoxia promotes adipose-derived stem cell proliferation via VEGF

    Phuc Van Pham

    2016-01-01

    Full Text Available Adipose-derived stem cells (ADSCs are a promising mesenchymal stem cell source with therapeutic applications. Recent studies have shown that ADSCs could be expanded in vitro without phenotype changes. This study aimed to evaluate the effect of hypoxia on ADSC proliferation in vitro and to determine the role of vascular endothelial growth factor (VEGF in ADSC proliferation. ADSCs were selectively cultured from the stromal vascular fraction obtained from adipose tissue in DMEM/F12 medium supplemented with 10% fetal bovine serum and 1% antibiotic-antimycotic. ADSCs were cultured under two conditions: hypoxia (5% O2 and normal oxygen (21% O2. The effects of the oxygen concentration on cell proliferation were examined by cell cycle and doubling time. The expression of VEGF was evaluated by the ELISA assay. The role of VEGF in ADSC proliferation was studied by neutralizing VEGF with anti-VEGF monoclonal antibodies. We found that the ADSC proliferation rate was significantly higher under hypoxia compared with normoxia. In hypoxia, ADSCs also triggered VEGF expression. However, neutralizing VEGF with anti-VEGF monoclonal antibodies significantly reduced the proliferation rate. These results suggest that hypoxia stimulated ADSC proliferation in association with VEGF production. [Biomed Res Ther 2016; 3(1.000: 476-482

  1. Adenovirus-mediated transfer of VEGF into marrow stromal cells combined with PLGA/TCP scaffold increases vascularization and promotes bone repair in vivo

    Duan, Chunguang; Liu, Jian; YUAN, ZHI; Meng, Guolin; Yang, Xiumei; Jia, Shuaijun; Zhang, Jinkang; Chen, Shi

    2012-01-01

    Introduction Large osseous defect remains a serious clinical problem due to the lack of sufficient blood supply and it has been proposed that this situation can be relieved by accelerating the formation of new vessels in the process of bone defect repair. The aim of this study was to develop a new type of artificial bone by transferring the VEGF gene into marrow stromal cells (MSCs) and seeding them into a porous scaffold. Material and methods An adenovirus vector was employed to transfer the...

  2. Pseudoangiomatous stromal hyperplasia: a case report.

    Masannat, Yazan A; Whitehead, Stephen; Hawley, Ian; Apthorp, Lesley; Shah, Elizabeth F

    2010-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferating breast condition. It was first reported in 1986 when Vuitch, Rosen, and Erlandson described nine cases of benign well-circumscribed, breast masses that simulated vascular lesions consisting of mammary stromal proliferations (Vuitch et al. (1986)). Since then there have been few reported cases of PASH in the literature (Taira et al. (2005)). We describe a large PASH, mimicking inflammatory carcinoma in a young lady that was excised with excellent cosmetic results. PMID:21318179

  3. Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth.

    To, Catherine; Farnsworth, Rae H; Vail, Mary E; Chheang, Chanly; Gargett, Caroline E; Murone, Carmel; Llerena, Carmen; Major, Andrew T; Scott, Andrew M; Janes, Peter W; Lackmann, Martin

    2014-01-01

    Eph and ephrin proteins are essential cell guidance cues that orchestrate cell navigation and control cell-cell interactions during developmental tissue patterning, organogenesis and vasculogenesis. They have been extensively studied in animal models of embryogenesis and adult tissue regeneration, but less is known about their expression and function during human tissue and organ regeneration. We discovered the hypoxia inducible factor (HIF)-1α-controlled expression of EphA3, an Eph family member with critical functions during human tumour progression, in the vascularised tissue of regenerating human endometrium and on isolated human endometrial multipotent mesenchymal stromal cells (eMSCs), but not in other highly vascularised human organs. EphA3 affinity-isolation from human biopsy tissue yielded multipotent CD29+/CD73+/CD90+/CD146+ eMSCs that can be clonally propagated and respond to EphA3 agonists with EphA3 phosphorylation, cell contraction, cell-cell segregation and directed cell migration. EphA3 silencing significantly inhibited the ability of transplanted eMSCs to support neovascularisation in immunocompromised mice. In accord with established roles of Eph receptors in mediating interactions between endothelial and perivascular stromal cells during mouse development, our findings suggest that HIF-1α-controlled expression of EphA3 on human MSCs functions during the hypoxia-initiated early stages of adult blood vessel formation. PMID:25420155

  4. Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth.

    Catherine To

    Full Text Available Eph and ephrin proteins are essential cell guidance cues that orchestrate cell navigation and control cell-cell interactions during developmental tissue patterning, organogenesis and vasculogenesis. They have been extensively studied in animal models of embryogenesis and adult tissue regeneration, but less is known about their expression and function during human tissue and organ regeneration. We discovered the hypoxia inducible factor (HIF-1α-controlled expression of EphA3, an Eph family member with critical functions during human tumour progression, in the vascularised tissue of regenerating human endometrium and on isolated human endometrial multipotent mesenchymal stromal cells (eMSCs, but not in other highly vascularised human organs. EphA3 affinity-isolation from human biopsy tissue yielded multipotent CD29+/CD73+/CD90+/CD146+ eMSCs that can be clonally propagated and respond to EphA3 agonists with EphA3 phosphorylation, cell contraction, cell-cell segregation and directed cell migration. EphA3 silencing significantly inhibited the ability of transplanted eMSCs to support neovascularisation in immunocompromised mice. In accord with established roles of Eph receptors in mediating interactions between endothelial and perivascular stromal cells during mouse development, our findings suggest that HIF-1α-controlled expression of EphA3 on human MSCs functions during the hypoxia-initiated early stages of adult blood vessel formation.

  5. The Adipose Tissue in Farm Animals

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura;

    2014-01-01

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

  6. Identification of a common reference gene pair for qPCR in human mesenchymal stromal cells from different tissue sources treated with VEGF

    Tratwal, Josefine; Follin, Bjarke; Ekblond, Annette; Kastrup, Jens; Haack-Sørensen, Mandana

    2014-01-01

    ASCs are manifold and in vitro pretreatment of the cells with growth factors has been applied to potentially enhance these properties. When characterizing the transcriptional activity of these cellular mechanisms in vitro it is important to consider the effect of the growth factor treatment on......BACKGROUND: Human mesenchymal stromal cells from the bone marrow (BMSCs) are widely used as experimental regenerative treatment of ischemic heart disease, and the first clinical trials using adipose-derived stromal cells (ASCs) are currently being conducted. Regenerative mechanisms of BMSCs and...... reference genes (RGs) for the normalization of qPCR data. RESULTS: BMSCs and ASCs were stimulated with vascular endothelial growth factor A-165 (VEGF) for one week, and compared with un-stimulated cells from the same donor. The stability of nine RGs through VEGF treatment as well as the donor variation was...

  7. Human stromal (mesenchymal) stem cells

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May;

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  8. Mesenchymal markers on human adipose stem/progenitor cells

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    The stromal-vascular fraction (SVF) of adipose tissue is a rich source of multipotent stem cells. We and others have described 3 major populations of stem/progenitor cells in this fraction, all closely associated with small blood vessels: endothelial progenitor cells (EPC, CD45−/CD31+/CD34+), pericytes (CD45−/CD31−/CD146+) and supra-adventitial adipose stromal cells (SA-ASC, CD45−/CD31−/CD146−/CD34+). EPC are luminal, pericytes are adventitial and SA-ASC surround the vessel like a sheath. The multipotency of the pericytes and SA-ASC compartments is strikingly similar to that of CD45−/CD34−/CD73+/CD105+/CD90+ bone marrow-derived mesenchymal stem cells (BM-MSC). Here we determine the extent to which this mesenchymal expression pattern is expressed on the 3 adipose stem/progenitor populations. Eight independent adipose tissue samples were analyzed in a single tube (CD105-FITC/CD73-PE/CD146-PETXR/CD14-PECY5/CD33-PECY5/CD235A-PECY5/CD31-PECY7/CD90-APC/CD34-A700/CD45-APCCY7/DAPI). Adipose EPC were highly proliferative with 14.3±2.8% (mean ± SEM) having >2N DNA. About half (53.1±7.6%) coexpressed CD73 and CD105, and 71.9±7.4% expressed CD90. Pericytes were less proliferative (8.2±3.4% >2N DNA) with a smaller proportion (29.6±6.9% CD73+/CD105+, 60.5±10.2% CD90+) expressing mesenchymal associated markers. However, the CD34+ subset of CD146+ pericytes, were both highly proliferative (15.1±3.6% with >2N DNA) and of uniform mesenchymal phenotype (93.3±3.7% CD73+/CD105+, 97.8±0.7% CD90+), suggesting transit amplifying progenitor cells. SA-ASC were the least proliferative (3.7 ± 0.8%>2N DNA) but were also highly mesenchymal in phenotype (94.4±3.2% CD73+/CD105+, 95.5±1.2% CD90+). These data imply a progenitor/progeny relationship between pericytes and SA-ASC, the most mesenchymal of SVF cells. Despite phenotypic and functional similarities to BM-MSC, SA-ASC are distinguished by CD34 expression. PMID:23184564

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

    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

  10. Nck2 Deficiency in Mice Results in Increased Adiposity Associated With Adipocyte Hypertrophy and Enhanced Adipogenesis.

    Dusseault, Julie; Li, Bing; Haider, Nida; Goyette, Marie-Anne; Côté, Jean-François; Larose, Louise

    2016-09-01

    Obesity results from an excessive expansion of white adipose tissue (WAT) from hypertrophy of preexisting adipocytes and enhancement of precursor differentiation into mature adipocytes. We report that Nck2-deficient mice display progressive increased adiposity associated with adipocyte hypertrophy. A negative relationship between the expression of Nck2 and WAT expansion was recapitulated in humans such that reduced Nck2 protein and mRNA levels in human visceral WAT significantly correlate with the degree of obesity. Accordingly, Nck2 deficiency promotes an adipogenic program that not only enhances adipocyte differentiation and lipid droplet formation but also results in dysfunctional elevated lipogenesis and lipolysis activities in mouse WAT as well as in stromal vascular fraction and 3T3-L1 preadipocytes. We provide strong evidence to support that through a mechanism involving primed PERK activation and signaling, Nck2 deficiency in adipocyte precursors is associated with enhanced adipogenesis in vitro and adiposity in vivo. Finally, in agreement with elevated circulating lipids, Nck2-deficient mice develop glucose intolerance, insulin resistance, and hepatic steatosis. Taken together, these findings reveal that Nck2 is a novel regulator of adiposity and suggest that Nck2 is important in limiting WAT expansion and dysfunction in mice and humans. PMID:27325288

  11. In vivo therapeutic potential of mesenchymal stromal cells depends on the source and the isolation procedure.

    Bortolotti, Francesca; Ukovich, Laura; Razban, Vahid; Martinelli, Valentina; Ruozi, Giulia; Pelos, Barbara; Dore, Franca; Giacca, Mauro; Zacchigna, Serena

    2015-03-10

    Over the last several years, mesenchymal stromal cells (MSCs) have been isolated from different tissues following a variety of different procedures. Here, we comparatively assess the ex vivo and in vivo properties of MSCs isolated from either adipose tissue or bone marrow by different purification protocols. After MSC transplantation into a mouse model of hindlimb ischemia, clinical and histological analysis revealed that bone marrow MSCs purified on adhesive substrates exerted the best therapeutic activity, preserving tissue viability and promoting formation of new arterioles without directly transdifferentiating into vascular cells. In keeping with these observations, these cells abundantly expressed cytokines involved in vessel maturation and cell retention. These findings indicate that the choice of MSC source and purification protocol is critical in determining the therapeutic potential of these cells and warrant the standardization of an optimal MSC isolation procedure in order to select the best conditions to move forward to more effective clinical experimentation. PMID:25660405

  12. Equine deep stromal abscesses (51 cases - 2004-2009) - Part 1

    Henriksen, Michala de Linde; Andersen, Pia H.; Thomsen, Preben Dybdahl; Plummer, Caryn E.; Mangan, Brendan; Heegaard, Steffen; Toft, Nils; Brooks, Dennis E.

    To study the equine deep stromal abscesses (DSA) with focus on the duration of the corneal disease, medical treatment, season of presentation, clinical appearance, and the degree of corneal vascularization.......To study the equine deep stromal abscesses (DSA) with focus on the duration of the corneal disease, medical treatment, season of presentation, clinical appearance, and the degree of corneal vascularization....

  13. Visceral adiposity syndrome.

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M

    2016-01-01

    The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of

  14. In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells

    Vishnubalaji Radhakrishnan

    2012-01-01

    Full Text Available Abstract Background Multipotent stem cells have been successfully isolated from various tissues and are currently utilized for tissue-engineering and cell-based therapies. Among the many sources, skin has recently emerged as an attractive source for multipotent cells because of its abundance. Recent literature showed that skin stromal cells (SSCs possess mesoderm lineage differentiation potential; however, the endothelial differentiation and angiogenic potential of SSC remains elusive. In our study, SSCs were isolated from human neonatal foreskin (hNFSSCs and adult dermal skin (hADSSCs using explants cultures and were compared with bone marrow (hMSC-TERT and adipose tissue-derived mesenchymal stem cells (hADMSCs for their potential differentiation into osteoblasts, adipocytes, and endothelial cells. Results Concordant with previous studies, both MSCs and SSCs showed similar morphology, surface protein expression, and were able to differentiate into osteoblasts and adipocytes. Using an endothelial induction culture system combined with an in vitro matrigel angiogenesis assay, hNFSSCs and hADSSCs exhibited the highest tube-forming capability, which was similar to those formed by human umbilical vein endothelial cells (HUVEC, with hNFSSCs forming the most tightly packed, longest, and largest diameter tubules among the three cell types. CD146 was highly expressed on hNFSSCs and HUVEC followed by hADSSCs, and hMSC-TERT, while its expression was almost absent on hADMSCs. Similarly, higher vascular density (based on the expression of CD31, CD34, vWF, CD146 and SMA was observed in neonatal skin, followed by adult dermal skin and adipose tissue. Thus, our preliminary data indicated a plausible relationship between vascular densities, and the expression of CD146 on multipotent cells derived from those tissues. Conclusions Our data is the first to demonstrate that human dermal skin stromal cells can be differentiated into endothelial lineage. Hence, SSCs

  15. BMP2基因修饰犬脂肪源性基质细胞修复自体大段骨缺损%Repairing canine segmental bone defects using BMP2 gene modified adipose-derived stromal cells

    李慧武; 戴尅戎; 汤亭亭; 张晓玲; 唐坚; 孙晓江; 张双燕; 楼觉人

    2008-01-01

    Objective To evaluate osteogenetic effectiveness of porous β-tricalcium phosphate(β-TCP) ceramic mixed with human bone morphogenetic protein2 gene(Adv-hBMP2)modified adipose derived stromal cells (ADSCs) in the repair of critical-sized bone defects..Methods The ADSCs taken from the back of beagle dogs were modified by the BMP2 gene.The expression and bone-induction ability of BMP2 was identified by ELISA and ectopic bone formation in nude mice.The cells were applied to a β-tricalcium phosphate (TGP)carrier and implanted into ulnar bone defects in the canine model.18 ulnar bone defects were divided into three groups randomly and filled with granular TCP alone,granular TCP and ADSCs,or TCP and ADSCs transduced with Adv-hBMP2 respectively.All dogs were followed clinically and roentgenographically for 16 weeks and then sacrificed.Results ELISA and ectopic bone formation in nude mice showed the recombinant ADSCs could express BMP2 highly and stably.No bone defects healed after implanting granular TCP alone or granular TCP and ADSCs.In the TCP and ADSCs transduced with AdvhBMP2 group,two defects healed,four partly healed.Histological examination showed woven bone at the both end of the cortices but entirelv fibrous tissue in the middle in which defects filled with TCP alone or TCP and ADSCs.Defects filled with TCP and transduced ADSCs showed substatial new bone formation.Histomorphometry showed TCP combined with ADSCs did not significantly increase new bone area compared with TCP alone.TCP and recombinant ADSCs produced a significant increase in newly formed bone area.Conclusion ADSCs tansduced with BMP2 gene in a TCP carrier can enhance bone regeneratmn to repair the critically-sized bone defect.%目的 评价BMP2基因修饰的犬脂肪源性基质细胞(ADSCs)与β-磷酸三钙(β-TCP)复合修复自体大段骨缺损的疗效.方法 从比格犬背部脂肪组织中提取基质细胞,转染腺病毒介导的人BMP2基因(Adv-hBMP2),通过ELISA和裸鼠体

  16. Establishment of a preadipocyte cell line derived from mature adipocytes of GFP transgenic mice and formation of adipose tissue.

    Nobusue, Hiroyuki; Endo, Tsuyoshi; Kano, Koichiro

    2008-06-01

    We established a preadipocyte cell line from mature adipocytes obtained from subcutaneous fat tissue of green fluorescent protein (GFP) transgenic mice. The floating top layer, containing mature adipocytes, was isolated from subcutaneous fat tissue by collagenase digestion and filtration. Fluorescence-activated cell sorting and microscopic analysis revealed that the floating cell fraction comprised a highly homogeneous adipocyte population with no adipose stromal-vascular cells. Isolated mature adipocytes dedifferentiated into fibroblast-like cells and actively proliferated in ceiling culture. In vitro studies showed that the cells could redifferentiate into mature adipocytes in an identical way to 3T3-L1 preadipocytes. No changes in the differentiation pattern were observed during the propagation of our cells. They were successfully maintained and differentiated for at least 22 passages. We named these cells dedifferentiated fat (DFAT-GFP) cells. When DFAT-GFP cells were implanted subcutaneously into C57BL/6N mice, they developed highly vascularized fat pads that morphologically resembled normal subcutaneous adipose tissue and consisted of GFP-positive cells; however, implanted 3T3-L1 cells did not have such an effect on the mice. We conclude that DFAT-GFP cells provide a model that should enable us to study the mechanisms of adipocyte differentiation and adipose tissue formation in vivo and in vitro. PMID:18386066

  17. Fracción vascular estromal de tejido adiposo: cómo obtener células madre y su rendimiento de acuerdo a la topografía de las áreas donantes: estudio preliminar Fração vascular estromal de tecido adiposo: como obter células-tronco e seu rendimiento de acordo com a topografia as áreas doadoras: nota prévia Stromal vascular fraction from fat tissue: obtaining stem cells and their yield according to the topography of the donor areas: previous note

    K. A. Almeida

    2008-03-01

    least five times more colony-forming units (CFUs than bone marrow extracts. The aim of this study is to show what can be expected from fat tissues as an origin of adult stromal vascular fraction (SVF cells, and to evaluate the best areas to be elected as donor sites within the human body, all obtained by liposuction. The routine to obtain SVF cells by collagenase digestion of human adipose tissue samples was described. At the time of harvest, these cells displayed a viability of 92+/- 1% based on Trypan Blue exclusion, SVF cells were counted after 48 hours culture in Dulbecco ´s modified Eagle medium (DMEM in a Neubauer counting chamber. The average yield of SVF cells was 7,2 +/- 1,3 x 103 cells per milliliter of liposuctioned tissue. As a conclusion, best strategies to obtain SVF cells are an important challenge nowadays. This study, although preliminary, showed that SVF may be easily obtained From liposuction. Comparison among different donor sites showed a 22% higher yield of SVF cells when fat tissue had been obtained from the trunk regions, when confronted with limbs.

  18. AN EVALUATION OF THE SAFETY OF ADIPOSE-DERIVED STEM CELLS

    Ngoc Bich Vu

    2015-09-01

    Full Text Available The adipose tissue contains a large numbers of stem cells; adipose-derived stem cells (ADSCs can be em- ployed in regenerative medicine. This study was aimed at isolating ADSCs and evaluating the safety of ADSCs in mouse models. Stromal vascular fraction (SVF was collected from the adipose tissue using collagenase. ADSCs were then isolated from SVFs by in vitro culture. The stemness of the ADSCs was evaluated in vitro based on their self-renewal potential, po- tential to differentiate into osteoblasts, and adipocytes, and the expression of specific markers. Finally, the tumor forma- tion ability of ADSCs was evaluated in vivo in athymic mice. Results showed that 100% of the ADSC samples developed well and maintained homogeneity up to passage 10. The ADSCs were completely sterilized and could not form tumors in athymic mice. These initial results showed that ADSCs were safe for use in stem cell therapy. [Biomed Res Ther 2015; 2(9.000: 359-365

  19. Inflammatory cytokine gene expression in mesenteric adipose tissue during acute experimental colitis.

    W Conan Mustain

    Full Text Available BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT has been implicated in the pathogenesis of inflammatory bowel disease (IBD. Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF, and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.

  20. Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss

    Bruun, Jens M; Stallknecht, Bente; Helge, Jørn W;

    2007-01-01

    OBJECTIVE: Interleukin (IL)-18 is associated with obesity, insulin resistance, and cardiovascular disease. The present study compared 1) IL-18 in adipocytes versus stromal vascular (SV) cells, 2) IL-18 in plasma and adipose tissue (AT) in obese versus lean subjects, and 3) IL-18 in plasma, AT, and...... skeletal muscle (SM) in obese subjects after weight loss. SUBJECTS AND METHODS: At baseline, plasma and AT IL-18 in 23 obese subjects were compared with that in 12 lean subjects. The obese subjects were submitted to a 15-week life-style intervention (hypocaloric diet and daily exercise) after which plasma...... samples, AT, and SM biopsies were obtained. Analyses were performed by ELISA and RT-PCR respectively. RESULTS: IL-18 expression in isolated adipocytes was approximately 2% of that in SV cells. Plasma IL-18 was higher in obese subjects (P < 0.001) and associated with insulin resistance (HOMA; P < 0...

  1. Adiposity of calf- and yearling-fed Brangus steers raised to constant-age and constant-body weight endpoints.

    Smith, S B; Chapman, A A; Lunt, D K; Harris, J J; Savell, J W

    2007-05-01

    We tested the hypothesis that fatty acid biosynthesis and adipocyte diameter and volume would be greater in s.c. and i.m. adipose tissues of calf-fed steers than in yearling-fed steers at a constant BW, due to the greater time on feed for the calf-fed steers. Conversely, we predicted that the capacity for s.c. and i.m. preadipocytes to divide, as estimated by 3H-thymidine incorporation into DNA, would be greater in the less mature adipose tissues of calf-fed steers and in yearling-fed steers at 16 mo of age than in yearling-fed steers fed to 18 mo of age. Brangus steers were fed a corn-based finishing diet as calves (calf-fed; n = 9) or yearlings (n = 4) to 16 mo of age (CA yearling-fed); another group of yearlings (n = 5) was fed to a constant-BW end point of 530 kg (CW yearling-fed). Both groups of yearling-fed steers had free access to native pasture until 12 mo of age. At slaughter, the fifth to eighth thoracic rib section of the LM was removed, and fresh s.c. and i.m. adipose tissues were removed for in vitro incubations. There were no differences in the number of s.c. adipocytes/g or mean peak volumes of adipocytes across production groups (P > or = 0.14). However, s.c. adipose tissue of CA yearling-fed steers contained greater proportions of smaller adipocytes (<1,500 pL) than calffed or CW yearling-fed steers, and similar results were observed for i.m. adipose tissue. Acetate incorporation into total lipids was greater (P = 0.02) in s.c. adipose tissue of CA yearling-fed steers than in calf-fed or CW yearling-fed steers, and tended to be different (P = 0.10) across production groups in i.m. adipose tissue. The production system x cell fraction interaction was significant (P = 0.03) for s.c. adipose tissue DNA synthesis, which was greatest in adipocytes from CA yearling-fed steers, whereas there were no differences across production system in stromal vascular (SV) DNA synthesis. For i.m. adipose tissue, DNA synthesis was greatest in adipocytes and SV cells

  2. Transfection of adenovirus containing hepatocyte growth factor gene into adipose tissue-derived stromal cells%腺病毒介导肝细胞生长因子基因感染脂肪干细胞

    王克明; 马继光; 栾杰

    2011-01-01

    目的 观察腺病毒介导的肝细胞生长因子(Ad-HGF)对脂肪干细胞的感染效率以及感染后是否可形成有效的肝细胞生长因子(HGF),确定感染强度(MOI)值.方法 利用消化分离方法和脂肪干细胞贴壁生长的特性,分离人脂肪干细胞,利用相同MOI的Ad-HGF感染脂肪干细胞,ELISA法检测HGF的表达.结果 脂肪干细胞均呈贴壁生长的成纤维细胞样形态,原代培养的细胞7~10 d即达70%~80%融合,Ad-HGF感染脂肪干细胞后HGF可在48 h高效表达.结论 提示腺病毒可有效介导HGF基因,可感染脂肪干细胞,并能够产生有效浓度的HGF.%Objective To observe the efficiency of infection of adenovirus containing hepatocyte growth factor(Ad-HGF) on adipose derived stem cells and to prove whether the valid HGF can appear after infection and the multiplicity of infection. Methods We use the digestion separation method and the attachingwall characteristic of the adipose-derived stem cells to separate the human adipose-derived stem cells. Adipose-derived stem cells were infected by the vector of adenovirus (Ad-GFP) which carries the GFP gene,and the GFP acts as the indicating gene to determine the infection efficiency of recombinant adenovirus to adipose- derived stem cells. HGF-ELISA was used to detect HGF as expression-secretion. Results The adherent cells displayed themselves as fibroblast in morphology. The primary cultured cells fusion can arrive to 70% - 80% in 7 - 10 days. The infected HGF can be highly expressed in 48hours. Conclusion Adenovirus can meditate the expression of HGF gene in adipose-derived stem cells effectively.

  3. In Vivo Therapeutic Potential of Mesenchymal Stromal Cells Depends on the Source and the Isolation Procedure

    Francesca Bortolotti

    2015-03-01

    Full Text Available Over the last several years, mesenchymal stromal cells (MSCs have been isolated from different tissues following a variety of different procedures. Here, we comparatively assess the ex vivo and in vivo properties of MSCs isolated from either adipose tissue or bone marrow by different purification protocols. After MSC transplantation into a mouse model of hindlimb ischemia, clinical and histological analysis revealed that bone marrow MSCs purified on adhesive substrates exerted the best therapeutic activity, preserving tissue viability and promoting formation of new arterioles without directly transdifferentiating into vascular cells. In keeping with these observations, these cells abundantly expressed cytokines involved in vessel maturation and cell retention. These findings indicate that the choice of MSC source and purification protocol is critical in determining the therapeutic potential of these cells and warrant the standardization of an optimal MSC isolation procedure in order to select the best conditions to move forward to more effective clinical experimentation.

  4. In Vivo Therapeutic Potential of Mesenchymal Stromal Cells Depends on the Source and the Isolation Procedure

    Bortolotti, Francesca; Ukovich, Laura; Razban, Vahid; Martinelli, Valentina; Ruozi, Giulia; Pelos, Barbara; Dore, Franca; Giacca, Mauro; Zacchigna, Serena

    2015-01-01

    Summary Over the last several years, mesenchymal stromal cells (MSCs) have been isolated from different tissues following a variety of different procedures. Here, we comparatively assess the ex vivo and in vivo properties of MSCs isolated from either adipose tissue or bone marrow by different purification protocols. After MSC transplantation into a mouse model of hindlimb ischemia, clinical and histological analysis revealed that bone marrow MSCs purified on adhesive substrates exerted the best therapeutic activity, preserving tissue viability and promoting formation of new arterioles without directly transdifferentiating into vascular cells. In keeping with these observations, these cells abundantly expressed cytokines involved in vessel maturation and cell retention. These findings indicate that the choice of MSC source and purification protocol is critical in determining the therapeutic potential of these cells and warrant the standardization of an optimal MSC isolation procedure in order to select the best conditions to move forward to more effective clinical experimentation. PMID:25660405

  5. Minireview: adiposity, inflammation, and atherogenesis.

    Lyon, Christopher J; Law, Ronald E; Hsueh, Willa A

    2003-06-01

    Adipose tissue is a dynamic endocrine organ that secretes a number of factors that are increasingly recognized to contribute to systemic and vascular inflammation. Several of these factors, collectively referred to as adipokines, have now been shown regulate, directly or indirectly, a number of the processes that contribute to the development of atherosclerosis, including hypertension, endothelial dysfunction, insulin resistance, and vascular remodeling. Several adipokines are preferentially expressed in visceral adipose tissue, and the secretion of proinflammatory adipokines is elevated with increasing adiposity. Not surprisingly, approaches that reduce adipose tissue depots, including surgical fat removal, exercise, and reduced caloric intake, improve proinflammatory adipokine levels and reduce the severity of their resultant pathologies. Systemic adipokine levels can also be favorably altered by treatment with several of the existing drug classes used to treat insulin resistance, hypertension, and hypercholesterolemia. Greater understanding of adipokine regulation, however, should result in the design of improved treatment strategies to control disease states associated with increase adiposity, an important outcome in view of the growing worldwide epidemic of obesity. PMID:12746274

  6. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity. PMID:27207538

  7. Cartilage tissue engineering by collagen-chitosan-chondroitin sulfate scaffold seeded with rat adipose tissue-derived stromal cells in vitro%大鼠脂肪干细胞复合胶原-壳聚糖-硫酸软骨素三维支架构建组织工程软骨

    张涛; 付勤; 于志永

    2009-01-01

    Objective To evaluate the character of the collagen-chitosan-chondroitin sulfate scaffold seeded with rat adipose tissue-derived stromal cells. Methods A dipose tissue were harvested from 6 weeks old Wistar rats and the stromal cells were harvested by type Ⅰ collagenase and then cultured in vitro. Type Ⅰ collagen was fully mixed with chitosan, freeze-dried and cross-linked with chondroitin sulfate, then freeze-dried again and sterilized by ethylene oxide. The pore diameter, water content, porosity of the scaffold were tested. The adipose tissue-derived stromal cells were digested, seeded into the plates, scaffold, and cen-trifuged into pellet, and then induced into cartilage. MTT detection for cell proliferation was done. After 3 weeks, the cell morphology, and cell proliferation and adhesion were observed, and chondrngenic differenti-ation was also analyzed. Results The pore diameter, water content, porosity tested for the scaffold showed an appropriate form. Cell proliferation showed faster in the scaffold and pellet culture system after 5 day, there was still cell proliferation in the scaffold system after 14 days but no obvious changes in the pellet cul-ture system; ceils on the scaffold proliferated densely showed by histological staining, but there was a scaf-fold structure residues in the inner layer. The finding of type Ⅱ immunohistochemistry stain showed that cells express strong positive for type Ⅱ collagen in the scaffold and pellet culture system whereas it was weakly positive in the plate culture system; the specific mRNA for cartilage, type Ⅱ collagen, aggrecan and SOX-9 were expressed in all three systems showed by RT-PCR, but type X collagen was expressed continu-ously in the plate culture system and expressed after 21 days in the pellet culture system, whereas it was not detected in the collagen-chitosan-chondroitin sulfate scaffold system. Conclusion The parameters of the collagen-chitosan-chondroitin sulfate scaffold were suitable in

  8. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype.

    Titos, Esther; Rius, Bibiana; González-Périz, Ana; López-Vicario, Cristina; Morán-Salvador, Eva; Martínez-Clemente, Marcos; Arroyo, Vicente; Clària, Joan

    2011-11-15

    We recently demonstrated that ω-3-polyunsaturated fatty acids ameliorate obesity-induced adipose tissue inflammation and insulin resistance. In this study, we report novel mechanisms underlying ω-3-polyunsaturated fatty acid actions on adipose tissue, adipocytes, and stromal vascular cells (SVC). Inflamed adipose tissue from high-fat diet-induced obese mice showed increased F4/80 and CD11b double-positive macrophage staining and elevated IL-6 and MCP-1 levels. Docosahexaenoic acid (DHA; 4 μg/g) did not change the total number of macrophages but significantly reduced the percentage of high CD11b/high F4/80-expressing cells in parallel with the emergence of low-expressing CD11b/F4/80 macrophages in the adipose tissue. This effect was associated with downregulation of proinflammatory adipokines in parallel with increased expression of IL-10, CD206, arginase 1, resistin-like molecule α, and chitinase-3 like protein, indicating a phenotypic switch in macrophage polarization toward an M2-like phenotype. This shift was confined to the SVC fraction, in which secretion of Th1 cytokines (IL-6, MCP-1, and TNF-α) was blocked by DHA. Notably, resolvin D1, an anti-inflammatory and proresolving mediator biosynthesized from DHA, markedly attenuated IFN-γ/LPS-induced Th1 cytokines while upregulating arginase 1 expression in a concentration-dependent manner. Resolvin D1 also stimulated nonphlogistic phagocytosis in adipose SVC macrophages by increasing both the number of macrophages containing ingested particles and the number of phagocytosed particles and by reducing macrophage reactive oxygen species production. No changes in adipocyte area and the phosphorylation of hormone-sensitive lipase, a rate-limiting enzyme regulating adipocyte lipolysis, were observed. These findings illustrate novel mechanisms through which resolvin D1 and its precursor DHA confer anti-inflammatory and proresolving actions in inflamed adipose tissue. PMID:22013115

  9. Effect of exercise training on the density of endothelial cells in the white adipose tissue of rats.

    Hatano, D; Ogasawara, J; Endoh, S; Sakurai, T; Nomura, S; Kizaki, T; Ohno, H; Komabayashi, T; Izawa, T

    2011-12-01

    We examined the effects of a 9-week exercise training (TR) in Wistar male rats, beginning at 4 weeks of age, on the density of endothelial cells (ECs) in epididymal white adipose tissue (WAT) and the mRNA expression of angiogenic factors in adipose tissue stromal vascular fraction (SVF) cells. The number of ECs and mRNA expressions were assessed by lectin staining and real-time reverse transcriptase-polymerase chain reaction, respectively. Compared with control (CR) rats, TR rats gained weight more slowly and had significantly lower final weight of WAT due to the reduction in the size and the number of adipocytes. TR significantly increased the number of ECs per square millimeter and per adipocyte (1.37- and 1.23-fold, respectively) in WAT. This is probably because the number of adipocytes is fewer while the number of ECs is constant in the WAT of TR rats, because the regression line of TR rats for adipocyte number-dependent EC number was shifted toward the left without significant differences in the slopes between groups. TR also induced the upregulation of mRNA expression of vascular endothelial growth factor (Vegf)-A and Vegf-receptor-2 in SVF cells, thereby retaining a constant number of ECs in the WAT. PMID:20807385

  10. Equine deep stromal abscesses (51 cases - 2004-2009) - Part 2

    Henriksen, Michala de Linde; Andersen, Pia Haubro; Mietelka, Kristy; Farina, Lisa; Thomsen, Preben Dybdahl; Plummer, Caryn E.; Mangan, Brendan G.; Heegaard, Steffen; Coleman, James K.; Toft, Nils; Brooks, Dennis E.

    To investigate histopathologic and immunohistochemical aspects of equine deep stromal abscesses (DSA) with a focus on the histopathologic diagnosis, presumptive etiology, and the immunohistochemical expression of three angiogenesis-related factors: vascular endothelial growth factor-A (VEGF...

  11. The Origin of Human Mesenchymal Stromal Cells Dictates Their Reparative Properties

    Naftali-Shani, Nili; Itzhaki-Alfia, Ayelet; Landa-Rouben, Natalie;

    2013-01-01

    Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell-based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair.......Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell-based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair....

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

    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

  13. Adipose Tissue Angiogenesis: Impact on Obesity and Type-2 Diabetes

    Corvera, Silvia; Gealekman, Olga

    2013-01-01

    The growth and function of tissues is critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in t...

  14. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

    Krzysztof Marycz

    2016-01-01

    Full Text Available Currently, equine metabolic syndrome (EMS, an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC. Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN and horses suffering from EMS (ASCEMS. ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO and reactive oxygen species (ROS in these cells, accompanied by reduced superoxide dismutase (SOD activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS.

  15. In vitro evaluation of endothelial progenitor cells from adipose tissue as potential angiogenic cell sources for bladder angiogenesis.

    Liuhua Zhou

    Full Text Available Autologous endothelial progenitor cells (EPCs might be alternative angiogenic cell sources for vascularization of tissue-engineered bladder, while isolation and culture of EPCs from peripheral blood in adult are usually time-consuming and highly inefficient. Recent evidence has shown that EPCs also exist in the adipose tissue. As adipose tissue is plentiful in the human body and can be easily harvested through a minimally invasive method, the aim of this study was to culture and characterize EPCs from adipose tissue (ADEPCs and investigate their potential for the neovascularization of tissue-engineered bladder. Adipose stromal vascular fraction (SVF was isolated and used for the culture of ADEPCs and adipose derived stem cells (ADSCs. After SVF was cultured for one week, ADEPCs with typical cobblestone morphology emerged and could be isolated from ADSCs according to their different responses to trypsinization. Rat bladder smooth muscle cells (RBSMCs were isolated and cultured from rat bladder. RBSMCs exhibited typical spindle-shaped morphology. ADEPCs had higher proliferative potential than ADSCs and RBSMCs. ADEPCs stained positive for CD34, Stro-1, VEGFR-2, eNOS and CD31 but negative for α-SMA, CD14 and CD45. ADSCs stained positive for CD34, Stro-1 and α-SMA but negative for VEGFR-2, eNOS, CD31, CD14 and CD45. RBSMCs stained only positive for α-SMA. ADEPCs could be expanded from a single cell at an early passage to a cell cluster containing more than 10,000 cells. ADEPCs were able to uptake DiI-Ac-LDL, bind UEA-1 and form capillary-like structures in three-dimensional scaffolds (Matrigel and bladder acellular matrix. ADEPCs were also able to enhance the human umbilical vein endothelial cells' capability of capillary-like tube formation on Matrigel. Additionally, significantly higher levels of mRNA and protein of vascular endothelial growth factor were found in ADEPCs than in RBSMCs. These results suggest the potential use of ADEPCs as

  16. The influence of thiazolidinediones on marbling in pigs: in vitro studies of muscle stromal-vascular cells from fetal and young pigs and in vivo studies of growing pigs

    Thiazolidinediones (TZDs) are insulin sensitizing agents currently used for the treatment of type 2 diabetes and are widely used as adipogenic agents since they are ligands of PPAR', a key adipogenic transcription factor. In vitro studies of porcine S-V cells from semitendinosus muscles and adipose ...

  17. Mesenchymal stromal cell proliferation, gene expression and protein production in human platelet-rich plasma-supplemented media.

    Paola Romina Amable

    Full Text Available BACKGROUND: Platelet-rich plasma (PRP is increasingly used as a cell culture supplement, in order to reduce the contact of human cells with animal-derived products during in vitro expansion. The effect of supplementation changes on cell growth and protein production is not fully characterized. METHODS: Human mesenchymal stromal cells from bone marrow, adipose tissue and Wharton's Jelly were isolated and cultured in PRP-supplemented media. Proliferation, in vitro differentiation, expression of cell surface markers, mRNA expression of key genes and protein secretion were quantified. RESULTS: 10% PRP sustained five to tenfold increased cell proliferation as compared to 10% fetal bovine serum. Regarding cell differentiation, PRP reduced adipogenic differentiation and increased calcium deposits in bone marrow and adipose tissue-mesenchymal stromal cells. Wharton's Jelly derived mesenchymal stromal cells secreted higher concentrations of chemokines and growth factors than other mesenchymal stromal cells when cultured in PRP-supplemented media. Bone marrow derived mesenchymal stromal cells secreted higher concentrations of pro-inflammatory and pro-angiogenic proteins. Mesenchymal stromal cells isolated from adipose tissue secreted higher amounts of extracellular matrix components. CONCLUSIONS: Mesenchymal stromal cells purified from different tissues have distinct properties regarding differentiation, angiogenic, inflammatory and matrix remodeling potential when cultured in PRP supplemented media. These abilities should be further characterized in order to choose the best protocols for their therapeutic use.

  18. Characterization of In Vitro Engineered Human Adipose Tissues: Relevant Adipokine Secretion and Impact of TNF-α

    Kim Aubin; Meryem Safoine; Maryse Proulx; Marie-Alice Audet-Casgrain; Jean-François Côté; Félix-André Têtu; Alphonse Roy; Julie Fradette

    2015-01-01

    Representative modelling of human adipose tissue functions is central to metabolic research. Tridimensional models able to recreate human adipogenesis in a physiological tissue-like context in vitro are still scarce. We describe the engineering of white adipose tissues reconstructed from their cultured adipose-derived stromal precursor cells. We hypothesize that these reconstructed tissues can recapitulate key functions of AT under basal and pro-inflammatory conditions. These tissues, featuri...

  19. Pregnancy in obese mice protects selectively against visceral adiposity and is associated with increased adipocyte estrogen signalling.

    Silvia M A Pedroni

    Full Text Available Maternal obesity is linked with increased adverse pregnancy outcomes for both mother and child. The metabolic impact of excessive fat within the context of pregnancy is not fully understood. We used a mouse model of high fat (HF feeding to induce maternal obesity to identify adipose tissue-mediated mechanisms driving metabolic dysfunction in pregnant and non-pregnant obese mice. As expected, chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral (subcutaneous and visceral (mesenteric fat mass. However, unexpectedly at late gestation (E18.5 HF-fed mice exhibited a remarkable normalization of visceral but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat mass expressed as a proportion of body weight (P<0.001. In contrast, in control animals, pregnancy had no effect on visceral fat mass proportion. Obesity exaggerated glucose intolerance at mid-pregnancy (E14.5. However by E18.5, there were no differences, in glucose tolerance between obese and control mice. Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed reduced expression of genes involved in de novo lipogenesis (diacylglycerol O-acyltransferase 2--Dgat2 and inflammation (chemokine C-C motif ligand 20--Ccl2 and upregulation of estrogen receptor α (ERα compared to HF non pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45% reduction of CD11b+CD11c+ adipose tissue macrophages (expressed as a proportion of all stromal vascular fraction cells in HF pregnant compared to HF non pregnant animals (P<0.001. An ERα selective agonist suppressed both de novo lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data show that, in a HF model of maternal obesity, late gestation is associated with amelioration of visceral fat hypertrophy, inflammation and glucose intolerance, and suggest that these effects are mediated in part by elevated visceral adipocyte ERα signaling.

  20. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation

    Fitzgibbons, Timothy P.; Kogan, Sophia; Aouadi, Myriam; Hendricks, Greg M.; Straubhaar, Juerg; Czech, Michael P.

    2011-01-01

    Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and the metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually ident...

  1. Are They Really Stem Cells? Scrutinizing the Identity of Cells and the Quality of Reporting in the Use of Adipose Tissue-Derived Stem Cells.

    Balolong, Ernesto; Lee, Soojung; Nemeno, Judee Grace; Lee, Jeong Ik

    2016-01-01

    There is an increasing concern that the term adipose tissue-derived stem cell (ASC) is inappropriately used to refer to the adipose stromal vascular fraction (SVF). To evaluate the accuracy and quality of reporting, 116 manuscripts on the application of ASC in humans and animals were examined based on the 2013 published International Federation for Adipose Therapeutics and Science (IFATS)/ International Society for Cellular Therapy (ISCT) joint statement and in reference to current guidelines for clinical trials and preclinical studies. It is disconcerting that 4 among the 47 papers or 8.51% (CI 2.37-20.38) surveyed after publication of IFATS/ISCT statement reported using ASCs but in fact they used unexpanded cells. 28/47 or 59.57% (CI 44.27-73.63) explicitly reported that adherent cells were used, 35/47 or 74.47% (CI 59.65-86.06) identified expression of surface markers, and 25/47 or 53.19% (CI 14.72-30.65) verified the multilineage potential of the cells. While there are a number of papers examined in this survey that were not able to provide adequate information on the characteristics of ASCs used with some erroneously referring to the SVF as stem cells, there are more room for improvement in the quality of reporting in the application of ASCs in humans and animals. PMID:26798353

  2. Adipose tissue macrophages in non-rodent mammals: a comparative study.

    Ampem, Grace; Azegrouz, Hind; Bacsadi, Árpád; Balogh, Lajos; Schmidt, Susanne; Thuróczy, Julianna; Röszer, Tamás

    2016-02-01

    The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals. PMID:26239911

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

    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

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

    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.

  5. Equine corneal stromal abscesses

    Henriksen, M. D. L.; Andersen, P. H.; Plummer, C. E.;

    2013-01-01

    The last 30 years have seen many changes in the understanding of the pathogenesis and treatment of equine corneal stromal abscesses (SAs). Stromal abscesses were previously considered an eye problem related to corneal bacterial infection, equine recurrent uveitis, corneal microtrauma and corneal...... thickness lamellar keratectomy to remove the fungal hyphae and diseased stroma, followed by transplantation of healthy corneal allografts has a high rate of success in speeding healing and preserving sight. This paradigm shift in the ability to diagnose and institute therapy for corneal SAs in horses has...

  6. 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

    Ithamar N. Stocchero; Gelde H.F. Stocchero; Gustavo F. Stocchero; Vivian G.Z. Stocchero; Alexandre S. F. Fonseca; Eleonora F.S. Fonseca

    2009-01-01

    Una de las situaciones más problemáticas para la vida íntima de una mujer, sobre todo si es joven, son las vulvo-vaginitis de repetición. Junto al herpes genital recidivante, suele ser causa de disarmonía en la relación de pareja por la situación en sí y por la frecuente presencia de dolor. Presentamos un caso exitoso en el que se aplicó un nuevo tratamiento consistente en la utilización de liponinjerto laminar submucoso, con preservación de la fracción vascular estromal (FVE), rica en célula...

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

    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

  8. Generation and characterization of novel stromal specific antibodies

    2005-01-01

    Rheumatoid synovial fibroblasts were used as an immunogen to produce monoclonal antibodies selected for their reactivity with stromal cell antigens. Mice were immunised with low passage whole cell preparations and the subsequent hybridomas were screened by immunohistochemistry on rheumatoid synovium and tonsil sections. The aim was to identify those antibodies that recognised antigens that were restricted to stromal cells and were not expressed on CD45 positive leucocytes. A significant number of antibodies detected antigen that identified endothelial cells. These antibodies were further characterised to determine whether the vessels identified by these antibodies were vascular or lymphatic.From five fusions clones were identified with predominant reactivity with: 1) fibroblasts and endothelial cells; or 2)broad stromal elements (fibroblast, endothelium, epithelium, follicular dendritic cells). A fibroblast-specific antibody that did not also identify vessels was not generated. Examples of each reactivity pattern are discussed.

  9. Vascular Cures

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  10. Adipose tissue fibrosis

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-01-01

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. The...

  11. Moderate doses of conjugated linoleic acid reduce fat gain, maintain insulin sensitivity without impairing inflammatory adipose tissue status in mice fed a high-fat diet

    Serra Francisca

    2010-01-01

    Full Text Available Abstract Background The enrichment of diet with nutrients with potential benefits on body composition is a strategy to combat obesity. Conjugated linoleic acid (CLA due its beneficial effects on body composition and inflammatory processes becomes an interesting candidate, since the promotion and impairment of obesity is closely linked to a low-grade inflammation state of adipose tissue. Previously we reported the favourable effects of moderate doses of CLA mixture on body composition and inflammatory status of adipose tissue in mice fed a standard-fat diet. In the present study we assessed the potential beneficial effects of CLA mixture (cis-9, trans-11 and trans-10, cis-12, 50:50 in mice fed a high-fat diet. Methods Two doses were assayed: 0.15 g (CLA1 and 0.5 g CLA/kg body weight (CLA2 for the first 30 days of the study and then animals received a double amount for another 35 days. Results The lowest dose (CLA1 had minor effects on body composition, plasma parameters and gene expression. However, a clear reduction in fat accumulation was achieved by CLA2, accompanied by a reduction in leptin, adiponectin and non-esterified fatty acids (NEFA plasma concentrations. Insulin sensitivity was maintained despite a slight increase in fasting glucose and insulin plasma concentrations. The study of gene expression both in adipocytes and in the stromal vascular fraction (SVF suggested that CLA may reduce either the infiltration of macrophages in adipose tissue or the induction of expression of pro-inflammatory cytokines. Conclusion In conclusion, the use of moderate doses of an equimolar mix of the two main CLA isomers reduces body fat content, improves plasma lipid profile, maintains insulin sensitivity (despite a moderate degree of hyperinsulinaemia without the promotion of inflammatory markers in adipose tissue of mice fed a high-fat diet.

  12. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study

    Phuc Van Pham

    2014-01-01

    Full Text Available Osteoarthritis is one of the most common diseases, and it affects 12% of the population around the world. Although the disease is chronic, it significantly reduces the patient's quality of life. At present, stem cell therapy is considered to be an efficient approach for treating this condition. Mesenchymal stem cells (MSCs show the most potential for stem cell therapy of osteoarthritis. In fact, MSCs can differentiate into certain mesodermal tissues such as cartilage and bone. Therefore, in the present study, we applied adipose tissue-derived MSCs to osteoarthritis treatment. This study aimed to evaluate the clinical efficiency of autologous adipose tissue-derived MSC transplantation in patients with confirmed osteoarthritis at grade II and III. Adipose tissue was isolated from the belly, and used for extraction of the stromal vascular fraction (SVF. The SVF was mixed with activated platelet- rich plasma before injection. The clinical efficiencies were evaluated by the pain score (VAS, Lysholm score, and MRI findings. We performed the procedure in 21 cases from 2012 to 2013. All 21 patients showed improved joint function after 8.5 months. The pain score decreased from 7.6+/-0.5 before injection to 3.5+/-0.7 at 3 months and 1.5+/-0.5 at 6 months after injection. The Lysholm score increased from 61+/-11 before injection to 82+/-8.1 after injection. Significant improvements were noted in MRI findings, with increased thickness of the cartilage layer. Moreover, there were no side-effects or complications related to microorganism infection, graft rejection, or tumorigenesis. These results provide a new opportunity for osteoarthritis treatment. Level of evidence: IV. [Biomed Res Ther 2014; 1(1.000: 02-08

  13. Skeletal (stromal) stem cells

    Abdallah, Basem M; Kermani, Abbas Jafari; Zaher, Walid;

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy for....../preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone....

  14. Stromal cell-derived factors in Duchenne muscular dystrophy

    Abdel-Salam, E.; Ehsan Abdel-Meguid, I.; Shatla, R.; Korraa, S. S.

    2010-01-01

    Duchenne muscular dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction leading to a state of functional ischemia. Abundant evidence suggests that endothelial circulating progenitor cells (EPCs) play an important role in mediating vascular and muscle repair mechanisms and that the stromal cell-derived factor (SDF)-1 α chemokine is responsible for both progenitor cell mobilization from the bone marrow to peripheral blood and homing to t...

  15. Atypical expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in subcutaneous adipose tissue of male rats.

    Thumelin, S; Kohl, C; Girard, J; Pégorier, J P

    1999-06-01

    The mRNAs encoding mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mtHMG-CoA synthase), the rate limiting enzyme in ketone body production, are highly expressed in subcutaneous (SC) and, to a lesser extent, in peri-epididymal (PE) rat adipose tissues. This atypical mtHMG-CoA synthase gene expression is dependent on the age (from 9 weeks of age) and sex (higher in male than in female) of the rats. In contrast, the expression of mtHMG-CoA synthase in SC adipose deposit is independent of the nutritional state (fed versus starved) or of the thermic environment (24 degrees C versus 4 degrees C). The expression of mtHMG-CoA synthase is suppressed in SC fat pads of castrated male rats whereas treatment of castrated rats with testosterone restores a normal level of expression. Moreover, testosterone injection induces the expression mtHMG-CoA synthase in SC adipose tissue of age-matched females. The presence of the mtHMG-CoA synthase immunoreactive protein confers to mitochondria isolated from SC adipose deposits, the capacity to produce ketone bodies at a rate similar to that found in liver mitochondria (SC = 13.7 +/- 0.7, liver = 16.4 +/- 1.4 nmol/min/mg prot). mtHMG-CoA synthase is expressed in the stromal vascular fraction (SVF) whatever the adipose deposit considered. While acetyl-CoA carboxylase (ACC) is only expressed in mature adipocytes, the other lipogenic enzymes, fatty acid synthase (FAS) and citrate cleavage enzyme (CCE), are expressed both in SVF cells and mature adipocytes. The expression of lipogenic enzyme genes is markedly reduced in adipocytes but not in SVF cells isolated from 48-h starved male rats. When SVF is subfractionated, mtHMG-CoA synthase mRNAs are mainly recovered in two fractions containing poorly digested structures such as microcapillaries whereas the lowest expression is found in the pre-adipocyte fraction. Interestingly, FAS and CCE mRNAs co-segregate with mtHMG-CoA synthase mRNA. The possible physiological relevance of such

  16. Adiponectin Enhances Cold-Induced Browning of Subcutaneous Adipose Tissue via Promoting M2 Macrophage Proliferation.

    Hui, Xiaoyan; Gu, Ping; Zhang, Jialiang; Nie, Tao; Pan, Yong; Wu, Donghai; Feng, Tianshi; Zhong, Cheng; Wang, Yu; Lam, Karen S L; Xu, Aimin

    2015-08-01

    Adiponectin is an abundant adipokine with pleiotropic protective effects against a cluster of obesity-related cardiometabolic disorders. However, its role in adaptive thermogenesis has scarcely been explored. Here we showed that chronic cold exposure led to a markedly elevated production of adiponectin in adipocytes of subcutaneous white adipose tissue (scWAT), which in turn bound to M2 macrophages in the stromal vascular fraction. Chronic cold exposure-induced accumulation of M2 macrophages, activation of beige cells, and thermogenic program were markedly impaired in scWAT of adiponectin knockout (ADN KO) mice, whereas these impairments were reversed by replenishment with adiponectin. Mechanistically, adiponectin was recruited to the cell surface of M2 macrophages via its binding partner T-cadherin and promoted the cell proliferation by activation of Akt, consequently leading to beige cell activation. These findings uncover adiponectin as a key efferent signal for cold-induced adaptive thermogenesis by mediating the crosstalk between adipocytes and M2 macrophages in scWAT. PMID:26166748

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

    Jaewoo Pak

    2016-01-01

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

  18. Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

    De Siena, Rocco; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela Gessica; Saldarelli, Marilisa [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Saponaro, Vittorio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Martino, Carmela [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Logrieco, Gaetano [Department of Surgery, Hospital ' F. Miulli' 70021 AcquaViva delle Fonti, Bari (Italy); Soleti, Antonio; Fiobellot, Simona [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Madeddu, Paolo [Experimental Cardiovascular Medicine, Bristol Heart Institute, Bristol BS2 8WH (United Kingdom); Rossi, Giacomo [Department of Pathology, University of Camerino, 63100 Ascoli Piceno (Italy); Ribatti, Domenico [Department of Human Anatomy, University of Bari, 70125 Bari (Italy); Crovace, Antonio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Cristini, Silvia; Invernici, Gloria; Parati, Eugenio Agostino [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy); Alessandri, Giulio, E-mail: cisiamo2@yahoo.com [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy)

    2010-07-01

    Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 x 10{sup 6} of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

  19. Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

    Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 x 106 of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

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

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

    2012-01-01

    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...

  1. 重组人骨形态发生蛋白2调节人脂肪间充质干细胞表达血管内皮生长因子***★%Recombinant human bone morphogenetic protein-2 adjusts expression of vascular endothelial growth factor in human adipose-derived mesenchymal stem cells

    曹鑫; 金格勒; 杨毅; 陈慧锦; 殷剑

    2013-01-01

    BACKGROUND: Recombinant bone morphogenetic protein-2 can promote tissue engineering bone vascularization, but its biological rules targeting human cel s are not clear. At present, there is in which report on recombinant bone morphogenetic protein-2 adjusts the expression of vascular endothelial growth factor in human cel s. OBJECTIVE: To observe and compare the expression of vascular endothelial growth factor in human adipose-derived mesenchymal stem cel s on gene level and protein level at different time points after induced with human recombinant bone morphogenetic protein-2. METHODS: Adipose-derived mesenchymal stem cel s were separated from adult human adipose tissues and cultured until passage 3, then divided into induced group and control group. The cel s in the induced group were induced by human recombinant bone morphogenetic protein-2 which final concentration was 100 μg/L, then the samples were col ected at 3, 6, 12, 18, 24, 36 and 48 hours after induction. Reverse transcription-PCR and enzyme-linked immunosorbent assay were used to detect vascular endothelial growth factor expression on gene level and protein level, compared with the control group. RESULTS AND CONCLUSION: Human recombinant bone morphogenetic protein-2 adjusted vascular endothelial growth factor expression of adipose mesenchymal stem cel s in a time-dependent manner, and the expression of vascular endothelial growth factor changed at different time points. Compared with the control group, human recombinant bone morphogenetic protein-2 could suppress vascular endothelial growth factor expression at 3-6 hours (P < 0.05), while at 18-24 hours, human recombinant bone morphogenetic protein-2 could promote vascular endothelial growth factor expression (P < 0.05). These two time periods should be paid attention when using human recombinant bone morphogenetic protein-2 to promote tissue engineering bone vascularization.%  背景:重组人骨形态发生蛋白2可以促进组织工程骨

  2. Modulation of bone marrow stromal cell functions in infectious diseases by toll-like receptor ligands

    Nemeth, Krisztian; Mayer, Balazs; Mezey, Eva

    2009-01-01

    Bone marrow-derived stromal cells (BMSCs, or as they are frequently referred to as mesenchymal stem cells) have been long known to support hematopoiesis and to regenerate bone, cartilage, and adipose tissue. In the last decade, however, a vast amount of data surfaced in the literature to suggest new roles for these cells including tissue regeneration and immunomodulation. A great number of review articles appeared that summarize these new data and focus on different aspects of the physiology ...

  3. Effect of bone marrow stromal cells transplantation on expressions of cyclooxygenase-2 and vascular endothelial growth factor in rats following spinal cord injury%骨髓基质细胞移植对大鼠脊髓损伤后环氧化酶-2和血管内皮生长因子表达的影响

    于德水; 曹阳; 梅晰凡; 王岩松; 闫鹏; 吕刚

    2013-01-01

    目的:观察骨髓基质细胞(bone marrow stromal cells,BMSCs)移植对大鼠脊髓损伤后环氧化酶-2(cyclooxygenase-2, COX-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达的影响。方法大鼠随机分为3组:A为假手术组,B为细胞培养基(DMEM)对照组,C为BMSCs移植组。B组和C组大鼠进行脊髓压迫损伤模型制作。脊髓损伤后, B组和C组大鼠分别给予DMEM培养液或BMSCs脊髓损伤周围区注射。术后应用Western Blot方法检测COX-2、VEGF蛋白在损伤脊髓组织中的表达变化。结果 COX-2、VEGF蛋白在A组大鼠未损伤脊髓组织中均低水平表达。B组与A组相比,脊髓损伤后COX-2蛋白表达水平明显增加(P<0.01),VEGF蛋白表达水平则短暂显著增加(P<0.05)。C组与B组相比, COX-2和VEGF蛋白表达水平均显著增加。结论 BMSCs移植能够增加脊髓损伤后COX-2、VEGF蛋白的表达。%Objective To observe the effect of bone marrow stromal cells (BMSCs) transplantation on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) protein in rats following spinal cord injury (SCI). Methods Adult rats were randomly divided into group A (sham operation group), group B (DMEM control group), and group C (BMSCs transplantation group). A rat spinal cord compression injury model was established. Rats in groups B and C were injected with BMSCs or DMEM after SCI. Expression of COX-2 and VEGF protein in rats following SCI was detected by Western blot. Results The expression level of COX-2 and VEGF protein was low in group A. The expression level of COX-2 and VEGF protein was significantly higher in group B than in group A and in group C than in group B (P<0.01, P<0.05). Conclusion BMSCs transplantation can up-regulate the expression of COX-2 and VEGF protein in rats following SCI.

  4. Defective pericyte recruitment of villous stromal vessels as the possible etiologic cause of hydropic change in complete hydatidiform mole.

    Kyu Rae Kim

    Full Text Available The pathogenetic mechanism underlying the hydropic change in complete hydatidiform moles (CHMs is poorly understood. A growing body of data suggests that pericytes play a role in vascular maturation. Since maturation of villous stromal vessels in CHMs is markedly impaired at early stages, we postulated that a defect in pericytes around stromal vessels in chorionic villi might cause vascular immaturity and subsequent hydropic change. To investigate this, we examined several markers of pericytes, namely, α-smooth muscle actin (α-SMA, platelet-derived growth factor receptor-β (PDGFR-β, and desmin, in 61 normally developing placentas and 41 CHMs with gestational ages of 4-12 weeks. The ultrastructure of villous stromal vessels was also examined. Mature blood vessels from normal placentas show patent vascular lumens and formed hematopoietic components in the villous stroma. α-SMA and PDGFR-β expression in the villous stroma gradually increased and extended from the chorionic plate to peripheral villous branches. The labeled cells formed a reticular network in the villous stroma and, after week 7, encircled villous stromal vessels. In comparison, α-SMA and PDGFR-β expression in the villous stroma and stromal vessels of CHMs was significantly lower (p<0.05. Ultrastructurally, endothelial cells in villous stromal vessels in normal placentas were consistently attached by pericytes after week 7 when the vessels formed distinct lumen, whereas the villous stromal vessels in CHMs consisted of linear chains of endothelial cells, often disclosing primitive clefts without hematopoietic cells inside, and neither pericytes nor basal lamina surrounded the endothelial cells at any gestational age studied. This suggests that pericytes recruitment around villous stromal vessels is defective in CHMs and links to the persistent vascular immaturity of the villous stroma in CHMs, which in turns leads to hydropic villi.

  5. Telomere length differences between subcutaneous and visceral adipose tissue in humans

    Lakowa, Nicole; Trieu, Nhu; Flehmig, Gesine [Department of Medicine, University of Leipzig, Leipzig (Germany); Lohmann, Tobias [Municipal Clinic Dresden-Neustadt, Dresden (Germany); Schön, Michael R. [Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe (Germany); Dietrich, Arne [Department of Surgery, University of Leipzig, Leipzig (Germany); IFB AdiposityDiseases, University of Leipzig, Leipzig (Germany); Zeplin, Philip Helge; Langer, Stefan [Department of Orthopaedics, Traumatology and Plastic Surgery, University of Leipzig, Leipzig (Germany); Stumvoll, Michael; Blüher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Klöting, Nora, E-mail: nora.kloeting@medizin.uni-leipzig.de [IFB AdiposityDiseases, Junior Research Group 2 “Animal Models of Obesity”, University of Leipzig, Leipzig (Germany)

    2015-02-13

    Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = −0.205, P < 0.05) and independently of age with HbA1c (r = −0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. - Highlights: • Telomere lengths (TL) differ between fat depots mainly due to different lengths in SVF. • TL is not associated with gender, BMI and T2D. • The tendency for

  6. Telomere length differences between subcutaneous and visceral adipose tissue in humans

    Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = −0.205, P < 0.05) and independently of age with HbA1c (r = −0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. - Highlights: • Telomere lengths (TL) differ between fat depots mainly due to different lengths in SVF. • TL is not associated with gender, BMI and T2D. • The tendency for

  7. Tumor suppression by stromal TIMPs.

    Shimoda, Masayuki; Jackson, Hartland W; Khokha, Rama

    2016-05-01

    The tumor stroma has the capacity to drive cancer progression, although the mechanisms governing these effects are incompletely understood. Recently, we reported that deletion of tissue inhibitor of metalloproteinases (Timps) in fibroblasts unleashes the function of cancer-associated fibroblasts and identifies a novel mode of stromal-tumor communication that activates key oncogenic pathways invoving Notch and ras homolog gene family, member A (RhoA) via stromal exosomes. PMID:27314104

  8. Sclerosing Stromal Tumor of Ovary

    Hsiu-Huei Peng; Ting-Chang Chang; Swei Hsueh

    2003-01-01

    Sclerosing stromal tumor of the ovary is a rare ovarian disease with prevalence of 1.5%to 6% of ovarian stromal tumors. We present a 24-year-old woman with irregular menstruationfor 6 months and a self-palpable lower abdominal mass. Enucleation of the left ovariantumor was undertaken. Gross examination showed a soft elastic tumor with a smooth outersurface and diffusely white edematous stroma with scattered yellowish nodular areas on thecut surface. Histologic study showed that the cellular n...

  9. Long-Duration Three-Dimensional Spheroid Culture Promotes Angiogenic Activities of Adipose-Derived Mesenchymal Stem Cells.

    Lee, Jun Hee; Han, Yong-Seok; Lee, Sang Hun

    2016-05-01

    Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine. PMID:26869524

  10. Gastrointestinal stromal tumor

    Levidou Georgia

    2009-08-01

    Full Text Available Abstract Background GISTs are a subset of mesenchymal tumors and represent the most common mesenchymal neoplasms of GI tract. However, GIST is a recently recognized tumor entity and the literature on these stromal tumors has rapidly expanded. Methods An extensive review of the literature was carried out in both online medical journals and through Athens University Medical library. An extensive literature search for papers published up to 2009 was performed, using as key words, GIST, Cajal's cells, treatment, Imatinib, KIT, review of each study were conducted, and data were abstracted. Results GIST has recently been suggested that is originated from the multipotential mesenchymal stem cells. It is estimated that the incidence of GIST is approximately 10-20 per million people, per year. Conclusion The clinical presentation of GIST is variable but the most usual symptoms include the presence of a mass or bleeding. Surgical resection of the local disease is the mainstay therapy. However, therapeutic agents, such as Imatinib have now been approved for the treatment of advanced GISTs and others, such as everolimus, rapamycin, heat shock protein 90 and IGF are in trial stage demonstrate promising results for the management of GISTs.

  11. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

    Dietmar Abraham

    2013-09-01

    Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

  12. Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

    Tasić Desanka

    2004-01-01

    Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

  13. Adipose Mesenchymal Stem Cells Isolated after Manual or Water-jet-Assisted Liposuction Display Similar Properties

    Bony, Claire; Cren, Mailys; Domergue, Sophie; Toupet, Karine; Jorgensen, Christian; Noël, Danièle

    2016-01-01

    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 past years, a number of devices for fat liposuction intended for clinical use have been commercialized but few papers have compared these procedure...

  14. The Therapeutic Effect of Human Adult Stem Cells Derived from Adipose Tissue in Endotoxemic Rat Model

    Soyoung Shin, Yonggoo Kim, Sikyoung Jeong, Sungyoup Hong, Insoo Kim, Woonjeong Lee, Seungphil Choi

    2013-01-01

    Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs), commonly referred to as mesenchymal stem cells (MSCs), has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs), which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. ...

  15. The Therapeutic Effect of Human Adult Stem Cells Derived from Adipose Tissue in Endotoxemic Rat Model

    Shin, Soyoung; Kim, Yonggoo; Jeong, Sikyoung; Hong, Sungyoup; Kim, Insoo; Lee, Woonjeong; Choi, Seungphil

    2012-01-01

    Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs), commonly referred to as mesenchymal stem cells (MSCs), has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs), which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. ...

  16. Glioblastoma Therapy with Cytotoxic Mesenchymal Stromal Cells Optimized by Bioluminescence Imaging of Tumor and Therapeutic Cell Response

    Maria Alieva; Bagó, Juli R.; Elisabet Aguilar; Carolina Soler-Botija; Vila, Olaia F.; Joan Molet; Gambhir, Sanjiv S.; Nuria Rubio; Jerónimo Blanco

    2012-01-01

    Genetically modified adipose tissue derived mesenchymal stromal cells (hAMSCs) with tumor homing capacity have been proposed for localized therapy of chemo- and radiotherapy resistant glioblastomas. We demonstrate an effective procedure to optimize glioblastoma therapy based on the use of genetically modified hAMSCs and in vivo non invasive monitoring of tumor and therapeutic cells. Glioblastoma U87 cells expressing Photinus pyralis luciferase (Pluc) were implanted in combination with hAMSCs ...

  17. Influence of microbial products and inflammation on the function of mesenchymal stromal cells isolated from different sources

    Raicevic, Gordana

    2011-01-01

    Mesenchymal stromal cells (MSC) are adherent, clonogenic, fibroblast-like cells endowing with unique multipotent differentiation potential and immunosuppressive properties. They are considered as promising candidates for regenerative medicine and immunotherapy. MSC can be isolated from different tissue sources including bone marrow (BM), adipose tissue (AT) and Wharton’s Jelly (WJ). Although fulfilling the ISCT criteria required to be recognized as MSC, MSC from these different sources could ...

  18. Adipose Tissue Metabolism During Hypobaria

    D. P. Chattopadhyay

    1974-10-01

    Full Text Available Possible factors affecting the metabolism of adipose tissue under hypobaric conditions have been reviewed. The hormonal changes brought into play under hypoxic stress generally stress generally increase the adipose tissue lipolysis.

  19. Vascular Stiffness in Insulin Resistance and Obesity

    Guanghong eJia

    2015-08-01

    Full Text Available Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

  20. Bone marrow stromal elements in murine leukemia

    A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL-1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNFα in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicity, reduced CSF production. (author)

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

    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

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

    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

  3. Contribution of INTRAMUSCULAR Autologous Adipose Tissue-Derived Stem Cell Injections to Treat Cutaneous Radiation Syndrome: Preliminary Results.

    Riccobono, Diane; Agay, Diane; François, Sabine; Scherthan, Harry; Drouet, Michel; Forcheron, Fabien

    2016-08-01

    Cutaneous radiation syndrome caused by high dose located irradiation is characterized by delayed symptoms, incomplete wound healing, and poor revascularization. Subcutaneous adipose tissue derived stromal/stem cells have been shown to improve skin repair in a minipig model of cutaneous radiation syndrome despite a subcutaneous defect being a consequence of radio-induced muscular fibrosis. Based on the pro-myogenic potential of stromal/stem cells, a new protocol combining subcutaneous and intramuscular injections was evaluated in a preliminary study. Six female minipigs were locally irradiated at the dose of 50 Gy using a Co source (0.6 Gy min) and randomly divided into two groups. Three animals received the vehicle (phosphate-buffer-saline solution) and three animals received three injections of 75 × 10 adipose tissue derived stromal/stem cells each time (day 25, 46, and 66 post-irradiation). Pigs were euthanized on day 76 post-irradiation before development of clinical skin symptoms. All minipigs exhibited a homogeneous skin evolution. Macroscopic observation of irradiated muscles showed prominent fibrosis and necrosis areas in controls as opposed to adipose tissue-derived stromal/stem cells injected animals. Moreover, muscle biopsy analysis highlighted a recruitment of myofibroblasts (Immune Reactive Score: p work is ongoing to evaluate this therapeutic strategy on a larger animal number with a longer clinical follow-up. PMID:27356055

  4. Bisphenol A Promotes Adiposity and Inflammation in a Nonmonotonic Dose-response Way in 5-week-old Male and Female C57BL/6J Mice Fed a Low-calorie Diet.

    Yang, Minglan; Chen, Maopei; Wang, Jiqiu; Xu, Min; Sun, Jichao; Ding, Lin; Lv, Xiaofei; Ma, Qinyun; Bi, Yufang; Liu, Ruixin; Hong, Jie; Ning, Guang

    2016-06-01

    A growing body of epidemiological research show that Bisphenol A (BPA) is positively correlated with obesity and metabolic disorders. However, the mechanisms of BPA on adiposity remain largely unknown. In this study, we found that 5-week-old male and female C57BL/6J mice exposed to four dosages of BPA (5, 50, 500, and 5000 μg/kg/d) by oral intake for 30 days showed significantly increased body weight and fat mass in a nonmonotonic dose-dependent manner when fed a chow diet. The effect occurred even at the lowest concentration (5μg/kg/d), lower than the tolerable daily intake of 50 μg/kg/day for BPA. However, no significant difference in body weight and fat mass was observed in either male or female mice fed a high-fat diet, suggesting that BPA may interact with diet in promoting obesity risk. In vitro study showed that BPA treatment drives the differentiation of white adipocyte progenitors from the stromal vascular fraction, partially through glucocorticoid receptor. BPA exposure increased circulating inflammatory factors and the local inflammation in white adipose tissues in both genders fed a chow diet, but not under high-fat diet. We further found that BPA concentration was associated with increased circulating inflammatory factors, including leptin and TNFα, in lean female subjects (body mass index 25.0 kg/m(2)). In conclusion, we demonstrated the nonmonotonic dose effects of BPA on adiposity and chronic inflammation in 5-week-old mice, which is related to caloric uptake. PMID:27145005

  5. Role of Vascular Endothelial Growth Factor Signaling in Brown Adipocyte Survival, Proliferation and Function

    Bagchi, Mandrita

    2012-01-01

    Both white and brown adipose tissues exhibit extensive vascularity. Increased angiogenesis in brown adipose tissue (BAT) is crucial for brown fat activation and thermogenesis in animals during cold acclimation. BAT can be similarly activated by food intake to generate heat through cellular respiration, in a process known as diet induced thermogenesis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that regulates both pathological and physiological angiogenesis and can...

  6. 不同细胞促进脂肪移植存活的实验研究%Effects of different human adipose-derived cells in promoting human adipose tissue engraftment in nude mice

    朱茗; 鲁峰; 高建华; 廖云君

    2012-01-01

    目的 探讨应用自人脂肪组织来源的不同细胞辅助脂肪移植,寻找促进移植物存活率的最佳种子细胞的有效方法,为干细胞进一步运用于临床提供实验依据.方法 从临床抽脂病人获取脂肪组织并提炼细胞,将0.3 ml待移植的脂肪颗粒分别与以下细胞进行混合处理:(1)低氧脂肪来源间充质干细胞(A组);(2)脂肪来源间充质干细胞(B组);(3)血管基质层细胞(SVFs)(C组);(4)加完全培养基的单纯脂肪颗粒为对照组(D组)脂肪颗粒与相应细胞混合后,注射移植于6只裸鼠背部皮下.术后3个月观察移植物情况,通过组织学、HE染色等方法进行分析.结果 A~D组湿重分别为(61.67±8.165)、(91.67±1.472)、(96.67±5.164)和(40.83±4.916)mg,A、B、C组脂肪存活率均高于D组(P<0.05),B、C两组之间比较差异无统计学意义(P>0.05)且都高于A组.A、B、C组血管密度均高于组D,且C组明显高于其他3组(P<0.05).A、B、C组存活脂肪细胞计数均高于D组,且B、C组最高(P<0.05),纤维组织计数均低于D组(P<0.05).结论 来源于人自体干细胞复合脂肪颗粒能够显著提高移植脂肪组织的成活率,其中血管基质层细胞及脂肪来源间充质干细胞移植脂肪的存活率最高.%Objective To explore the optimal seed cells derived from human adipose tissue for promoting the engraftment of transplanted adipose tissue in nude mice. Methods Human adipose tissue granules (0.3 ml) obtained from patients undergoing liposuction were mixed with hypoxic adipose-derived stem cells (ADCs, group A), ADCs (Group B), stromal vascular fraction (SVF) cells (group C), or pure adipose tissue granules in complete culture medium particles (group D). The mixtures were injected subcutaneously on the back of 6 nude mice, and the transplanted adipose tissues were harvested 3 months later to examine the engraftment using histological method and HE staining. Results The wet weights of the adipose

  7. Exercise protects against obesity-induced endothelial dysfunction via promoting perivascular adipose tissue browning

    Zhong, Cheng

    2015-01-01

    Overweight and obesity have reached epidemics worldwide. Obesity represents the independent risk factor for a serious of diseases including cardiovascular diseases. Exercise is one of the most efficient ways to prevent or delay the onset of cardiovascular diseases. But the detailed mechanism is still poorly understood. Perivascular adipose tissue (PVAT) is the adipose tissue surrounding the blood vessels. Emerging evidence has shown that PVAT plays an active role in modulating vascular functi...

  8. Gastrointestinal stromal tumors: CT and MRI findings

    Sandrasegaran, Kumaresan; Rydberg, Jonas; Akisik, Fatih M. [Indiana University Medical Center, Department of Radiology, Indianapolis, IN (United States); Rajesh, Arumugam [United Leicester Hospitals, Department of Radiology, Leicester (United Kingdom); Rushing, Daniel A. [Indiana University Medical Center, Department of Oncology, Indianapolis, Indiana (United States); Henley, John D. [Indiana University Medical Center, Department of Pathology, Indianapolis, Indiana (United States)

    2005-07-01

    The objective of this study was to report the CT and MRI appearances of primary and metastatic gastrointestinal stromal tumor (GIST). The clinical and imaging findings of 31 patients with histological and immunohistochemical diagnosis of GIST were reviewed. The CT and MRI findings were assessed independently for size, location, enhancement characteristics, and pattern of metastatic disease. The tumors were of enteric (n=13), gastric (n=12), duodenal (n=2), and rectal (n=3) origin. In one case the primary site was the mesentery, without involvement of bowel. Primary tumors were typically exophytic (79%), larger than 5 cm (84%), and inhomogeneously enhancing (84%). Central necrosis of all tumors (37%) and aneurysmal dilation of enteric tumors (33%) were less common. Metastases were most commonly to mesentery (26%) or liver (32%). Less common findings were ascites (7%) and omental caking (3%). Liver metastases were hypervascular in 92% of patients and rapidly became cystic following therapy with imatinib mesylate (Gleevec; Novartis, East Hanover, NJ, USA). Lung metastases, bowel obstruction, vascular invasion, and significant lymphadenopathy were not seen in any patient. GISTs have some specific CT findings which could help differentiate them from other gastrointestinal tumors. Liver metastases became cystic following therapy, mimicking simple cysts. MRI was better than single-phase CT for assessing liver metastases, while CT was more sensitive for mesenteric metastases. (orig.)

  9. Stem cells transplanted with vascular endothelial growth factor 165 gene for improving the survival of tissue-engineered adipose%血管内皮细胞生长因子165基因转染干细胞促进组织工程化脂肪的存活

    杨波; 沈宏亮; 徐志飞; 陈坤; 李嵩

    2012-01-01

    背景:体外构建工程组织时常因植入区血供不良或植入物建立血管化过程延长,造成种子细胞缺乏营养,代谢紊乱,增殖、分化及分泌功能受损甚至死亡,移植物最终失效.目的:观察血管内皮细胞生长因子165基因转染脂肪组织来源干细胞移植能否促进组织工程脂肪组织的血管新生.方法:利用腺病毒介导血管内皮细胞生长因子165基因体外转染人脂肪来源干细胞,然后与脂肪组织工程移植物混合移植于裸鼠背部(实验组),以移植脂肪来源干细胞+脂肪组织工程移植物(细胞组)、DMEM培养基+脂肪组织工程移植物(对照组)为对照.结果与结论:移植后3个月,实验组脂肪组织存活湿质量、脂肪组织血管密度高于细胞组与对照组(P < 0.01,P < 0.05),且细胞组均高于对照组.说明脂肪来源干细胞可促进组织工程脂肪组织的血管新生,提高存活水平,转染血管内皮细胞生长因子165基因后具有更强的促血管新生的作用.%BACKGROUND: During in vitro tissue engineering construction, poor blood supply in transplanted areas or delayedrevascularization of implants leads to nutrition deficiency of seed cells, metabolism disorders, proliferation, differentiation andsecretion dysfunction or even death, and at last causes the transplantation failure.OBJECTIVE: To investigate the feasibility of transfecting vascular endothelial growth factor 165 (VEGF165) gene into humanadipose tissue-derived stem cells (ADSCs) for the neovascularization of tissue engineered adipose.METHODS: ADSCs were transfected by adenovirus-mediated VEGF165 gene, and transfected ADSCs combined with collagensponge were transplanted into the back of nude mice as experimental group. Non-transfected ADSCs with collagen sponge wasused as cell group, and DMEM culture medium+collagen sponge as control group.RESULTS AND CONCLUSION: Three months after transplantation, survival volume and capillary density of adipose

  10. Mechanosensation in an adipose fin.

    Aiello, Brett R; Stewart, Thomas A; Hale, Melina E

    2016-03-16

    Adipose fins are found on approximately 20% of ray-finned fish species. The apparently rudimentary anatomy of adipose fins inspired a longstanding hypothesis that these fins are vestigial and lack function. However, adipose fins have evolved repeatedly within Teleostei, suggesting adaptive function. Recently, adipose fins were proposed to function as mechanosensors, detecting fluid flow anterior to the caudal fin. Here we test the hypothesis that adipose fins are mechanosensitive in the catfish Corydoras aeneus. Neural activity, recorded from nerves that innervate the fin, was shown to encode information on both movement and position of the fin membrane, including the magnitude of fin membrane displacement. Thus, the adipose fin of C. aeneus is mechanosensitive and has the capacity to function as a 'precaudal flow sensor'. These data force re-evaluation of adipose fin clipping, a common strategy for tagging fishes, and inform hypotheses of how function evolves in novel vertebrate appendages. PMID:26984621

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

    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.

  12. High Risk of Metabolic and Adipose Tissue Dysfunctions in Adult Male Progeny, Due to Prenatal and Adulthood Malnutrition Induced by Fructose Rich Diet.

    Alzamendi, Ana; Zubiría, Guillermina; Moreno, Griselda; Portales, Andrea; Spinedi, Eduardo; Giovambattista, Andrés

    2016-03-01

    The aim of this work was to determine the effect of a fructose rich diet (FRD) consumed by the pregnant mother on the endocrine-metabolic and in vivo and in vitro adipose tissue (AT) functions of the male offspring in adulthood. At 60 days of age, rats born to FRD-fed mothers (F) showed impaired glucose tolerance after glucose overload and high circulating levels of leptin (LEP). Despite the diminished mass of retroperitoneal AT, this tissue was characterized by enhanced LEP gene expression, and hypertrophic adipocytes secreting in vitro larger amounts of LEP. Analyses of stromal vascular fraction composition by flow cytometry revealed a reduced number of adipocyte precursor cells. Additionally, 60 day-old control (C) and F male rats were subjected to control diet (CC and FC animals) or FRD (CF and FF rats) for three weeks. FF animals were heavier and consumed more calories. Their metabolic-endocrine parameters were aggravated; they developed severe hyperglycemia, hypertriglyceridemia, hyperleptinemia and augmented AT mass with hypertrophic adipocytes. Our study highlights that manipulation of maternal diet induced an offspring phenotype mainly imprinted with a severely unhealthy adipogenic process with undesirable endocrine-metabolic consequences, putting them at high risk for developing a diabetic state. PMID:27011203

  13. Pseudoangiomatous stromal hyperplasia of the breast in pediatric patients: an underrecognized entity.

    Shehata, Bahig M; Fishman, Inessa; Collings, Margaret H; Wang, Jenny; Poulik, Janet M; Ricketts, Richard R; Parker, Paul M; Heiss, Kurt; Bhatia, Amina M; Worcester, Heath D; Gow, Kenneth W

    2009-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion consisting of mammary stromal proliferation with anastomosing slits mimicking vascular spaces. Grossly, it most often resembles fibroadenoma, but may commonly be confused with angiosarcoma and other types of benign vascular proliferations. While PASH has been described in female and male adults since the mid-1980s, there have been only a few accounts in the pediatric population. We present a series of 12 pediatric patients with PASH, including a 3-year-old male, who we believe to be the youngest patient to present with this entity. In our study, PASH was found in 12% of tumors diagnosed preoperatively as fibroadenomas and in 12% of cases diagnosed preoperatively as gynecomastia. Our series documents that PASH is not uncommon in pediatric breast pathology and delineates important differences between adult and pediatric presentations of this entity. PMID:19606909

  14. Prostatic Stromal Hyperplasia with Atypia

    Hutchinson, Ryan C.; Wu, Kevin J.; Cheville, John C.; Thiel, David D

    2013-01-01

    Prostatic stromal hyperplasia with atypia (PSHA) is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and revie...

  15. Prostatic Stromal Hyperplasia with Atypia

    Ryan C. Hutchinson

    2013-01-01

    Full Text Available Prostatic stromal hyperplasia with atypia (PSHA is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and review the literature on this rare pathologic finding.

  16. Human Mesenchymal Stromal Cell-Mediated Immunoregulation: Mechanisms of Action and Clinical Applications

    Akaitz Dorronsoro

    2013-01-01

    Full Text Available Mesenchymal stromal cells (MSCs are multipotent cells found in connective tissues that can differentiate into bone, cartilage, and adipose tissue. Interestingly, they can regulate immune responses in a paracrine way and allogeneic MSCs do not elicit immune response. These properties have encouraged a number of clinical trials in a broad range of regenerative therapies. Although these trials were first focused on their differentiation properties, in the last years, the immunosuppressive features have gained most of the attention. In this review, we will summarize the up-to-date knowledge about the immunosuppressive mechanisms of MSCs in vivo and in vitro and the most promising approaches in clinical investigation.

  17. Vascular MR

    This project investigates cardiac gated gradient echo pulses sequences for vascular MR imaging. These pulse sequences have been used to acquire and display MR projection angiograms. The authors have applied these methods in two distinct populations of patients for evaluation and comparison with standard angiography. Twenty patients with abdominal aortic aneurysms, and 35 patients with aortoiliac atherosclerotic disease or peripheral vascular disease were investigated using this method and the results are presented

  18. Vascular Dementia

    Maria Alekseyevna Cherdak; O. V. Uspenskaya

    2015-01-01

    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment ...

  19. Pseudoangiomatous stromal hyperplasia: an overview.

    Virk, Renu K; Khan, Ashraf

    2010-07-01

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign, proliferative mesenchymal lesion with possible hormonal etiology. It typically affects women in the reproductive age group. Pseudoangiomatous stromal hyperplasia is frequently an incidental histologic finding in breast biopsies performed for other benign or malignant lesions. Rarely, it can present as a firm, painless breast mass, which has been referred to as nodular or tumorous PASH. Grossly, tumorous PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slitlike spaces in dense collagenous stroma. The spaces are lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. The most important differential diagnosis on histopathology is angiosarcoma. Pseudoangiomatous stromal hyperplasia discovered incidentally does not require any additional specific treatment. Tumorous PASH is treated by local surgical excision with clear margins and the prognosis is excellent, with minimal risk of recurrence after adequate surgical excision. PMID:20586640

  20. Bovine endometrial stromal cells display osteogenic properties

    Cavirani Sandro

    2008-12-01

    Full Text Available Abstract The endometrium is central to mammalian fertility. The endometrial stromal cells are very dynamic, growing and differentiating throughout the estrous cycle and pregnancy. In humans, stromal cells appear to have progenitor or stem cell capabilities and the cells can even differentiate into bone. It is not clear whether bovine endometrial stromal cells exhibit a similar phenotypic plasticity. So, the present study tested the hypothesis that bovine endometrial stromal cells could be differentiated along an osteogenic lineage. Pure populations of bovine stromal cells were isolated from the endometrium. The endometrial stromal cell phenotype was confirmed by morphology, prostaglandin secretion, and susceptibility to viral infection. However, cultivation of the cells in standard endometrial cell culture medium lead to a mesenchymal phenotype similar to that of bovine bone marrow cells. Furthermore, the endometrial stromal cells developed signs of osteogenesis, such as alizarin positive nodules. When the stromal cells were cultured in a specific osteogenic medium the cells rapidly developed the characteristics of mineralized bone. In conclusion, the present study has identified that stromal cells from the bovine endometrium show a capability for phenotype plasticity similar to mesenchymal progenitor cells. These observations pave the way for further investigation of the mechanisms of stroma cell differentiation in the bovine reproductive tract.

  1. Independent Stem Cell Lineages Regulate Adipose Organogenesis and Adipose Homeostasis

    Yuwei Jiang

    2014-11-01

    Full Text Available Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide a discrete therapeutic target for childhood and adult obesity.

  2. Independent Stem Cell Lineages Regulate Adipose Organogenesis and Adipose Homeostasis

    Yuwei Jiang; Daniel C. Berry; Wei Tang; Jonathan M. Graff

    2014-01-01

    Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult pr...

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

    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.

  4. Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues.

    Gabrielson, Marike; Chiesa, Flaminia; Paulsson, Janna; Strell, Carina; Behmer, Catharina; Rönnow, Katarina; Czene, Kamila; Östman, Arne; Hall, Per

    2016-07-01

    Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012-2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement

  5. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue.

    Šram, Miroslav; Vrselja, Zvonimir; Lekšan, Igor; Ćurić, Goran; Selthofer-Relatić, Kristina; Radić, Radivoje

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. PMID:26124828

  6. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue

    Miroslav Šram

    2015-01-01

    Full Text Available Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT and visceral adipose tissue (VAT, the latter being highly associated with coronary artery disease (CAD. Expansion of epicardial adipose tissue (EAT is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1 the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2 determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.

  7. Endometrial Stromal Nodule: Report of a Case

    F. Z. Fdili Alaoui

    2011-01-01

    Full Text Available Endometrial stromal nodule (ESN is the least common of the endometrial stromal tumors. They are rare neoplasms which are diagnosed in most instances by light microscopy. Although such nodules are benign, hysterectomy has been considered the treatment of choice to determine the margins of the tumor required for diagnosis and to differentiate it from invasive stromal sarcoma Whose prognosis is totally different. We report a case of a 45 years old woman, with presurgical diagnosis of adnexal mass or uterine tumor. She underwent a total abdominal hysterectomy. Pathologic examination revealed an endometrial stromal nodule. Through this observation, we insist on the fact that the ESNs are rare and benign entities which must be differentiated from the other invasive malignant stromal tumors; this can change the final prognosis.

  8. Endometrial stromal nodule: report of a case.

    Fdili Alaoui, F Z; Chaara, H; Bouguern, H; Melhouf, M A; Fatemi, H; Belmlih, A; Amarti, A

    2011-01-01

    Endometrial stromal nodule (ESN) is the least common of the endometrial stromal tumors. They are rare neoplasms which are diagnosed in most instances by light microscopy. Although such nodules are benign, hysterectomy has been considered the treatment of choice to determine the margins of the tumor required for diagnosis and to differentiate it from invasive stromal sarcoma Whose prognosis is totally different. We report a case of a 45 years old woman, with presurgical diagnosis of adnexal mass or uterine tumor. She underwent a total abdominal hysterectomy. Pathologic examination revealed an endometrial stromal nodule. Through this observation, we insist on the fact that the ESNs are rare and benign entities which must be differentiated from the other invasive malignant stromal tumors; this can change the final prognosis. PMID:21423543

  9. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries.

    Verlohren, Stefan; Dubrovska, Galyna; Tsang, Suk-Ying; Essin, Kirill; Luft, Friedrich C; Huang, Yu; Gollasch, Maik

    2004-09-01

    Periadventitial adipose tissue produces vasoactive substances that influence vascular contraction. Earlier studies addressed this issue in aorta, a vessel that does not contribute to peripheral vascular resistance. We tested the hypothesis that periadventitial adipose tissue modulates contraction of smaller arteries more relevant to blood pressure regulation. We studied mesenteric artery rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared with vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K+-containing solutions (60 mmol/L) was similar in vessels with and without periadventitial fat. The K+ channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K+-containing solutions (60 mmol/L), suggesting that K+ channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anticontractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayed-rectifier K+ (K(v)) channels with 4-aminopyridine (2 mmol/L) or 3,4-diaminopyridine (1 mmol/L). Blocking other K+ channels with glibenclamide (3 micromol/L), apamin (1 micromol/L), iberiotoxin (100 nmol/L), tetraethylammonium ions (1 mmol/L), tetrapentylammonium ions (10 micromol/L), or Ba2+ (3 micromol/L) had no effect. Longitudinal removal of half the perivascular tissue reduced the anticontractile effect of fat by almost 50%, whereas removal of the endothelium had no effect. We suggest that visceral periadventitial adipose tissue controls mesenteric arterial tone by inducing vasorelaxation via K(v) channel activation in vascular smooth muscle cells. PMID:15302842

  10. Multicentric malignant gastrointestinal stromal tumor

    Shukla Shailaja; Singh Sanjeet; Pujani Mukta

    2009-01-01

    Malignant gastrointestinal stromal tumor (GIST) is a rare type of sarcoma that is found in the digestive system, most often in the wall of the stomach. Multiple GISTs are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST. We report here a case of a 70-year-old woman who reported pain in the abdomen, loss of appetite, and weight loss for six months. Ultrasound examination showed a small bowel mass along with multiple peritoneal deposits and a mass within th...

  11. Carotid Repair Using Autologous Adipose-Derived Endothelial Cells

    Froehlich, Harald; Gulati, Rajiv; Boilson, Barry; Witt, Tyra; Harbuzariu, Adriana; Kleppe, Laurel; Dietz, Allan B.; Lerman, Amir; Simari, Robert D.

    2009-01-01

    Background and Purpose Adipose tissue is an abundant source of endothelial cells as well as stem and progenitor cells which can develop an endothelial phenotype. It has been demonstrated that these cells have distinct angiogenic properties in vitro and in vivo. However, whether these cells have the capacity to directly improve large vessel form and function following vascular injury remains unknown. To define whether delivery of adipose-derived endothelial cells (ADECs) would improve healing of injured carotid arteries, a rabbit model of acute arterial injury was employed. Methods Autologous rabbit ADECS were generated utilizing defined culture conditions. To test the ability of ADECs to enhance carotid artery repair, cells were delivered intra-arterially following acute balloon injury. Additional delivery studies were performed following functional selection of cells prior to delivery. Results Following rabbit omental fat harvest and digestion, a proliferative, homogenous, and distinctly endothelial population of ADECs was identified. Direct delivery of autologous ADECs resulted in marked re-endothelialization 48 hours following acute vascular injury as compared to saline controls (82.2 ±26.9% vs 4.2±3.0% pADECs that were selected for their ability to take up acetylated LDL significantly improved vasoreactivity and decreased intimal formation following vascular injury. Conclusions Taken together, these data suggest that ADECs represent an autologous source of proliferative endothelial cells which demonstrate the capacity to rapidly improve re-endothelialization, improve vascular reactivity, and decrease intimal formation in a carotid artery injury model. PMID:19286583

  12. Bioengineering beige adipose tissue therapeutics

    Kevin eTharp

    2015-10-01

    Full Text Available Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of UCP1-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable brown adipose tissues for human therapeutic purposes at this time.Recent developments in bioengineering, including novel hyaluronic acid based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit WAT derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of beige adipose tissue implants and their potential for the metabolic

  13. Bioengineering Beige Adipose Tissue Therapeutics.

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  14. Rare adipose disorders (RADs) masquerading as obesity

    Karen L HERBST

    2012-01-01

    Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL),lipedema and Dercum's disease (DD) may be misdiagnosed as obesity.Lifestyle changes,such as reduced caloric intake and increased physical activity are standard care for obesity.Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs,these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs.RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL,or by primary vascular and lymphatic dysfunction in lipedema and DD.People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone.In order to improve recognition of RADs apart from obesity,the diagnostic criteria,histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies,acquired partial lipodystrophies and obesity with which they may be confused.Treatment recommendations focus on evidencebased data and include lymphatic decongestive therapy,medications and supplements that support loss of RAD SAT.Associated RAD conditions including depression,anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs.Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.

  15. Methodologies to assess paediatric adiposity.

    Horan, M

    2014-05-04

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

  16. Aspects of surgical treatment for gastro-intestinal stromal tumors

    Gastro-intestinal stromal tumors (GIST) form the commonest subgroup of soft tissue sarcomas. They arise in the muscular layer of the esophagus, stomach, small intestines and rectum. Characteristic and important for the assessment of the extent of tumors is the peripheral rim vascularization of primary tumors and metastases. Indications for resection are given for tumors larger than 2 cm in size. Locally advanced GISTs can be advantageously treated with imatinib/sunitinib as neoadjuvant and it is often possible to select a low level of resection for this size of tumor and when the rim area is not hypervascularized. Even in the metastizing stage surgical treatment can be used for elimination of resistant metastases or for removal of residual tumor tissue in an attempt to counteract secondary tumor progression. The effect of this treatment is currently being tested in a randomized phase III study. (orig.)

  17. NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation

    Sela, M; Tirza, G; Ravid, O; Volovitz, I; Solodeev, I; Friedman, O; Zipori, D; E. Gur; Krelin, Y; Shani, N

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and can be derived from different adult tissues including fat. Our repeated attempts to produce long-term proliferative cultures of rat abdominal adipose stem cells (aASCs) under normal oxygen concentration (21%) were unsuccessful. We set to examine the events controlling this cytostasis of aASCs and found that it resulted from overproduction of reactive oxygen species (ROS) that led to apoptosis. ROS overproduction in aASCs was accompanied by ...

  18. What Is Vascular Disease?

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  19. Diabetes and Vascular Disease

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  20. Vulvar vascular tumors: a clinicopathologic study of 85 patients.

    Papalas, John A; Sangueza, Omar P; Puri, Puja K; Robboy, Stanley J; Selim, Maria A

    2013-02-01

    The subepidermal hormonally sensitive tissue of the vulva is anatomically unique and may give rise to a wide variety of vascular tumors. As a consequence, classifying vulvar vascular lesions has been challenging due both to the wide variety of lesions that may be encountered and the heterogeneity in reporting across several disciplines. The purpose of this study is to present an institutional experience of vulvar vascular lesions. Overall, 85 patients were identified over a 26-year period. Vascular lesions belonging to the following classes included (n, %total) benign vascular tumors (32, 38%), dilatations of preexisting vessels (31, 36%), hyperplasia/reactive (7, 8%), tumors with significant vascular component (11, 13%), malformations (3, 4%), and malignant vascular tumors (1, 1%). Two reaction patterns based on vulvar lymphatic pathology were identified: one is a stromal dominant pattern and the other is a vascular dominant pattern. Vulvar vascular malformations and true vascular malignancies, although rare, may have associated high morbidity. To accurately classify vulvar lymphatic lesions, the pathologist must carefully consider the patient's clinical history taking into account features such as preexisting lymphedema. PMID:23348141

  1. 血管内皮生长因子转染后脂肪组织来源干细胞蛋白分泌表达及成骨活性的检测%Detection of protein secretion and expression and osteogenic activity of adipose tissue-derived stem cells after in vitro transfection of vascular endothelial growth factor

    刘兆杰; 胡永成; 张银光; 贾健

    2013-01-01

    Objective To examine vascular endothelial growth factor (VEGF) protein secretion and expression and explore the osteogenic activity of adipose tissue-derived stem cells (ADSCs) after transfection of human VEGF.Methods The ADSCs were isolated from human adipose tissue after the digestion of collagenase.After identification by flow cytometry,the ceils were cultured and passaged in nutritive medium.Gene sequence encoding human VEGF mature peptide was obtained by Trizol reagent method from human vascular tissue.Target gene VEGF was connected with bicistronic expression vector containing green fluorescent protein to form pSELECT-GFP zeo-VEGF for transfecting 2nd,3rd,4th,5th generation ADSCs mediated by liposome.The transfection results were verified under fluorescence microscope.VEGF protein secretion by transfected cells was detected by enzyme-linked immunosorbent assay (ELISA).Secondgeneration transfected ADSCs were cultured under osteogenic conditions.The supernatant levels of alkaline phosphatase (ALP) and osteocalcin (OC) were detected.Results Liposome-mediated VEGF target gene fragment could transfect ADSCs successfully.ELISA quantitative detection showed that VEGF mRNA expression levels in supematant of the transfected group was significantly higher than the control group.And there were significant differences.After osteogenic culturing,the detections of ELISA,real-time PCR and Western blot showed that the secretion of ALP and OC of VEGF transfected group was significantly higher than that of empty vector transfected and blank cell groups.And there were significant differences (P < 0.01).Conclusion After transfected by liposome-mediated VEGF target gene fragment,human ADSCs can express biologically active VEGF mRNA in vitro continuously and effectively.Directional differentiation capacity of transfected ADSCs is significantly enhanced.%目的 观察人血管内皮生长因子(VEGF)转染后的人脂肪组织来源干细胞(ADSCs)对VEGF蛋白的分泌和表达

  2. Gastrointestinal stromal tumor: acute liquefaction necrosis

    Stromal tumors, together with leiomyomas and schwannomas, constitute the sol-called mesenchymal tumors of the intestinal wall. Stromal tumors are histologically differentiated from other mesenchymal tumors in that they are derived from the interstitial cell of Cajal. These tumors can be encountered at any point throughout the entire digestive tract, by usually develop in stomach or small bowel. the clinical presentation in anemia secondary to gastrointestinal bleeding. Acute abdomen due to perforation or necrosis is rare. We present a case of jejunal stromal tumors with massive liquefaction necrosis, a circumstance that resulted in the peculiar radiological features observed. (Author) 9 refs,

  3. Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model.

    Lu, Zijing; Yuan, Yi; Gao, Jianhua; Lu, Feng

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation. PMID:26678825

  4. 高糖及糖基化终末产物对人脂肪干细胞成骨分化能力的影响%Effects of high glucose and advanced glycation end-products on osteogenic differentiation of human adipose-derived stromal cells in vitro

    李冬松; 李叔强; 蔡波; 王苹; 冯卫; 刘建国

    2011-01-01

    BACKGROUND: Bone metabolism disorder happens in diabetic environment, bone defects in which are difficult to repair. Study addressing osteogenic property of adipose-derived stroma cells (ADSCs) in diabetic environment provides theoretical basis for its application in certain environment.OBJECTIVE: To explore the effects of high glucose (HG) and advanced glycation end-products (AGEs) on osteogenic capacity of human ADSCs. METHODS: 100 mg/L AGEs and 27.5 mmol/L HG were used to simulate in vitro diabetic environment and intervened ADSCs osteogenic differentiation. The cells were divided into 4 groups, with 6 samples in each group. The expression of type Ⅰ collagen was examined by fluorescent immunofluorescence at 21 days after osteogenic induction. The number of calcification nodes was counted under contrast phase microscopy at 14, 21 and 28 days. RESULTS AND CONCLUSION: Fluorescent quantitation scan showed that the type Ⅰ collagen amount of the AGEs+HG treated group was 2.76 times lower than that of the control group. AGEs+HG reduced the number of ADSCs calcification nodes compared with the control, HG, and AGEs groups, the differences were statistical significant (P < 0.01). AGEs and HG exposure inhibit the cognate osteogenic differentiation of ADSCs, which suggest that AGEs and HG are unfavorable factors that reduce ADSCs osteogenic ability.%背景:因糖尿病条件下骨质代谢存在紊乱,对这类骨缺损的修复具有挑战性,研究糖尿病环境下脂肪干细胞的成骨特性将为其在特定环境下的应用提供理论基础.目的:观察高糖、糖基化终末产物对人脂肪干细胞成骨分化能力的影响.方法:选取27.5 mmol/L高糖、100 mg/L糖基化终末产物体外模拟糖尿病环境,干预人脂肪干细胞成骨分化;实验分为4组,每组设立6个样本.通过荧光染色检测脂肪干细胞诱导成骨21 d时的Ⅰ型胶原表达量,矿化结节染色观测各组中等量脂肪干细胞在14,21,28 d时矿化结节

  5. Development and differentiation of adipose tissue

    Ivković-Lazar Tatjana A.

    2003-01-01

    Introduction For years adipose tissue has been considered inert, serving only as a depot of energy surplus. However, there have been recent changes, undoubtedly due to advancement of methods for studying the morphology and metabolic activities of adipose tissue (microdialysis and adipose tissue catheterization). In normal-weight subjects, adipose tissue makes 10-12% with males and 15-20% with females. About 80 % of adipose tissue is located under the skin, and the rest envelops the internal o...

  6. Gastrointestinal stromal tumor (gist) of the duodenum.

    Ghazanfar, Shahriyar; Sial, Khadim S; Quraishy, M S

    2007-06-01

    This is a report of a rare gastrointestinal stromal tumor of the duodenum in a 75 years old man who presented with recurrent episodes of intestinal obstruction and melena. The patient underwent successful Whipple's procedure. PMID:17623589

  7. Echocardiographic Assessment of Epicardial Adipose Tissue - A Marker of Visceral Adiposity

    Singh, Navneet; Singh, Harleen; Khanijoun, Harleen K; Iacobellis, Gianluca

    2007-01-01

    Visceral adipose tissue predicts an unfavorable cardiovascular and metabolic risk profile in humans. Existing methods to assess visceral adipose tissue have been limited. Thus, echocardiographic assessment of epicardial adipose tissue as a marker of visceral adiposity was suggested. The technique has been shown to be a very reliable method and an excellent measure of visceral adiposity. In this article, epicardial adipose tissue’s localization on the heart, function, method of assessment and ...

  8. Regeneration of articular cartilage using adipose stem cells.

    Im, Gun-Il

    2016-07-01

    Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1830-1844, 2016. PMID:26990234

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

    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. PMID:26546479

  10. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-01-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cel...

  11. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Mirco Galiè; Paolo Farace; Cristina Nanni; Antonello Spinelli; Elena Nicolato; Federico Boschi; Paolo Magnani; Silvia Trespidi; Valentina Ambrosini; Stefano Fanti; Flavia Merigo; Francesco Osculati; Pasquina Marzola; Andrea Sbarbati

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular ...

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

    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

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

    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

  14. Bioengineering Beige Adipose Tissue Therapeutics

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiolog...

  15. Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells

    Wang, Karin; Andresen Eguiluz, Roberto C.; Wu, Fei; Seo, Bo Ri; Fischbach, Claudia; Gourdon, Delphine

    2015-01-01

    Fibronectin (Fn) forms a fibrillar network that controls cell behavior in both physiological and diseased conditions including cancer. Indeed, breast cancer-associated stromal cells not only increase the quantity of deposited Fn but also modify its conformation. However, (i) the interplay between mechanical and conformational properties of early tumor-associated Fn networks and (ii) its effect on tumor vascularization remain unclear. Here, we first used the Surface Forces Apparatus to reveal ...

  16. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  17. Adipose Flap Versus Fascial Sling for Anterior Subcutaneous Transposition of the Ulnar Nerve.

    Verveld, Caroline J; Danoff, Jonathan R; Lombardi, Joseph M; Rosenwasser, Melvin P

    2016-02-01

    Perineural scarring is a major cause of recurrent symptoms after anterior subcutaneous transposition secured with a fascial sling. Use of a vascularized adipose flap to secure the anteriorly transposed ulnar nerve can help reduce nerve adherence and may enhance nerve recovery. In the study reported here, we retrospectively reviewed the long-term outcomes of ulnar nerve anterior subcutaneous transposition secured with either an adipose flap (16 patients) or a fascial sling (17 patients). The 33 patients underwent physical examinations and completed the DASH (Disabilities of the Arm, Shoulder, and Hand) questionnaire, visual analog scales (VASs), and the Modified Bishop Rating Scale (MBRS). There were no significant differences in DASH (P = .673), VAS pain (P = .413), or VAS weakness (P = .362) scores between the adipose flap and fascial sling groups. Physical examinations revealed no significant differences in flexion-extension arc (P = .668) or supination-pronation arc (P = .226) between the operated and nonoperated extremities. Lateral pinch strength and grip strength were comparable. On the MBRS, excellent and good outcomes were reported by 62.5% and 37.5% of the adipose flap patients, respectively, and 59% and 41% of the fascial sling patients. The contribution of perineural scarring to postoperative recurrent ulnar neuropathy is well documented. We think the pedicled adipofascial flap benefits the peripheral nerve by providing a scar tissue barrier and an optimal milieu for vascular regeneration. For all patients in the present study, symptoms improved, though the adipose flap and fascial sling groups were not significantly different in their objective outcomes. Subjective results were slightly better for the adipose flap patients but not significantly so. These findings indicate that, compared with the current standard of care, adipose flaps are more efficacious in securing the anteriorly transposed nerve. PMID:26866320

  18. Gastrointestinal stromal tumours: pictorial review

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the alimentary tract. They normally involve the stomach, the small bowel, or the colon. Localisation within the oesophagus, rectum, mesentery, omentum, or retroperitoneum is less common, GISTs are immunohistochemically identified by the expression of the c-kit protein, which is not detected in other mesenchymal tumours. The role of imaging includes the detection (subjects with occult gastro-intestinal bleeding, incidental recognition, etc.), characterisation, analysis of relations between mass and gastrointestinal wall, staging, prognostic assessment (recognition of signs of malignancy and unfavourable prognosis), and follow-up during specific treatment. Owing to the frequent exophytic growth of these lesions, differentiation of these tumours from non digestive lesions of different nature is a common diagnostic problem. Imaging findings usually allow differentiation from gastrointestinal epithelial tumours but not from non-epithelial tumours, for which histological confirmation is necessary, in part to verify potential response to therapy. Smaller lesions, which are usually benign, tend to be well-defined, relatively homogeneous, and with intraluminal growth. Larger lesions normally show well-defined or ill defined margins, inhomogeneous density both on unenhanced and on contrast-enhanced scans, with combined intraluminal/extra luminal growth and a tendency to spread to surrounding structures. Internal attenuation is often necrotic or clearly fluid. Signs of high-grade GIST include liver metastasis, gastrointestinal wall infiltration, large volume, irregular surface, ill-defined margins, inhomogeneous enhancement and peritoneal spread. Recurrences usually share the appearance of the larger, primary malignant GIST

  19. Multicentric malignant gastrointestinal stromal tumor

    Malignant gastrointestinal stromal tumor (GIST) is a rare type of sarcoma that is found in the digestive system, most often in the wall of the stomach. Multiple GISTs are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST. We report here a case of a 70-year-old woman who reported pain in the abdomen, loss of appetite, and weight loss for six months. Ultrasound examination showed a small bowel mass along with multiple peritoneal deposits and a mass within the liver. Barium studies were suggestive of a neoplastic pathology of the distal ileum. A differential diagnosis of adenocarcinoma/lymphoma with metastases was entertained. Perioperative findings showed two large growths arising from the jejunum and the distal ileum, along with multiple smaller nodules on the serosal surface and adjoining mesentery of the involved bowel segments. Segmental resection of the involved portions of the intestine was performed. Histopathological features were consistent with those of multicentric malignant GIST-not otherwise specified (GIST-NOS). Follow-up examination three months after surgery showed no evidence of recurrence. (author)

  20. Multicentric malignant gastrointestinal stromal tumor.

    Shukla, Shailaja; Singh, Sanjeet K; Pujani, Mukta

    2009-01-01

    Malignant gastrointestinal stromal tumor (GIST) is a rare type of sarcoma that is found in the digestive system, most often in the wall of the stomach. Multiple GISTs are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST.We report here a case of a 70-year-old woman who reported pain in the abdomen, loss of appetite, and weight loss for six months. Ultrasound examination showed a small bowel mass along with multiple peritoneal deposits and a mass within the liver. Barium studies were suggestive of a neoplastic pathology of the distal ileum. A differential diagnosis of adenocarcinoma/lymphoma with metastases was entertained. Perioperative findings showed two large growths arising from the jejunum and the distal ileum, along with multiple smaller nodules on the serosal surface and adjoining mesentery of the involved bowel segments. Segmental resection of the involved portions of the intestine was performed. Histopathological features were consistent with those of multicentric malignant GIST-not otherwise specified (GIST-NOS). Follow-up examination three months after surgery showed no evidence of recurrence. PMID:19568556

  1. Multicentric malignant gastrointestinal stromal tumor

    Shukla Shailaja

    2009-01-01

    Full Text Available Malignant gastrointestinal stromal tumor (GIST is a rare type of sarcoma that is found in the digestive system, most often in the wall of the stomach. Multiple GISTs are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST. We report here a case of a 70-year-old woman who reported pain in the abdomen, loss of appetite, and weight loss for six months. Ultrasound examination showed a small bowel mass along with multiple peritoneal deposits and a mass within the liver. Barium studies were suggestive of a neoplastic pathology of the distal ileum. A differential diagnosis of adenocarcinoma/lymphoma with metastases was entertained. Perioperative findings showed two large growths arising from the jejunum and the distal ileum, along with multiple smaller nodules on the serosal surface and adjoining mesentery of the involved bowel segments. Segmental resection of the involved portions of the intestine was performed. Histopathological features were consistent with those of multicentric malignant GIST-not otherwise specified (GIST-NOS. Follow-up examination three months after surgery showed no evidence of recurrence.

  2. Society for Vascular Medicine

    ... and find out! Patient Information Pages from Vascular Medicine August 2016 The Vascular Laboratory More info for ... Learn more. Trending Now: Hot Topics in Vascular Medicine Video Series Fibromuscular Dysplasia (FMD) with Drs. Jeffrey ...

  3. Adipose tissues and thyroid hormones

    Maria-Jesus eObregon

    2014-12-01

    Full Text Available The maintenance of energy balance is regulated by complex homeostatic mechanisms, including those emanating from adipose tissue. The main function of the adipose tissue is to store the excess of metabolic energy in the form of fat. The energy stored as fat can be mobilized during periods of energy deprivation (hunger, fasting, diseases. The adipose tissue has also a homeostatic role regulating energy balance and functioning as endocrine organ that secretes substances that control body homeostasis. Two adipose tissues have been identified: white and brown adipose tissues (WAT and BAT with different phenotype, function and regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and white adipocytes have different ontogenetic origin and lineage and specific markers of WAT and BAT have been identified. Brite or beige adipose tissue has been identified in WAT with some properties of BAT. Thyroid hormones exert pleiotropic actions, regulating the differentiation process in many tissues including the adipose tissue. Adipogenesis gives raise to mature adipocytes and is regulated by several transcription factors (c/EBPs, PPARs that coordinately activate specific genes, resulting in the adipocyte phenotype. T3 regulates several genes involved in lipid mobilization and storage and in thermogenesis. Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial function, transcription factors, the availability of nutrients. T3 acts directly through specific TREs in the gene promoters, regulating transcription factors. The deiodinases D3, D2 and D1 regulate the availability of T3. D3 is activated during proliferation, while D2 is linked to the adipocyte differentiation program, providing T3 needed for lipogenesis and thermogenesis. We examine the differences between BAT, WAT and brite/beige adipocytes and the process that activate UCP1 in WAT and

  4. What Are the Risk Factors for Gastrointestinal Stromal Tumors?

    ... what causes gastrointestinal stromal tumors? What are the risk factors for gastrointestinal stromal tumors? A risk factor is ... disease like cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like ...

  5. What Should You Ask Your Doctor about Gastrointestinal Stromal Tumors?

    ... treatment for gastrointestinal stromal tumors? What should you ask your doctor about gastrointestinal stromal tumors? As you ... cancer care team. You should feel free to ask any question that’s on your mind, no matter ...

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

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

    2013-01-01

    Repair of soft-tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft-tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM, incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were p...

  7. Lipolysis in human adipose tissue during exercise

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

    2002-01-01

    adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest and...

  8. Uterine endometrial stromal sarcoma with rhabdoid and smooth muscle differentiation.

    Kim, Y.H.(Center for Underground Physics, Institute for Basic Science (IBS), Daejon, 305-811, Korea); Cho, H; Kyeom-Kim, H.; Kim, I

    1996-01-01

    Uterine and extrauterine tumors composed of cells featuring endometrial stromal cells often show ovarian sex cord-like structures and smooth muscle differentiation. A few cases of endometrial stromal tumors showing rhabdoid differentiation have been reported. The present case is a 20-year-old woman with endometrial stromal sarcoma that had sex cord-like structures, smooth muscle components and rhabdoid differentiation.

  9. Vibrational and structural investigations on adipose tissues

    Giarola, Marco; Guella, G.; Mariotto, G.; Monti, Francesca; Rossi, Barbara; Sanson, Andrea; Sbarbati, Andrea

    2008-01-01

    Abstract Two types of adipose tissue are found in mammals, including humans: the white adipose tissue (WAT) and the brown adipose tissue (BAT). The WAT has a major role in lipid storage and body thermal insulation, while the BAT is a thermogenic tissue that produces heat by oxidizing fatty acids. Both structural characterization and spectroscopic discrimination of these different adipose tissues are matter of current interest, also in view of possible medical and ...

  10. Adiposity, type 2 diabetes and Alzheimer's disease

    Luchsinger, José A.; Gustafson, Deborah R

    2009-01-01

    This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies ha...

  11. Stromal control of chronic lymphocytic leukemia cells

    Seke Etet PF

    2013-09-01

    Full Text Available Paul Faustin Seke Etet,1 Armel Herve Nwabo Kamdje,2 Jeremie Mbo Amvene,2 Yousef Aldebasi,3 Mohammed Farahna,1 Lorella Vecchio41Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Medicine, University of Ngaoundere, Ngaoundere, Cameroon; 3Department of Optometry, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 4Laboratory of Cytometry, Institute of Molecular Genetics, CNR, University of Pavia, Pavia, ItalyAbstract: In the ongoing efforts to develop therapies against chronic lymphocytic leukemia (CLL, stromal factors allowing malignant cells to escape spontaneous and chemotherapy-mediated apoptosis, giving way to relapses, have been abundantly investigated. Bone marrow adherent cell types, collectively referred to as stromal cells, appear to be key players in such escape, mainly because CLL malignant cells, which rapidly undergo spontaneous apoptosis when cultured in vitro, survive, migrate, and resist cytotoxic agents in co-culture with bone marrow stromal cells. CLL displays variable clinical courses according to well-defined prognostic factors induced on malignant B-cells (CLL cells or expressed by the transformed bone marrow stromal microenvironment. Particularly, a critical pathogenic role is played by proinflammatory factors, adhesion molecules, and signaling molecules involved in cell fate and stemness, such as Notch, Wnt, sonic Hedgehog, phosphoinositide 3-kinase (PI3K, protein kinase B (Akt, and the B-cell CLL/lymphoma 2 (Bcl-2 family of regulator proteins. As herein discussed, these molecules probably form a complex network favoring CLL cell survival, proliferation, and chemoresistance to anticancer therapy. Characterizing the sets of signaling pathways involved in the interactions between stromal cells and CLL cells may provide new tools for CLL clinical phenotyping and for re-sensitizing chemotherapy resistant cells

  12. Characterization of In Vitro Engineered Human Adipose Tissues: Relevant Adipokine Secretion and Impact of TNF-α.

    Kim Aubin

    Full Text Available Representative modelling of human adipose tissue functions is central to metabolic research. Tridimensional models able to recreate human adipogenesis in a physiological tissue-like context in vitro are still scarce. We describe the engineering of white adipose tissues reconstructed from their cultured adipose-derived stromal precursor cells. We hypothesize that these reconstructed tissues can recapitulate key functions of AT under basal and pro-inflammatory conditions. These tissues, featuring human adipocytes surrounded by stroma, were stable and metabolically active in long-term cultures (at least 11 weeks. Secretion of major adipokines and growth factors by the reconstructed tissues was determined and compared to media conditioned by human native fat explants. Interestingly, the secretory profiles of the reconstructed adipose tissues indicated an abundant production of leptin, PAI-1 and angiopoietin-1 proteins, while higher HGF levels were detected for the human fat explants. We next demonstrated the responsiveness of the tissues to the pro-inflammatory stimulus TNF-α, as reflected by modulation of MCP-1, NGF and HGF secretion, while VEGF and leptin protein expression did not vary. TNF-α exposure induced changes in gene expression for adipocyte metabolism-associated mRNAs such as SLC2A4, FASN and LIPE, as well as for genes implicated in NF-κB activation. Finally, this model was customized to feature adipocytes representative of progressive stages of differentiation, thereby allowing investigations using newly differentiated or more mature adipocytes. In conclusion, we produced tridimensional tissues engineered in vitro that are able to recapitulate key characteristics of subcutaneous white adipose tissue. These tissues are produced from human cells and their neo-synthesized matrix elements without exogenous or synthetic biomaterials. Therefore, they represent unique tools to investigate the effects of pharmacologically active products on

  13. Adipose-Derived Stem Cells

    Toyserkani, Navid Mohamadpour; Quaade, Marlene Louise; Sheikh, Søren Paludan;

    2015-01-01

    Emerging evidence has shown that adipose tissue is the richest and most accessible source of mesenchymal stem cells. Many different therapies for chronic wounds exist with varying success rates. The capacity of adipose-derived stem cells (ASCs) to promote angiogenesis, secrete growth factors......, regulate the inflammatory process, and differentiate into multiple cell types makes them a potential ideal therapy for chronic wounds. The aim of this article was to review all preclinical trials using ASCs in problem wound models. A systematic search was performed and 12 studies were found where different...

  14. Loss of stromal JUNB does not affect tumor growth and angiogenesis.

    Braun, Jennifer; Strittmatter, Karin; Nübel, Tobias; Komljenovic, Dorde; Sator-Schmitt, Melanie; Bäuerle, Tobias; Angel, Peter; Schorpp-Kistner, Marina

    2014-03-15

    The transcription factor AP-1 subunit JUNB has been shown to play a pivotal role in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well as the transcriptional regulator Cbfb and its target Mmp13. In line with these findings, it has been demonstrated that tumor cell-derived JUNB promotes tumor growth and angiogenesis. In contrast to JUNB's function in tumor cells, the role of host-derived stromal JUNB has not been elucidated so far. Here, we show that ablation of Junb in stromal cells including endothelial cells (ECs), vascular smooth muscle cells (SMCs) and fibroblasts does not affect tumor growth in two different syngeneic mouse models, the B16-F1 melanoma and the Lewis lung carcinoma model. In-depth analyses of the tumors revealed that tumor angiogenesis remains unaffected as assessed by measurements of the microvascular density and relative blood volume in the tumor. Furthermore, we could show that the maturation status of the tumor vasculature, analyzed by the SMC marker expression, α-smooth muscle actin and Desmin, as well as the attachment of pericytes to the endothelium, is not changed upon ablation of Junb. Taken together, these results indicate that the pro-angiogenic functions of stromal JUNB are well compensated with regard to tumor angiogenesis and tumor growth. PMID:24027048

  15. Vascular rarefaction mediates whitening of brown fat in obesity

    Shimizu, Ippei; Aprahamian, Tamar; Kikuchi, Ryosuke; Shimizu, Ayako; Papanicolaou, Kyriakos N.; MacLauchlan, Susan; Maruyama, Sonomi; Walsh, Kenneth

    2014-01-01

    Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet ...

  16. Association between Risk Factors for Vascular Dementia and Adiponectin

    Juhyun Song; Won Taek Lee; Kyung Ah Park; Jong Eun Lee

    2014-01-01

    Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antia...

  17. Origin of hemopoietic stromal progenitor cells in chimeras

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  18. Spontaneous hypertension occurs with adipose tissue dysfunction in perilipin-1 null mice.

    Zou, Liangqiang; Wang, Weiyi; Liu, Shangxin; Zhao, Xiaojing; Lyv, Ying; Du, Congkuo; Su, Xueying; Geng, Bin; Xu, Guoheng

    2016-02-01

    Perilipin-1 (Plin1) coats lipid droplets exclusively in adipocytes and regulates two principle functions of adipose tissue, triglyceride storage and hydrolysis, which are disrupted upon Plin1 deficiency. In the present study, we investigated the alterations in systemic metabolites and hormones, vascular function and adipose function in spontaneous hypertensive mice lacking perilipin-1 (Plin1-/-). Plin1-/- mice developed spontaneous hypertension without obvious alterations in systemic metabolites and hormones. Plin1 expressed only in adipose cells but not in vascular cells, so its ablation would have no direct effect in situ on blood vessels. Instead, Plin1-/- mice showed dysfunctions of perivascular adipose tissue (PVAT), a fat depot that anatomically surrounds systemic arteries and has an anticontractile effect. In Plin1-/- mice, aortic and mesenteric PVAT were reduced in mass and adipocyte derived relaxing factor secretion, but increased in basal lipolysis, angiotensin II secretion, macrophage infiltration and oxidative stress. Such multiple culprits impaired the anticontractile effect of PVAT to promote vasoconstriction of aortic and mesenteric arteries of Plin1-/- mice. Furthermore, arterial vessels of Plin1-/- mice showed increasing angiotensin II receptor type 1, monocyte chemotactic protein-1 and interlukin-6 expression, structural damage of endothelial and smooth muscle cells, along with impaired endothelium-dependent relaxation. Hypertension in Plin1-/- mice might occur as a deleterious consequence of PVAT dysfunction. This finding provides the direct evidence that links dysfunctional PVAT to vascular dysfunction and hypertension, particularly in pathophysiological states. This hypertensive mouse model might mimic and explain the hypertension occurring in patients with adipose tissue dysfunction, particularly with Plin1 mutations. PMID:26521150

  19. Cryopreservation and revival of mesenchymal stromal cells

    Haack-Sørensen, Mandana; Kastrup, Jens

    2011-01-01

    initiated. As there has been a precedent for the use of bone marrow stem cells in the treatment of hematological malignancies and ischemic heart diseases through randomized clinical safety and efficacy trials, the development of new therapies based on culture-expanded human mesenchymal stromal cells (MSCs...

  20. Gastrointestinal stromal tumor and mitosis, pay attention

    Federico Coccolini; Fausto Catena; Luca Ansaloni; Antonio Daniele Pinna

    2012-01-01

    The difference between stages I and III of gastric gastrointestinal stromal tumor depends principally on the number of mitosis. According with TNM classification, the presence in the tumor of high mitotic rate determines the upgrading. Many studies exposed different count techniques in evaluating the number of mitosis. An international standardized method to assess mitotic rate is needed.

  1. Prostatic stromal sarcoma with neuroectodermal differentiation

    Yamazaki Hitoshi

    2012-12-01

    Full Text Available Abstract Prostatic stromal sarcoma is a fairly rare tumor that constitutes approximately 0.1–0.2% of all prostatic cancers. Detailed characteristics of the tumor are still unclear due to its rarity. We describe a case of prostatic stromal sarcoma in a 63 year-old man who suffered from urinary obstructive symptoms. Palliative transuterine resection was performed and the preliminary histopathological diagnosis was neuroendocrine carcinoma. After chemotherapy, total pelvic exenteration was performed. Histopathologically, the tumor was composed of monotonously proliferating small to medium-sized round cells, which existed in compact islands with loose or dense fibrovascular networks. Immunohistochemically, the tumor cells were widely positive for vimentin, CD56, CD99 and focally positive for synaptophysin, CD10, progesterone receptor, desmin and CD34, but negative for EMA, cytokeratin, estrogen receptor, S-100 and myoglobin. Most of the previously reported tumors exhibited positive stainability for CD10 and progesterone receptor. In addition to these markers, expressions of CD56, CD99 and synaptophysin were characteristically detected in our case. To the best of our knowledge, we present the first case of prostatic stromal sarcoma with characteristic immunohistochemical staining properties. Although the biological characteristics of this rare tumor have not yet been elucidated, these findings suggest prostatic stromal sarcoma can potentially show neuroectodermal differentiation. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7291874028051262

  2. Gastrointestinal stromal tumour presenting as gastroduodenal intussusception.

    Wilson, Mark H

    2012-08-01

    Gastroduodenal intussusception secondary to gastrointestinal stromal tumour is a very rare cause for intestinal obstruction. The diagnosis of this condition can be challenging, as symptoms are often non-specific and intermittent. This article reports a case where the diagnosis was made preoperatively with abdominal imaging and was treated by a combination of endoscopic reduction and laparoscopic resection.

  3. Pseudoangiomatous stromal hyperplasia (PASH): a brief review.

    Jaunoo, S S; Thrush, S; Dunn, P

    2011-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a benign entity of the breast and typically found incidentally. It warrants thorough investigation in order to exclude more sinister pathology masquerading as this form of benign breast disease and can often be managed expectantly without the need for surgical intervention. We provide a brief review of the literature on PASH, discussing its clinicopathological features and management. PMID:20887819

  4. Exercise regulation of adipose tissue.

    Stanford, Kristin I; Goodyear, Laurie J

    2016-01-01

    Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue. PMID:27386159

  5. Adipose tissue macrophages: amicus adipem?

    Odegaard, Justin I.; Ganeshan, Kirthana; Chawla, Ajay

    2013-01-01

    Chronic overnutrition drives complex adaptations within both professional metabolic and bystander tissues that, despite intense investigation, are still poorly understood. Xu et al. (2013) now describe the unexpected ability of adipose tissue macrophages to buffer lipids released from obese adipocytes in a manner independent of inflammatory macrophage activation.

  6. Cardiovascular tissue engineering and regeneration based on adipose tissue-derived stem/stromal cells

    Parvizi, Mojtaba

    2016-01-01

    Currently, the pre-clinical field is rapidly progressing in search of new therapeutic modalities that replace or complement current medication to treat cardiovascular disease. Among these are the single or combined use of stem cells, biomaterials and instructive factors, which together form the triad of tissue engineering and regenerative medicine. Stem cell therapy is a promising approach for repair, remodeling and even regenerate tissue of otherwise irreparable damage, such as after myocard...

  7. Quantification of adipose tissue insulin sensitivity

    Søndergaard, Esben; Jensen, Michael D

    2016-01-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute...... to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible...... quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and...

  8. Quantification of adipose tissue insulin sensitivity.

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses. PMID:27073214

  9. Stromal fibrosis reaction in rat prostates induced by alpha 1 adrenergic stimulation.

    Rosenzweig-Bublil, Nurit; Abramovici, Armand

    2006-01-01

    Most of the publications dealing with the experimental induction of prostatic neoplasia have focused on the description of epithelial lesions, but little attention has been paid to the involvement of their stromal alterations. The present study is a first attempt to assess the stromal changes in both collagen and elastic fibrils as well as in its cellular constituents, which accompany prostatic intraepithelial neoplastic (PIN)-like lesions induced by phenylephrine (PE) in rats. Adolescent rats received subcutaneous injections of PE daily (10 mg/kg/d) for 1 month. At the end of the experimental period the rats were sacrificed; the dissected ventral prostates were fixed in Stieve solution and paraffin-embedded; and sections were cut and stained accordingly. Most of the stromal cells were identified by immunohistochemistry techniques using primary antibodies to ED2 (resident macrophages), actin (fibrocytes and vascular smooth muscle cells), vimentin (mesenchymal cells), and 5'-bromo-2'-deoxyuridine (S-phase proliferating cells). Collagen stromal mass was visualized by Gomori trichrome and individual collagen fibers by picrosirius red staining under polarized light, whereas the fine fibrils were stained according to the Pinkus method. The untreated rat prostates are characterized by a delicate interacinar stroma with scanty cells and fibrils. The PE-treated prostates showed a significant increase in both cellular and fibrillar elements as well as an increase in arteriolar density, in addition to the typical PIN lesions. The presence of such an interstitial fibrosis, which also includes inflammatory cells, neoangiogenesis, and synthesis de novo of collagen and fibers, might be regarded as a desmoplastic reaction. It is suggested that these changes could be related to a tissue repair process occurring subsequent to the inflammatory exudate that takes place during the incipient phases of the PE treatment. PMID:16304211

  10. Angiomyxolipoma (vascular myxolipoma) of the knee in a 9-year-old boy

    Angiomyxolipoma (vascular myxolipoma) is a very rare variant of lipoma. This tumor is characterized by mature adipose tissue mixed with myxoid stroma and vascular vessels. To date, nine cases have been reported, all of them occurring in adults. Herein, we report a unique case of a 9-year-old boy presenting with a solitary painful mass on the right medial thigh and illustrate the imaging characteristics of this rare tumor. (orig.)

  11. Angiomyxolipoma (vascular myxolipoma) of the knee in a 9-year-old boy

    Kim, Hye Jeong; Yang, Ik; Jung, Ah Young [Kangnam Sacred Heart Hospital, Department of Radiology, Seoul (Korea, Republic of); Hwang, Ji Hyo [Hallym University College of Medicine, Department of Orthopedic Surgery, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of); Shin, Mi Kyung [Hallym University College of Medicine, Department of Pathology, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of)

    2010-12-15

    Angiomyxolipoma (vascular myxolipoma) is a very rare variant of lipoma. This tumor is characterized by mature adipose tissue mixed with myxoid stroma and vascular vessels. To date, nine cases have been reported, all of them occurring in adults. Herein, we report a unique case of a 9-year-old boy presenting with a solitary painful mass on the right medial thigh and illustrate the imaging characteristics of this rare tumor. (orig.)

  12. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism1

    Galie, Mirco; Farace, Paolo; Nanni, Cristina; Spinelli, Antonello; Nicolato, Elena; Boschi, Federico; Magnani, Paolo; Trespidi, Silvia; Ambrosini, Valentina; Fanti, Stefano; Merigo, Flavia; Osculati, Francesco; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular ...

  13. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues

    Pellegrinelli, Vanessa; Carobbio, Stefania; VIDAL-PUIG, Antonio

    2016-01-01

    White adipose tissue (WAT) has key metabolic and endocrine functions and plays a role in regulating energy homeostasis and insulin sensitivity. WAT is characterised by its capacity to adapt and expand in response to surplus energy through processes of adipocyte hypertrophy and/or recruitment and proliferation of precursor cells in combination with vascular and extracellular matrix remodelling. However, in the context of sustained obesity, WAT undergoes fibro-inflammation, which compromises it...

  14. 脂肪组织来源干细胞的分化潜能和应用%DIFFERENTIATION POTENTIAL AND APPLICATION OF STEM CELLS FROM ADIPOSE TISSUE

    史琳丽; 杨向群

    2012-01-01

    目的 介绍脂肪组织来源的干细胞种类、分化潜能及在再生医学中的应用和优势. 方法 广泛查阅近年关于BMSCs、脂肪来源干细胞(adipose-derived stem cells,ADSCs)和去分化脂肪(dedifferentiated fat,DFAT)细胞的实验研究及临床研究文献,并进行整理、综合与分析. 结果 从脂肪基质成分可以分离得到ADSCs,ADSCs具有多向分化潜能,可分化为脂肪、骨、软骨、内皮、肌以及神经细胞等,并已较成功地应用于再生医学各领域.成熟脂肪细胞经过天花板培养法可以去分化为成纤维样细胞,即DFAT细胞,获得了多向分化潜能,也可以像ADSCs一样分化为脂肪、骨、软骨、内皮、肌以及神经细胞等.相比较目前常用的成体干细胞BMSCs,ADSCs、DFAT细胞来源广泛、取材更容易;而相对于ADSCs,DFAT细胞均一性高,增殖能力强. 结论 脂肪组织作为人体干细胞的重要来源,可能会给临床组织缺损的修复与再生带来新希望.%Objective To introduce types and differentiation potentials of stem cells from adipose tissue, and its applications on regenerative medicine and advantages. Methods The literature of original experimental study and clinical research about bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), and dedifferentiated fat (DFAT) cells was extensively reviewed and analyzed. Results ADSCs can be isolated from stromal vascular fraction. As ADSCs have multi-lineage potentials, such as adipogenesis, osteogenesis, chondrogenesis, angiogenesis, myogenesis, and neurogenesis, they have already been successfully used in regenerative medicine areas. Dramatically, mature fat cells can be dedifferentiated and changed into fibroblast-like cells, named DFAT cells, via ceiling culture method. DFAT cells also had the same multi-lineage potentials as ADSCs, differentiating into adipocytes, osteocytes, chondrocytes, endothelial cells, muscle cells, and nerve cells. Compared

  15. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues.

    Pellegrinelli, Vanessa; Carobbio, Stefania; Vidal-Puig, Antonio

    2016-06-01

    White adipose tissue (WAT) has key metabolic and endocrine functions and plays a role in regulating energy homeostasis and insulin sensitivity. WAT is characterised by its capacity to adapt and expand in response to surplus energy through processes of adipocyte hypertrophy and/or recruitment and proliferation of precursor cells in combination with vascular and extracellular matrix remodelling. However, in the context of sustained obesity, WAT undergoes fibro-inflammation, which compromises its functionality, contributing to increased risk of type 2 diabetes and cardiovascular diseases. Conversely, brown adipose tissue (BAT) and browning of WAT represent potential therapeutic approaches, since dysfunctional white adipocyte-induced lipid overspill can be halted by BAT/browning-mediated oxidative anti-lipotoxic effects. Better understanding of the cellular and molecular pathophysiological mechanisms regulating adipocyte size, number and depot-dependent expansion has become a focus of interest over recent decades. Here, we summarise the mechanisms contributing to adipose tissue (AT) plasticity and function including characteristics and cellular complexity of the various adipose depots and we discuss recent insights into AT origins, identification of adipose precursors, pathophysiological regulation of adipogenesis and its relation to WAT/BAT expandability in obesity and its associated comorbidities. PMID:27039901

  16. Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

    do Valle Gomes-Gatto, Camila; Duarte, Fernanda Oliveira; Stotzer, Uliana Sbeguen; Rodrigues, Maria Fernanda Cury; de Andrade Perez, Sérgio Eduardo; Selistre-de-Araujo, Heloisa Sobreiro

    2016-01-01

    OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats.

  17. Ectopic Pancreas Imitating Gastrointestinal Stromal Tumor (GIST) In The Stomach.

    Zińczuk, Justyna; Bandurski, Roman; Pryczynicz, Anna; Konarzewska-Duchnowska, Emilia; Kemona, Andrzej; Kędra, Bogusław

    2015-05-01

    Ectopic pancreas is a rare congenital disorder defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. Most cases of ectopic pancreas are asymptomatic, but it may become clinically evident depending on the size, location and the pathological changes similar to those observed in case of the normal pancreas. It is often an incidental finding and can be located at different sites in the gastrointestinal tract. The most common locations are: the stomach, duodenum or the proximal part of small intestine. The risk of malignancy, bleeding and occlusion are the most serious complications. Despite the development in diagnostics, it still remains a challenge for the clinician to differentiate it from neoplasm. In this report, we described a case of 28-years old woman who presented recurrent epigastric pain. The upper gastrointestinal endoscopy revealed gastrointestinal stromal tumor on the border of the body and antrum of the back wall of great curvature of the stomach. The histopathological examination after surgery showed heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of gastric mass lesions. PMID:26172167

  18. Study on vasculogenic mimicry in malignant esophageal stromal tumors

    Hui Zhao; Xiao-Neng Gu

    2008-01-01

    AIM: To investigate whether malignant esophageal stromaltumors contain PAS-positive patterned matrix-associatedvascular channels, which are lined by tumor cells, but notvascular endothelial cells. That is vasculogenic mimicry(VN) independent of tumor angiogenesis.METHODS: Thirty-six tissue samples of/nalignantesophageal stromal tumors were analyzed. Tissuesections were stained for Vascular endothelial growthfactor (VEGF), CD31 and periodic acid Schiff (PAS). Thelevel of VEGF, the microvascular density (MVD) and thevasculogenic mimicry density (VID) were determined.RESULTS: PAS-positive patterned matrix-associatedvascular channels were detected in 33.3% (12/36)of tumor samples. Within these patterned channels,red blood cells were found. The level of VEGF and theMVD in tumors containing patterned channels weresignificantly higher than those in tumors not containingpatterned channels (P < 0.05). At the same time, themalignant degree of tumors was higher, the proportionsof tumors containing patterned channels were not onlymore, but also in the each kind of tumors containingpatterned channels.CONCLUSION: In malignant esophageal stromaltumors, a VM mechanism causes some tumor cells todeform themselves and secrete extracellular matrix;thus, PAS-positive patterned matrix-associated vascularchannels appear and supplying blood to the tumors tosustain their growth and metastasis.

  19. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism1

    Galie, Mirco; Farace, Paolo; Nanni, Cristina; Spinelli, Antonello; Nicolato, Elena; Boschi, Federico; Magnani, Paolo; Trespidi, Silvia; Ambrosini, Valentina; Fanti, Stefano; Merigo, Flavia; Osculati, Francesco; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition. PMID:18030358

  20. CT-demonstration of adipose tissue of the sinus cavernosus

    Adipose bodies of the sinus cavernosus - the only genuine intracranial adipose tissue - can be demonstrated well by CT. They appear as polymorph well defined hypodense objects in unilateral or bilateral manifestation. Adipose bodies most frequently show a size between 4 and 9 mm and densities about -20 to -40 HE. Occasionally the adipose bodies directly lead into the adipose tissue of the orbit. (orig.)

  1. Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction

    Marco Calogero Amato

    2014-01-01

    Full Text Available The Visceral Adiposity Index (VAI has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk.

  2. Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis

    Semon, Julie A.; Maness, Catherine; Zhang, Xiujuan; Sharkey, Steven A.; Beuttler, Marc M; Shah, Forum S.; Pandey, Amitabh C; Gimble, Jeffrey M.; Zhang, Shijia; Scruggs, Brittni A; Strong, Amy L.; Strong, Thomas A; Bunnell, Bruce A.

    2014-01-01

    Introduction While administration of ex vivo culture-expanded stem cells has been used to study immunosuppressive mechanisms in multiple models of autoimmune diseases, less is known about the uncultured, nonexpanded stromal vascular fraction (SVF)-based therapy. The SVF is composed of a heterogeneous population of cells and has been used clinically to treat acute and chronic diseases, alleviating symptoms in a range of tissues and organs. Methods In this study, the ability of human SVF cells ...

  3. Collagen vascular disease

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this page, ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many of many ...

  4. Heart and vascular services

    ... branch of medicine that focuses on the cardiovascular system. ... Circulatory system; Vascular system; Cardiovascular system ... to diagnose, monitor or treat diseases of the circulatory and vascular system include: Cardiac CT for calcium scoring Cardiac MRI ...

  5. The adipose organ at a glance

    Saverio Cinti

    2012-09-01

    Full Text Available The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.

  6. Hounsfield unit dynamics of adipose tissue and non-adipose soft tissue in growing pigs

    Mcevoy, Fintan; Madsen, Mads T.; Strathe, Anders Bjerring;

    2008-01-01

    Changes in the Hounsfield Unit value of adipose tissue and of no-adipose soft tissue during growth are poorly documented. This study examines the HU of these tissues in growing pigs.......Changes in the Hounsfield Unit value of adipose tissue and of no-adipose soft tissue during growth are poorly documented. This study examines the HU of these tissues in growing pigs....

  7. Imaging spectrum of gastrointestinal stromal tumor

    Binit Sureka

    2014-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs were first described by Clark and Mazur in 1983 for smooth muscle neoplasms of the gastrointestinal tract differentiating them from leiomyoma, leiomyosarcomas and neurogenic tumors. GISTs can arise from the bowel, peritoneum, omentum or retroperitoneum. This article reviews the computed tomography imaging features of primary GISTs, response to treatment and highlights data on predicting the outcome to chemotherapeutic drugs on imaging.

  8. Genetic analysis of ovarian microcystic stromal tumor

    Lee, Jae Hoon; Kim, Hyun-Soo; Cho, Nam Hoon; Lee, Jung-Yun; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji

    2016-01-01

    Microcystic stromal tumor (MCST) of the ovary is a rare subtype of ovarian tumor first described in 2009. Although high nuclear expression of β-catenin and β-catenin gene (CTNNB1) mutation are related with ovarian MCST, the origin and genetic background of ovarian MCST remain unclear. In this study, two cases of ovarian MCST are presented. Microscopically, the tumors showed a microcystic pattern and regions with lobulated cellular masses with intervening hyalinized, fibrous stroma. Tumor cell...

  9. Skull metastasis from rectal gastrointestinal stromal tumours.

    Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica

    2009-09-01

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach. PMID:19776004

  10. Computed tomography in gastrointestinal stromal tumors

    The aim of this study was to define the imaging characteristics of primary and recurrent gastrointestinal stromal tumors (GIST) in computed tomography with respect to the tumor size. Computed tomography was performed in 35 patients with histologically confirmed gastrointestinal stromal tumors and analyzed retrospectively by two experienced and independent radiologist. The following morphologic tumor characteristics of primary (n=20) and (n=16) recurrent tumors were evaluated according to tumor size, shape, homogeneity, density compared with liver, contrast enhancement, presence of calcifications, ulcerations, fistula or distant metastases and the anatomical relationship to the intestinal wall, and the infiltration of adjacent visceral organs. Small GIST (5-10 cm) demonstrated an irregular shape, inhomogeneous density on unenhanced and contrast-enhanced images, a combined intra- and extraluminal tumor growth with aggressive findings, and infiltration of adjacent organs in 9 primary diagnosed and 2 recurrent tumors. Large GIST (>10 cm), which were observed in 8 primary tumors and 11 recurrent tumors, showed an irregular margin with inhomogeneous density and aggressive findings, and were characterized by signs of malignancy such as distant and peritoneal metastases. Small recurrent tumors had a similar appearance as compared with large primary tumors. Computed tomography gives additional information with respect to the relationship of gastrointestinal stromal tumor to the gastrointestinal wall and surrounding organs, and it detects distant metastasis. Primary and recurrent GIST demonstrate characteristic CT imaging features which are related to tumor size. Aggressive findings and signs of malignancy are found in larger tumors and in recurrent disease. Computed tomography is useful in detection and characterization of primary and recurrent tumors with regard to tumor growth pattern, tumor size, and varied appearances of gastrointestinal stromal tumors, and indirectly

  11. Computed tomography in gastrointestinal stromal tumors

    Ghanem, Nadir; Altehoefer, Carsten; Winterer, Jan; Schaefer, Oliver; Springer, Oliver; Kotter, Elmar; Langer, Mathias [Department of Diagnostic Radiology, University Hospital Freiburg, Hugstetter Strasse 55, 79106, Freiburg (Germany); Furtwaengler, Alex [Department of Abdominal Surgery, University Hospital Freiburg, Hugstetter Strasse 55, 79106, Freiburg (Germany)

    2003-07-01

    The aim of this study was to define the imaging characteristics of primary and recurrent gastrointestinal stromal tumors (GIST) in computed tomography with respect to the tumor size. Computed tomography was performed in 35 patients with histologically confirmed gastrointestinal stromal tumors and analyzed retrospectively by two experienced and independent radiologist. The following morphologic tumor characteristics of primary (n=20) and (n=16) recurrent tumors were evaluated according to tumor size, shape, homogeneity, density compared with liver, contrast enhancement, presence of calcifications, ulcerations, fistula or distant metastases and the anatomical relationship to the intestinal wall, and the infiltration of adjacent visceral organs. Small GIST (<5 cm) showed a sharp tumor margin with homogeneous density and structure on unenhanced and contrast-enhanced images, and were characterized by an intraluminal tumor growth. Intermediate sized GIST (>5-10 cm) demonstrated an irregular shape, inhomogeneous density on unenhanced and contrast-enhanced images, a combined intra- and extraluminal tumor growth with aggressive findings, and infiltration of adjacent organs in 9 primary diagnosed and 2 recurrent tumors. Large GIST (>10 cm), which were observed in 8 primary tumors and 11 recurrent tumors, showed an irregular margin with inhomogeneous density and aggressive findings, and were characterized by signs of malignancy such as distant and peritoneal metastases. Small recurrent tumors had a similar appearance as compared with large primary tumors. Computed tomography gives additional information with respect to the relationship of gastrointestinal stromal tumor to the gastrointestinal wall and surrounding organs, and it detects distant metastasis. Primary and recurrent GIST demonstrate characteristic CT imaging features which are related to tumor size. Aggressive findings and signs of malignancy are found in larger tumors and in recurrent disease. Computed tomography

  12. Drug Repurposing for Gastrointestinal Stromal Tumor

    Pessetto, Ziyan Y.; Weir, Scott J.; Sethi, Geetika; Broward, Melinda A.; Andrew K Godwin

    2013-01-01

    Despite significant treatment advances over the past decade, metastatic gastrointestinal stromal tumor (GIST) remains largely incurable. Rare diseases, such as GIST, individually affect small groups of patients but collectively are estimated to affect 25–30 million people in the U.S. alone. Given the costs associated with the discovery, development and registration of new drugs, orphan diseases such as GIST are often not pursued by mainstream pharmaceutical companies. As a result, “drug repur...

  13. Corneal Stromal Bioequivalents Secreted on Patterned Silk Substrates

    Wu, Jian; Rnjak-Kovacina, Jelena; Du, Yiqin; Funderburgh, Martha L.; Kaplan, David L.; Funderburgh, James L.

    2014-01-01

    Emulating corneal stromal tissue is believed to be the most challenging step in bioengineering an artificial human cornea because of the difficulty in reproducing its highly ordered microstructure, the key to the robust biomechanical properties and optical transparency of this tissue. We conducted a comparative study to assess the feasibility of human corneal stromal stem cells (hCSSCs) and human corneal fibroblasts (hCFs) in the generation of human corneal stromal tissue on groove-patterned ...

  14. Metanephric stromal tumor: A novel pediatric renal neoplasm

    Rajalakshmi V; Chandran Philip; Selvambigai,; Ganesh Jai

    2009-01-01

    Metanephric stromal tumor of kidney is a novel pediatric benign stromal specific renal neoplasm. A few cases have been reported in adults also. This tumor is usually centered in the renal medulla with a characteristic microscopic appearance which differentiates this lesion from congenital mesoblastic nephroma and clear cell sarcoma of the kidney. In most cases complete excision alone is curative. The differentiation of metanephric stromal tumor from clear cell sarcoma of the kidney will spare...

  15. Immunoregulatory effects of placenta-derived decidual stromal cells

    Erkers, Tom

    2016-01-01

    Decidual stromal cells (DSCs) play a pivotal role in feto-maternal tolerance to prevent rejection of the fetus during pregnancy. This provides a rationale for immunomodulatory stromal cells from the placenta being isolated and used as cellular therapy for inflammatory conditions following hematopoietic stem cell transplantation (HSCT). The term placenta provides a ready source of cells, since this tissue is normally discarded after delivery. Stromal cells were isolated from different pa...

  16. Biochemistry of adipose tissue: an endocrine organ

    Coelho, Marisa; Oliveira, Teresa; Fernandes, Rúben

    2013-01-01

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of n...

  17. Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease

    Shah, Arti; Mehta, Nehal; Reilly, Muredach P.

    2008-01-01

    Adiposity-associated inflammation and insulin resistance are strongly implicated in the development of type 2 diabetes and atherosclerotic cardiovascular disease. This article reviews the mechanisms of adipose inflammation, because these may represent therapeutic targets for insulin resistance and for prevention of metabolic and cardiovascular consequences of obesity. The initial insult in adipose inflammation and insulin resistance, mediated by macrophage recruitment and endogenous ligand ac...

  18. Stromal reengineering to treat pancreas cancer.

    Stromnes, Ingunn M; DelGiorno, Kathleen E; Greenberg, Philip D; Hingorani, Sunil R

    2014-07-01

    Pancreatic ductal adenocarcinoma co-opts multiple cellular and extracellular mechanisms to create a complex cancer organ with an unusual proclivity for metastasis and resistance to therapy. Cell-autonomous events are essential for the initiation and maintenance of pancreatic ductal adenocarcinoma, but recent studies have implicated critical non-cell autonomous processes within the robust desmoplastic stroma that promote disease pathogenesis and resistance. Thus, non-malignant cells and associated factors are culprits in tumor growth, immunosuppression and invasion. However, even this increasing awareness of non-cell autonomous contributions to disease progression is tempered by the conflicting roles stromal elements can play. A greater understanding of stromal complexity and complicity has been aided in part by studies in highly faithful genetically engineered mouse models of pancreatic ductal adenocarcinoma. Insights gleaned from such studies are spurring the development of therapies designed to reengineer the pancreas cancer stroma and render it permissive to agents targeting cell-autonomous events or to reinstate immunosurveillance. Integrating conventional and immunological treatments in the context of stromal targeting may provide the key to a durable clinical impact on this formidable disease. PMID:24908682

  19. Stromal tumor of colon: Case report

    Nićiforović Dijana

    2008-01-01

    Full Text Available Introduction Gastrointestinal stromal tumor is relatively new term, it can be localized anywhere inside the gastrointestinal system. It has formerly been called leiomyoma, leiomyoblastoma, and/or leiomyosarcoma. Case report Case report is about a female patient with indefinite difficulties described as 'bother', mild anemia and anamnesis data of her mother who had been operated on for colon tumor. After blood examination, which had shown values within referential limits except for mild anemia, patient underwent radiological examination. Primarily, an abdominal cavity ultrasound had been performed, where a suspicious formation in the right hemiabdomen was found, but without distinctive anatomical localization in the abdominal cavity. Secondly, a checkup by Duplex Doppler ultrasound was made, as well as radiological examination with double contrast of colon and computed tomography, where tumor was visualized on ascendant colon with extraluminal localization. Discussion Radiological findings were confirmed by surgery. Histopathological findings were positive for gastrointestinal stromal colon tumor. Conclusion Gastrointestinal stromal tumors represent extremely rare tumors of gastrointestinal system, especially when localized at the colon, but they should be included in a differential diagnosis for their malignant potential.

  20. How to Prevent Vascular Disease

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  1. Metanephric stromal tumor: A novel pediatric renal neoplasm

    Rajalakshmi V

    2009-07-01

    Full Text Available Metanephric stromal tumor of kidney is a novel pediatric benign stromal specific renal neoplasm. A few cases have been reported in adults also. This tumor is usually centered in the renal medulla with a characteristic microscopic appearance which differentiates this lesion from congenital mesoblastic nephroma and clear cell sarcoma of the kidney. In most cases complete excision alone is curative. The differentiation of metanephric stromal tumor from clear cell sarcoma of the kidney will spare the child from the ill effects of adjuvant chemotherapy. In this communication we describe the gross and microscopic features of metanephric stromal tumor in a one-month-old child with good prognosis.

  2. Collagen-hyaluronic acid scaffolds for adipose tissue engineering.

    Davidenko, N; Campbell, J J; Thian, E S; Watson, C J; Cameron, R E

    2010-10-01

    Three-dimensional (3-D) in vitro models of the mammary gland require a scaffold matrix that supports the development of adipose stroma within a robust freely permeable matrix. 3-D porous collagen-hyaluronic acid (HA: 7.5% and 15%) scaffolds were produced by controlled freeze-drying technique and crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride. All scaffolds displayed uniform, interconnected pore structure (total porosity approximately 85%). Physical and chemical analysis showed no signs of collagen denaturation during the formation process. The values of thermal characteristics indicated that crosslinking occurred and that its efficiency was enhanced by the presence of HA. Although the crosslinking reduced the swelling of the strut material in water, the collagen-HA matrix as a whole tended to swell more and show higher dissolution resistance than pure collagen samples. The compressive modulus and elastic collapse stress were higher for collagen-HA composites. All the scaffolds were shown to support the proliferation and differentiation 3T3-L1 preadipocytes while collagen-HA samples maintained a significantly increased proportion of cycling cells (Ki-67+). Furthermore, collagen-HA composites displayed significantly raised Adipsin gene expression with adipogenic culture supplementation for 8 days vs. control conditions. These results indicate that collagen-HA scaffolds may offer robust, freely permeable 3-D matrices that enhance mammary stromal tissue development in vitro. PMID:20466086

  3. Anti-angiogenesis therapy based on the bone marrow-derived stromal cells genetically engineered to express sFlt-1 in mouse tumor model

    Chen X-C; Luo Y.; Wu Y; Zhang X-W; Wang R; Jia Y-Q; Teng H; Yang J-L; Hu M; Zhang R.; Tian L; Zhao X; Wei Y-Q

    2008-01-01

    Abstract Background Bone marrow-derived stromal cells (BMSCs) are important for development, tissue cell replenishment, and wound healing in physiological and pathological conditions. BMSCs were found to preferably reach sites undergoing the process of cell proliferation, such as wound and tumor, suggesting that BMSCs may be used as a vehicle for gene therapy of tumor. Methods Mouse BMSCs were loaded with recombinant adenoviruses which express soluble Vascular Endothelial Growth Factor Recept...

  4. Adipose VEGF Links the White-to-Brown Fat Switch With Environmental, Genetic, and Pharmacological Stimuli in Male Mice.

    During, Matthew J; Liu, Xianglan; Huang, Wei; Magee, Daniel; Slater, Andrew; McMurphy, Travis; Wang, Chuansong; Cao, Lei

    2015-06-01

    Living in an enriched environment (EE) decreases adiposity, increases energy expenditure, causes resistance to diet induced obesity, and induces brown-like (beige) cells in white fat via activating a hypothalamic-adipocyte axis. Here we report that EE stimulated vascular endothelial growth factor (VEGF) expression in a fat depot-specific manner prior to the emergence of beige cells. The VEGF up-regulation was independent of hypoxia but required intact sympathetic tone to the adipose tissue. Targeted adipose overexpression of VEGF reproduced the browning effect of EE. Adipose-specific VEGF knockout or pharmacological VEGF blockade with antibodies abolished the induction of beige cell by EE. Hypothalamic brain-derived neurotrophic factor stimulated by EE regulated the adipose VEGF expression, and VEGF signaling was essential to the hypothalamic brain-derived neurotrophic factor-induced white adipose tissue browning. Furthermore, VEGF signaling was essential to the beige cells induction by exercise, a β3-adrenergic agonist, and a peroxisome proliferator-activated receptor-γ ligand, suggesting a common downstream pathway integrating diverse upstream mechanisms. Exploiting this pathway may offer potential therapeutic interventions to obesity and metabolic diseases. PMID:25763639

  5. Biologically and mechanically driven design of an RGD-mimetic macroporous foam for adipose tissue engineering applications.

    Rossi, Eleonora; Gerges, Irini; Tocchio, Alessandro; Tamplenizza, Margherita; Aprile, Paola; Recordati, Camilla; Martello, Federico; Martin, Ivan; Milani, Paolo; Lenardi, Cristina

    2016-10-01

    Despite clinical treatments for adipose tissue defects, in particular breast tissue reconstruction, have certain grades of efficacy, many drawbacks are still affecting the long-term survival of new formed fat tissue. To overcome this problem, in the last decades, several scaffolding materials have been investigated in the field of adipose tissue engineering. However, a strategy able to recapitulate a suitable environment for adipose tissue reconstruction and maintenance is still missing. To address this need, we adopted a biologically and mechanically driven design to fabricate an RGD-mimetic poly(amidoamine) oligomer macroporous foam (OPAAF) for adipose tissue reconstruction. The scaffold was designed to fulfil three fundamental criteria: capability to induce cell adhesion and proliferation, support of in vivo vascularization and match of native tissue mechanical properties. Poly(amidoamine) oligomers were formed into soft scaffolds with hierarchical porosity through a combined free radical polymerization and foaming reaction. OPAAF is characterized by a high water uptake capacity, progressive degradation kinetics and ideal mechanical properties for adipose tissue reconstruction. OPAAF's ability to support cell adhesion, proliferation and adipogenesis was assessed in vitro using epithelial, fibroblast and endothelial cells (MDCK, 3T3L1 and HUVEC respectively). In addition, in vivo subcutaneous implantation in murine model highlighted OPAAF potential to support both adipogenesis and vessels infiltration. Overall, the reported results support the use of OPAAF as a scaffold for engineered adipose tissue construct. PMID:27428768

  6. Stromal Cells in Dense Collagen Promote Cardiomyocyte and Microvascular Patterning in Engineered Human Heart Tissue.

    Roberts, Meredith A; Tran, Dominic; Coulombe, Kareen L K; Razumova, Maria; Regnier, Michael; Murry, Charles E; Zheng, Ying

    2016-04-01

    Cardiac tissue engineering is a strategy to replace damaged contractile tissue and model cardiac diseases to discover therapies. Current cardiac and vascular engineering approaches independently create aligned contractile tissue or perfusable vasculature, but a combined vascularized cardiac tissue remains to be achieved. Here, we sought to incorporate a patterned microvasculature into engineered heart tissue, which balances the competing demands from cardiomyocytes to contract the matrix versus the vascular lumens that need structural support. Low-density collagen hydrogels (1.25 mg/mL) permit human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to form a dense contractile tissue but cannot support a patterned microvasculature. Conversely, high collagen concentrations (density ≥6 mg/mL) support a patterned microvasculature, but the hESC-CMs lack cell-cell contact, limiting their electrical communication, structural maturation, and tissue-level contractile function. When cocultured with matrix remodeling stromal cells, however, hESC-CMs structurally mature and form anisotropic constructs in high-density collagen. Remodeling requires the stromal cells to be in proximity with hESC-CMs. In addition, cocultured cardiac constructs in dense collagen generate measurable active contractions (on the order of 0.1 mN/mm(2)) and can be paced up to 2 Hz. Patterned microvascular networks in these high-density cocultured cardiac constructs remain patent through 2 weeks of culture, and hESC-CMs show electrical synchronization. The ability to maintain microstructural control within engineered heart tissue enables generation of more complex features, such as cellular alignment and a vasculature. Successful incorporation of these features paves the way for the use of large scale engineered tissues for myocardial regeneration and cardiac disease modeling. PMID:26955856

  7. Intra-abdominal fat. Part I. The images of the adipose tissue localized beyond organs.

    Smereczyński, Andrzej; Kołaczyk, Katarzyna; Bernatowicz, Elżbieta

    2015-09-01

    Unaltered fat is a permanent component of the abdominal cavity, even in slim individuals. Visceral adiposity is one of the important factors contributing to diabetes, cardiovascular diseases and certain neoplasms. Moreover, the adipose tissue is an important endocrine and immune organ of complex function both when normal and pathological. Its role in plastic surgery, reconstruction and transplantology is a separate issue. The adipose tissue has recently drawn the attention of research institutes owing to being a rich source of stem cells. This review, however, does not include these issues. The identification of fat is relatively easy using computed tomography and magnetic resonance imaging. It can be more difficult in an ultrasound examination for several reasons. The aim of this paper is to present various problems associated with US imaging of unaltered intra-abdominal fat located beyond organs. Based on the literature and experience, it has been demonstrated that the adipose tissue in the abdominal cavity has variable echogenicity, which primarily depends on the amount of extracellular fluid and the number of connective tissue septa, i.e. elements that potentiate the number of areas that reflect and scatter ultrasonic waves. The normal adipose tissue presents itself on a broad gray scale: from a hyperechoic area, through numerous structures of lower reflection intensity, to nearly anechoic regions mimicking the presence of pathological fluid collections. The features that facilitate proper identification of this tissue are: sharp margins, homogeneous structure, high compressibility under transducer pressure, no signs of infiltration of the surrounding structures and no signs of vascularization when examined with the color and power Doppler. The accumulation of fat tissue in the abdominal cavity can be generalized, regional or focal. The identification of the adipose tissue in the abdominal cavity using ultrasonography is not always easy. When in doubt, the

  8. Development and differentiation of adipose tissue

    Ivković-Lazar Tatjana A.

    2003-01-01

    Full Text Available Introduction For years adipose tissue has been considered inert, serving only as a depot of energy surplus. However, there have been recent changes, undoubtedly due to advancement of methods for studying the morphology and metabolic activities of adipose tissue (microdialysis and adipose tissue catheterization. In normal-weight subjects, adipose tissue makes 10-12% with males and 15-20% with females. About 80 % of adipose tissue is located under the skin, and the rest envelops the internal organs. With humans there are white and brown adipose tissues, which is predominant with infants and small children. Histologic characteristics From a histological point of view, it is a special form of reticular connective tissue, which contains adipocytes with netlike structure. Human adipose tissue has four types of adrenergic receptors with different topographic dispositions, which manifest different metabolic activity of adipocytes of particular body organs. Changes in adipose tissue are associated with the process of adipocyte differentiation. Critical moments for this process are last months of pregnancy, the first six months of infancy and then puberty. However, the differentiation process may also begin during maturity. Namely, as size of adipocytes can increase to a certain limit, this process can be activated after reaching a 'critical' adipocyte volume. The differentiation process is affected by a number of hormones (insulin, glucagon, corticosteroids, somatotropin (STH, thyroid gland hormones, prolactin, testosterone, but also by some other substances (fatty acids, prostaglandins, liposoluble vitamins, butyrate, aspirin, indomethacin, metylxanthine, etc..

  9. Capillary permeability in adipose tissue

    Paaske, W P; Nielsen, S L

    1976-01-01

    A method for measurement of capillary permeability using external registration of gamma emitting isotopes after close arterial bolus injection was applied to the isolated inguinal fat pad in slightly fasting rabbits. An average extraction of 26 per cent for 51Cr-EDTA was found at a plasma flow of...... about 7 ml/100 g-min. This corresponds to a capillary diffusion capacity of 2.0 ml/100 g-min which is half the value reported for vasodilated skeletal muscle having approximately twice as great capillary surface area. Thus, adipose tissue has about the same capillary permeability during slight metabolic...

  10. Osteogenic Potential of Mouse Adipose-Derived Stem Cells Sorted for CD90 and CD105 In Vitro

    Maiko Yamamoto

    2014-01-01

    Full Text Available Adipose tissue-derived stromal cells, termed ASCs, play an important role in regenerative applications. They resemble mesenchymal stem cells owing to their inexhaustibility, general differentiation potential, and plasticity and display a series of cell-specific and cluster-of-differentiation (CD marker profiles similar to those of other somatic stem cells. Variations in phenotypes or differentiation are intimately associated with CD markers. The purpose of our study was to exhibit distinct populations of ASCs with differing characteristics for osteogenic differentiation. The primary cell batch of murine-derived ASCs was extracted from subcutaneous adipose tissue and the cells were sorted for the expression of the surface protein molecules CD90 and CD105 using flow cytometry. Each cell population sorted for CD90 and CD105 was analyzed for osteogenic potency after cell culture. The results suggested that ASCs exhibit distinct populations with differing characteristics for osteogenic differentiation: unsorted ASCs stimulated comparable mineralized nodule formation as bone marrow stromal cells (BMSCs in osteogenic medium and viral transfection for BMP2 accelerated the formation of mineralized nodules in CD90 and/or CD105 positive ASCs with observation of decrease in CD105 expression after 14 days. Future studies assessing different immunophenotypes of ASCs should be undertaken to develop cell-based tissue engineering.

  11. Metabolism of stromal and immune cells in health and disease

    Ghesquière, Bart; Wong, Brian W.; Kuchnio, Anna; Carmeliet, Peter

    2014-01-01

    Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function.

  12. Imaging Pediatric Vascular Lesions

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  13. Imaging Pediatric Vascular Lesions.

    Nguyen, Tuyet A; Krakowski, Andrew C; Naheedy, John H; Kruk, Peter G; Friedlander, Sheila Fallon

    2015-12-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  14. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    Anna Meiliana

    2014-08-01

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

  15. Stromal cell contribution to human follicular lymphoma pathogenesis.

    Mourcin, Frédéric; Pangault, Céline; Amin-Ali, Rada; Amé-Thomas, Patricia; Tarte, Karin

    2012-01-01

    Follicular lymphoma (FL) is the prototypical model of indolent B cell lymphoma displaying a strong dependence on a specialized cell microenvironment mimicking normal germinal center. Within malignant cell niches in invaded lymph nodes and bone marrow, external stimuli provided by infiltrating stromal cells make a pivotal contribution to disease development, progression, and drug resistance. The crosstalk between FL B cells and stromal cells is bidirectional, causing activation of both partners. In agreement, FL stromal cells exhibit specific phenotypic, transcriptomic, and functional properties. This review highlights the critical pathways involved in the direct tumor-promoting activity of stromal cells but also their role in the organization of FL cell niche through the recruitment of accessory immune cells and their polarization to a B cell supportive phenotype. Finally, deciphering the interplay between stromal cells and FL cells provides potential new therapeutic targets with the aim to mobilize malignant cells outside their protective microenvironment and increase their sensitivity to conventional treatment. PMID:22973275

  16. Identification of the 64 kilodalton chloroplast stromal phosphoprotein as phosphoglucomutase

    Phosphorylation of the 64 kilodalton stromal phosphoprotein by incubation of pea (Pisum sativum) chloroplast extracts with [γ-32P]ATP decreased in the presence of Glc-6-P and Glc-1,6-P2, but was stimulated by glucose. Two-dimensional gel electrophoresis following incubation of intact chloroplasts and stromal extracts with [γ-32P]ATP, or incubation of stromal extracts and partially purified phosphoglucomutase (EC 2.7.5.1) with [32P]Glc-1-P showed that the identical 64 kilodalton polypeptide was labeled. A 62 kilodalton polypeptide was phosphorylated by incubation of tobacco (Nicotiana sylvestris) stromal extracts with either [γ-32P]ATP or [32P]Glc-1-P. In contrast, an analogous polypeptide was not phosphorylated in extracts from a tobacco mutant deficient in plastid phosphoglucomutase activity. The results indicate that the 64 (or 62) kilodalton chloroplast stromal phosphoprotein is phosphoglucomutase

  17. Radiosensitivities of immune organs' stromal progenitors

    By using the technique of culture of immuno-stromal progenitors in vitro, we studied their radiosensitivities after irradiation in various doses. The values of D0 and n of thymus, spleen and lymph node were 2.3 Gy and 1.5, 2.8 Gy and 1.2, 2.7 Gy and 1.4 respectively. The radiosensitivity of the CFU-F subgroups which formed dense colonies was significantly higher than that of loose colonies, when cultured in vitro

  18. Gastrointestinal stromal tumor and its targeted therapeutics

    Jheri Dupart; Wei Zhang; Jonathan C. Trent

    2011-01-01

    Over the past 60 years, investigators of basic science, pathology, and clinical medicine have studied gastrointestinal stromal tumor (GIST) and made minor advances in patient care. Recent discoveries have led to an understanding of the biological rote of KIT and platelet-derived growth factor receptor-α in GIST and the development of the tyrosine kinase inhibitor imatinib mesylate (Gleevec, formerly STI-571), one of the most exciting examples of targeted therapy to date. The success of targeted therapy in GIST has lead to new developments in our understanding of the medical and surgical management of the disease. Intense study of GIST may lead to new paradigms in the management of cancer.

  19. Gastrointestinal stromal tumour in Meckel's diverticulum

    Patel Mahesh H

    2007-05-01

    Full Text Available Abstract Background Meckel's Diverticulum is the most commonly encountered congenital anomaly of the small intestine, occurring in approximately 2% of the population. Occasionally Meckel's diverticulum harbors neoplasms. Case presentation A 65 year old gentleman, presented with a pelvic mass. On exploratory laparotomy, it turned out to be gastrointestinal stromal tumour (GIST arising from Meckel's diverticulum. Short history and review of literature are discussed. Conclusion Neoplasms occurring from Meckel's diverticulum, even though rare, should be considered as differential diagnosis of pelvic masses arising from bowel, wherever imaging modalities fail to give a definitive diagnosis.

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

    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

  1. Vascularity in thyroid neoplasms

    Larsen, Karen Kjaer; Andersen, Niels Frost; Melsen, Flemming;

    2006-01-01

    The aim of the present study was to evaluate the reliability of four different methods (vascular grading, Chalkley count, microvessel density (MVD) and stereological estimation) for quantifying intratumoral microvascularity in thyroid neoplasms, by comparing the variability within and between...... count should be the preferred method for assessing microvascularity in thyroid neoplasms. The diagnostic evaluation revealed a tendency towards higher degree of vascularity in FA compared to both FC and PC for all methods. No statistically significant association was seen between vascular density and...

  2. Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

    Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

    2009-01-01

    The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions. PMID:19918332

  3. Adiponectin inhibits oxidized low density lipoprotein-induced increase in matrix metalloproteinase 9 expression in vascular smooth muscle cells

    Saneipour, Maryam; Ghatreh-Samani, Keihan; Heydarian, Esfandiar; Farrokhi, Effat; Abdian, Narges

    2015-01-01

    BACKGROUND High expression of matrix metalloproteinase 9 (MMP9) during vascular injury and inflammation plays an important role in atherosclerotic plaque formation and rupture. In the process of atherosclerosis, oxidized low-density lipoprotein (oxLDL) upregulates MMP9 in human aortic vascular smooth muscle cells (HA/VSMCs). Adiponectin is an adipose tissue-derived hormone that has been shown to exert anti-atherogenic and anti-inflammatory effects. The aim of this study was to investigate the...

  4. Clinical-Grade Manufacturing of Therapeutic Human Mesenchymal Stem/Stromal Cells in Microcarrier-Based Culture Systems.

    Fernandes-Platzgummer, Ana; Carmelo, Joana G; da Silva, Cláudia Lobato; Cabral, Joaquim M S

    2016-01-01

    The therapeutic potential of mesenchymal stem/stromal cells (MSC) has triggered the need for high cell doses in a vast number of clinical applications. This demand requires the development of good manufacturing practices (GMP)-compliant ex vivo expansion protocols that should be effective to deliver a robust and reproducible supply of clinical-grade cells in a safe and cost-effective manner. Controlled stirred-tank bioreactor systems under xenogeneic (xeno)-free culture conditions offer ideal settings to develop and optimize cell manufacturing to meet the standards and needs of human MSC for cellular therapies. Herein we describe two microcarrier-based stirred culture systems using spinner flasks and controlled stirred-tank bioreactors under xeno-free conditions for the efficient ex vivo expansion of human bone marrow and adipose tissue-derived MSC. PMID:27236684

  5. Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures

    Justesen, J; Dokkedahl, Karin Stenderup; Eriksen, E F;

    2002-01-01

    Osteoblasts and adipocytes share a common precursor cell in the bone marrow stroma, termed marrow stromal cell (MSC). As the volume of bone adipose tissue increases in vivo with age, we hypothesized that decreased bone formation observed during aging and in patients with osteoporosis (OP) is the...... result of enhanced adipogenesis and decreased osteoblastogenesis from the MSCs. Thus, cultures of MSCs were established from young donors (age 18-42, n = 34), elderly healthy donors (age 66-78, n = 20), and patients with OP (age 58-76, n = 15). Cells were cultured for 2 weeks in an adipogenic medium...... phosphatase (AP+), and adipocytic colonies containing adipocytes (Ad+) were quantitated. In addition, steady state mRNA levels of gene markers of adipocytic and osteoblastic phenotypes were determined using reverse-transcriptase polymerase chain reaction (RT-PCR). The adipogenic and osteogenic media induced...

  6. ULTRASONOGRAPHIC FEATURES OF CANINE GASTROINTESTINAL STROMAL TUMORS COMPARED TO OTHER GASTROINTESTINAL SPINDLE CELL TUMORS.

    Hobbs, Joshua; Sutherland-Smith, James; Penninck, Dominique; Jennings, Samuel; Barber, Lisa; Barton, Bruce

    2015-01-01

    Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of gastrointestinal spindle cell tumor recognized with the increasing use of immunohistochemistry. To our knowledge, no imaging features have been described in immunostochemically confirmed canine GISTs. The objective of this retrospective, cross-sectional study was to describe ultrasonographic features of canine GISTs compared with other spindle cell tumors. Thirty-seven dogs with an ultrasonographically visible gastrointestinal mass and a histopathologic diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining was performed for retrieved tissue samples to further differentiate the tumor type and each sample was interpreted by a single veterinary pathologist. Ultrasonographic features recorded examined included mass echogenicity, homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and loss of wall layering, location, size, vascularity, and evidence of perforation or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were significantly more likely to be associated (P < 0.03) with abdominal effusion than other tumor types. There was overlap between the anatomical locations of all tumors types with the exception of the cecum where all eight tumors identified were GISTs. Besides location, there were no unique ultrasound features of GISTs that would allow distinction from other gastrointestinal spindle cell tumors. Similar to previous studies, GISTs appeared to be the most common spindle cell tumor associated with the cecum in our sample of dogs. The high frequency of abdominal effusion with GIST's was of unknown etiology could possibly have been due to septic peritonitis. PMID:25846814

  7. Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells.

    Lo, Albert; Wang, Liang-Chuan S; Scholler, John; Monslow, James; Avery, Diana; Newick, Kheng; O'Brien, Shaun; Evans, Rebecca A; Bajor, David J; Clendenin, Cynthia; Durham, Amy C; Buza, Elizabeth L; Vonderheide, Robert H; June, Carl H; Albelda, Steven M; Puré, Ellen

    2015-07-15

    Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal cells (CASC) are a heterogeneous population that provides both negative and positive signals for tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker of a major subset of CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent negative prognostic factor for multiple types of human malignancies. Prior studies established that depletion of FAP(+) cells inhibits tumor growth by augmenting antitumor immunity. However, the potential for immune-independent effects on tumor growth have not been defined. Herein, we demonstrate that FAP(+) CASCs are required for maintenance of the provisional tumor stroma because depletion of these cells, by adoptive transfer of FAP-targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also decreased tumor vascular density and restrained growth of desmoplastic human lung cancer xenografts and syngeneic murine pancreatic cancers in an immune-independent fashion. Adoptive transfer of FAP-CAR T cells also restrained autochthonous pancreatic cancer growth. These data distinguish the function of FAP(+) CASCs from other CASC subsets and provide support for further development of FAP(+) stromal cell-targeted therapies for the treatment of solid tumors. PMID:25979873

  8. Age-associated vascular inflammation promotes monocytosis during atherogenesis.

    Du, Wei; Wong, Christine; Song, Yang; Shen, Hua; Mori, Daniel; Rotllan, Noemi; Price, Nathan; Dobrian, Anca D; Meng, Hailong; Kleinstein, Steven H; Fernandez-Hernando, Carlos; Goldstein, Daniel R

    2016-08-01

    Aging leads to a proinflammatory state within the vasculature without disease, yet whether this inflammatory state occurs during atherogenesis remains unclear. Here, we examined how aging impacts atherosclerosis using Ldlr(-/-) mice, an established murine model of atherosclerosis. We found that aged atherosclerotic Ldlr(-/-) mice exhibited enhanced atherogenesis within the aorta. Aging also led to increased LDL levels, elevated blood pressure on a low-fat diet, and insulin resistance after a high-fat diet (HFD). On a HFD, aging increased a monocytosis in the peripheral blood and enhanced macrophage accumulation within the aorta. When we conducted bone marrow transplant experiments, we found that stromal factors contributed to age-enhanced atherosclerosis. To delineate these stromal factors, we determined that the vasculature exhibited an age-enhanced inflammatory response consisting of elevated production of CCL-2, osteopontin, and IL-6 during atherogenesis. In addition, in vitro cultures showed that aging enhanced the production of osteopontin by vascular smooth muscle cells. Functionally, aged atherosclerotic aortas displayed higher monocyte chemotaxis than young aortas. Hence, our study has revealed that aging induces metabolic dysfunction and enhances vascular inflammation to promote a peripheral monocytosis and macrophage accumulation within the atherosclerotic aorta. PMID:27135421

  9. Human pathological basis of blood vessels and stromal tissue for nanotechnology.

    Nishihara, Hiroshi

    2014-07-01

    The recent development of nanotechnology has already produced clinically applicable "nanodrugs," which are largely dependent on a novel concept for the drug delivery system. Thus the elucidation of local pharmacokinetics of nanodrugs is indispensable for the further development of nanomedicine; however, the detailed pathophysiology associated with nano-sized materials especially in pathologic lesions has not been well-described. In this review article, the microscopic appearance of vascular pericytes in addition to endothelial cells is discussed in the normal state and also in several pathological conditions which could be the major targets for nanomedicine. Moreover, the role of stromal tissue including myofibroblasts is also focused on, as well as inflammatory cells. Finally, the significance of disease-specific tissue structure in the establishment of personalized nanomedicine is discussed. PMID:24462455

  10. Mechanical homeostasis regulating adipose tissue volume

    Svedman Paul

    2007-09-01

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

  11. Adipocyte-Specific Mineralocorticoid Receptor Overexpression in Mice Is Associated With Metabolic Syndrome and Vascular Dysfunction: Role of Redox-Sensitive PKG-1 and Rho Kinase.

    Nguyen Dinh Cat, Aurelie; Antunes, Tayze T; Callera, Glaucia E; Sanchez, Ana; Tsiropoulou, Sofia; Dulak-Lis, Maria G; Anagnostopoulou, Aikaterini; He, Ying; Montezano, Augusto C; Jaisser, Frederic; Touyz, Rhian M

    2016-08-01

    Mineralocorticoid receptor (MR) expression is increased in adipose tissue from obese individuals and animals. We previously demonstrated that adipocyte-MR overexpression (Adipo-MROE) in mice is associated with metabolic changes. Whether adipocyte MR directly influences vascular function in these mice is unknown. We tested this hypothesis in resistant mesenteric arteries from Adipo-MROE mice using myography and in cultured adipocytes. Molecular mechanisms were probed in vessels/vascular smooth muscle cells and adipose tissue/adipocytes and focused on redox-sensitive pathways, Rho kinase activity, and protein kinase G type-1 (PKG-1) signaling. Adipo-MROE versus control-MR mice exhibited reduced vascular contractility, associated with increased generation of adipocyte-derived hydrogen peroxide, activation of vascular redox-sensitive PKG-1, and downregulation of Rho kinase activity. Associated with these vascular changes was increased elastin content in Adipo-MROE. Inhibition of PKG-1 with Rp-8-Br-PET-cGMPS normalized vascular contractility in Adipo-MROE. In the presence of adipocyte-conditioned culture medium, anticontractile effects of the adipose tissue were lost in Adipo-MROE mice but not in control-MR mice. In conclusion, adipocyte-MR upregulation leads to impaired contractility with preserved endothelial function and normal blood pressure. Increased elasticity may contribute to hypocontractility. We also identify functional cross talk between adipocyte MR and arteries and describe novel mechanisms involving redox-sensitive PKG-1 and Rho kinase. Our results suggest that adipose tissue from Adipo-MROE secrete vasoactive factors that preferentially influence vascular smooth muscle cells rather than endothelial cells. Our findings may be important in obesity/adiposity where adipocyte-MR expression/signaling is amplified and vascular risk increased. PMID:27207514

  12. Poikiloderma vasculare atrophicans

    Padmavathy L

    1994-01-01

    Full Text Available A 65 year old lady presented with generalised pruritus and discolouration of skin and mucous membranes of 5 years duration. The histopathology from the cutaneous lesions revealed features suggestive of poikiloderma vasculare atrophicans (PVA. Investigations did not reveal any underlying connective tissue disease,lymphoma or systemic disease. A diagnosis of idiopathic poikiloderma vasculare atrophicans was made.

  13. Poikiloderma vasculare atrophicans

    Padmavathy L; Prasad PVS; Prasanna K; Rao L

    1994-01-01

    A 65 year old lady presented with generalised pruritus and discolouration of skin and mucous membranes of 5 years duration. The histopathology from the cutaneous lesions revealed features suggestive of poikiloderma vasculare atrophicans (PVA). Investigations did not reveal any underlying connective tissue disease,lymphoma or systemic disease. A diagnosis of idiopathic poikiloderma vasculare atrophicans was made.

  14. Obesity is associated with macrophage accumulation in adipose tissue

    Weisberg, Stuart P.; McCann, Daniel; Desai, Manisha; Rosenbaum, Michael; Leibel, Rudolph L.; Ferrante, Anthony W

    2003-01-01

    Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We fou...

  15. Decellularization of human stromal refractive lenticules for corneal tissue engineering.

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  16. Decellularization of human stromal refractive lenticules for corneal tissue engineering

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M.; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S.

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  17. Vascular grading of angiogenesis

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt; Bak, M; Vach, W; Rose, C

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  18. [Vascular factors in glaucoma].

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation. PMID:26597554

  19. Methods in Enzymology (MIE): Methods of Adipose Tissue Biology-: Chapter 7: Imaging of Adipose Tissue

    Berry, Ryan; Church, Christopher; Gericke, Martin T; Jeffery, Elise; Colman, Laura; Rodeheffer, Matthew S.

    2014-01-01

    Adipose tissue is an endocrine organ that specializes in lipid metabolism and is distributed throughout the body in distinct white adipose tissue (WAT) and brown adipose tissue (BAT) depots. These tissues have opposing roles in lipid metabolism with WAT storing excessive caloric intake in the form of lipid, and BAT burning lipid through non-shivering thermogenesis. As accumulation of lipid in mature adipocytes of WAT leads to obesity and increased risk of comorbidity (Pi-Sunyer et al., 1998),...

  20. Differential fatty acid profile in adipose and non-adipose tissues in obese mice

    Li, Mengting; Fu, Weisi; Li, Xiang-An

    2010-01-01

    Obesity is a metabolic disease characterized by chronic inflammation. Early studies indicated that adipose tissue from obese mice contains more saturated fatty acids and that the saturated fatty acids activate TLR4-mediated inflammatory signaling, which contributes to inflammation in adipose tissue. In this study, we determined fatty acid profile in non-adipose tissues from obese (db/db) mice and compared with that from lean mice. Unexpectedly, in contrast to a significant increase in saturat...

  1. Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity

    Pang, Can; Gao, Zhanguo; Yin, Jun; Zhang, Jin; Jia, Weiping; Ye, Jianping

    2008-01-01

    The biological role of macrophage infiltration into adipose tissue in obesity remains to be fully understood. We hypothesize that macrophages may act to stimulate angiogenesis in the adipose tissue. This possibility was examined by determining macrophage expression of angiogenic factor PDGF (platelet-derived growth factor) and regulation of tube formation of endothelial cells by PDGF. The data suggest that endothelial cell density was reduced in the adipose tissue of ob/ob mice. Expression of...

  2. In vitro differentiation of porcine aortic vascular precursor cells to endothelial and vascular smooth muscle cells.

    Zaniboni, Andrea; Bernardini, Chiara; Bertocchi, Martina; Zannoni, Augusta; Bianchi, Francesca; Avallone, Giancarlo; Mangano, Chiara; Sarli, Giuseppe; Calzà, Laura; Bacci, Maria Laura; Forni, Monica

    2015-09-01

    Recent findings suggest that progenitor and multipotent mesenchymal stromal cells (MSCs) are associated with vascular niches. Cells displaying mesenchymal properties and differentiating to whole components of a functional blood vessel, including endothelial and smooth muscle cells, can be defined as vascular stem cells (VSCs). Recently, we isolated a population of porcine aortic vascular precursor cells (pAVPCs), which have MSC- and pericyte-like properties. The aim of the present work was to investigate whether pAVPCs possess VSC-like properties and assess their differentiation potential toward endothelial and smooth muscle lineages. pAVPCs, maintained in a specific pericyte growth medium, were cultured in high-glucose DMEM + 10% FBS (long-term medium, LTM) or in human endothelial serum-free medium + 5% FBS and 50 ng/ml of hVEGF (endothelial differentiation medium, EDM). After 21 days of culture in LTM, pAVPCs showed an elongated fibroblast-like morphology, and they seem to organize in cord-like structures. qPCR analysis of smooth muscle markers [α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin (SMM) heavy chain] showed a significant increment of the transcripts, and immunofluorescence analysis confirmed the presence of α-SMA and SMM proteins. After 21 days of culture in EDM, pAVPCs displayed an endothelial cell-like morphology and revealed the upregulation of the expression of endothelial markers (CD31, vascular endothelial-cadherin, von Willebrand factor, and endothelial nitric oxide synthase) showing the CD31-typical pattern. In conclusion, pAVPCs could be defined as a VSC-like population considering that, if they are maintained in a specific pericyte medium, they express MSC markers, and they have, in addition to the classical mesenchymal trilineage differentiation potential, the capacity to differentiate in vitro toward the smooth muscle and the endothelial cell phenotypes. PMID:26135800

  3. Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets.

    Gruia, Alexandra T; Suciu, Maria; Barbu-Tudoran, Lucian; Azghadi, Seyed Mohammad Reza; Cristea, Mirabela I; Nica, Dragos V; Vaduva, Adrian; Muntean, Danina; Mic, Ani Aurora; Mic, Felix A

    2016-04-01

    Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332160

  4. [Therapeutic potential of human mesenchymal stromal cells secreted components: a problem with standartization].

    Sagaradze, G D; Grigorieva, O A; Efimenko, A Yu; Chaplenko, A A; Suslina, S N; Sysoeva, V Yu; Kalinina, N I; Akopyan, Zh A; Tkachuk, V A

    2015-01-01

    Regenerative medicine approaches, such as replacement of damaged tissue by ex vivo manufactured constructions or stimulation of endogenous reparative and regenerative processes to treat different diseases, are actively developing. One of the major tools for regenerative medicine are stem and progenitor cells, including multipotent mesenchymal stem/stromal cells (MSC). Because the paracrine action of bioactive factors secreted by MSC is considered as a main mechanism underlying MSC regenerative effects, application of MSC extracellular secreted products could be a promising approach to stimulate tissue regeneration; it also has some advantages compared to the injection of the cells themselves. However, because of the complexity of composition and multiplicity of mechanisms of action distinguished the medicinal products based on bioactive factors secreted by human MSC from the most of pharmaceuticals, it is important to develop the approaches to their standardization and quality control. In the current study, based on the literature data and guidelines as well as on our own experimental results, we provided rationalization for nomenclature and methods of quality control for the complex of extracellular products secreted by human adipose-derived MSC on key indicators, such as "Identification", "Specific activity" and "Biological safety". Developed approaches were tested on the samples of conditioned media contained products secreted by MSC isolated from subcutaneous adipose tissue of 30 donors. This strategy for the standardization of innovative medicinal products and biomaterials based on the bioactive extracellular factors secreted by human MSC could be applicable for a wide range of bioactive complex products, produced using the different types of stem and progenitor cells. PMID:26716748

  5. Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

    Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, 'big' insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established

  6. Mesenchymal Stem/Stromal Cells in Stromal Evolution and Cancer Progression

    Francesca Cammarota; Laukkanen, Mikko O

    2016-01-01

    The study of cancer biology has mainly focused on malignant epithelial cancer cells, although tumors also contain a stromal compartment, which is composed of stem cells, tumor-associated fibroblasts (TAFs), endothelial cells, immune cells, adipocytes, cytokines, and various types of macromolecules comprising the extracellular matrix (ECM). The tumor stroma develops gradually in response to the needs of epithelial cancer cells during malignant progression initiating from increased local vascul...

  7. [Gastrointestinal stromal tumors. A case of small intestine stromal tumor (SIST) with an uncertain biological aspect].

    Quaglino, F; Borello, M; Cumbo, P; Pietribiasi, F; Poma, A; Seglie, E; Do, D

    2000-05-01

    Tumors of the small intestine are relatively rare. The diagnosis is difficult to establish because the symptoms are vague and non-specific. Although the small intestine constitutes 75% of the length and over 90% of the mucosal surface area of the gastrointestinal tract, only 1 to 2% of gastrointestinal malignancies occur in this segment. Metastases are usually present at the time of diagnosis. The outcome of these patients can be improved if the possibility of a malignant small bowel tumor is considered in all cases of unexplained abdominal pain or gastrointestinal bleeding, especially in younger age. Malignant tumors occur with increasing frequency in distal small bowel with a preponderance of malignant lesions in the ileum compared with the jejunum and the duodenum. Adenocarcinoma is the most common tumor of the primary malignant small bowel tumors, followed by carcinoid, lymphoma and leiomyosarcoma. Mesenchymal tumors of the gastrointestinal tract, traditionally regarded as smooth muscle tumors, have demonstrated different cellular differentiations based on immunohistochemical and ultrastructural features. Therefore the terms leiomyoma and leiomyosarcoma have been replaced by a more encompassing term, gastrointestinal stromal tumor (GIST). The majority of GISTs occurs in the stomach; stromal tumors involving the small intestine (SISTs) are far less common but seem to have greater malignant potential. The clinical a case of a small intestinal stromal tumor (SIST), localised in the jejunum and characterised by an uncertain histological aspect, is presented and a review of the literature is made. PMID:10953571

  8. Potential of Adipose-derived stem cells in muscular regenerative therapies

    Sonia Forcales

    2015-07-01

    Full Text Available Regenerative capacity of skeletal muscles resides in satellite cells, a self-renewing population of muscle cells. Several studies are investigating epigenetic mechanisms that control myogenic proliferation and differentiation to find new approaches that could boost regeneration of endogenous myogenic progenitor populations. In recent years, a lot of effort has been applied to purify, expand and manipulate adult stem cells from muscle tissue. However, this population of endogenous myogenic progenitors in adults is limited and their access is difficult and invasive. Therefore, other sources of stem cells with potential to regenerate muscles need to be examined. An excellent candidate could be a population of adult stromal cells within fat characterized by mesenchymal properties, which have been termed adipose-derived stem cells (ASCs. These progenitor adult stem cells have been successfully differentiated in vitro to osteogenic, chondrogenic, neurogenic and myogenic lineages. Autologous adipose-derived stem cells are multipotent and can be harvested with low morbidity; thus, they hold promise for a range of therapeutic applications. This review will discuss the use of ASCs in muscle regenerative approaches.

  9. Aetiological factors behind adipose tissue inflammation

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

    2013-01-01

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

  10. Pediatric vascular access

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  11. Pediatric vascular access

    Donaldson, James S. [Northwestern University, Feinberg School of Medicine, Department of Medical Imaging, Children' s Memorial Hospital, Chicago, IL (United States)

    2006-05-15

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  12. Influencing Factors of Thermogenic Adipose Tissue Activity

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called “brite” or “beig...

  13. Injectable Biomaterials for Adipose Tissue Engineering

    Young, D. Adam; Christman, Karen 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 classifi...

  14. Obesity and adipose tissue endocrine function

    Joshi, Anuradha Rajiv

    2013-01-01

    Many studies have profoundly changed the concept of adipose tissue from being an energy depot to an active endocrine organ. Adipose tissue secretes bioactive peptides, termed as ‘adipokines’.They act through autocrine, paracrine and endocrine pathways. In obesity, increased production of most adipokines affects multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis. Increased activity of the tumor n...

  15. Mechanical homeostasis regulating adipose tissue volume

    Svedman Paul

    2007-01-01

    Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by str...

  16. Hypertension in Metabolic Syndrome: Vascular Pathophysiology

    Yolanda Mendizábal

    2013-01-01

    Full Text Available Metabolic syndrome is a cluster of metabolic and cardiovascular symptoms: insulin resistance (IR, obesity, dyslipemia. Hypertension and vascular disorders are central to this syndrome. After a brief historical review, we discuss the role of sympathetic tone. Subsequently, we examine the link between endothelial dysfunction and IR. NO is involved in the insulin-elicited capillary vasodilatation. The insulin-signaling pathways causing NO release are different to the classical. There is a vasodilatory pathway with activation of NO synthase through Akt, and a vasoconstrictor pathway that involves the release of endothelin-1 via MAPK. IR is associated with an imbalance between both pathways in favour of the vasoconstrictor one. We also consider the link between hypertension and IR: the insulin hypothesis of hypertension. Next we discuss the importance of perivascular adipose tissue and the role of adipokines that possess vasoactive properties. Finally, animal models used in the study of vascular function of metabolic syndrome are reviewed. In particular, the Zucker fatty rat and the spontaneously hypertensive obese rat (SHROB. This one suffers macro- and microvascular malfunction due to a failure in the NO system and an abnormally high release of vasoconstrictor prostaglandins, all this alleviated with glitazones used for metabolic syndrome therapy.

  17. Ex vivo expansion of mesenchymal stromal cells.

    Bernardo, Maria Ester; Cometa, Angela Maria; Pagliara, Daria; Vinti, Luciana; Rossi, Francesca; Cristantielli, Rosaria; Palumbo, Giuseppe; Locatelli, Franco

    2011-03-01

    Mesenchymal stromal cells (MSCs) are adult multipotent cells that can be isolated from several human tissues. MSCs represent a novel and attractive tool in strategies of cellular therapy. For in vivo use, MSCs have to be ex vivo expanded in order to reach the numbers suitable for their clinical application. Despite being efficacious, the use of fetal calf serum for MSC ex vivo expansion for clinical purposes raises concerns related to immunization and transmission of zoonoses; the standardization of expansion methods, possibly devoid of animal components, such as those based on platelet lysate, are discussed in this paper. Moreover, this review focuses on the search of novel markers for the prospective identification/isolation of MSCs and on the potential risks connected with ex vivo expansion of MSCs, in particular that of their malignant transformation. Available tests to study the genetic stability of ex vivo expanded MSCs are also analyzed. PMID:21396595

  18. MSCT findings of gastrointerstinal stromal tumor

    Objective: To investigate the CT features of gastro-interstinal stromal tumors (GISTs) and the value of MSCT in the diagnosis of this disease. Methods: CT findings of 22 cases with pathologically proved GISTs were retrospectively analyzed. Results: The locations of primary tumor were at stomach (n=13), jejunum (n=5), rectum (n=1) and mesenterium (n=3), including benign lesions (n=4), borderline tumors (n=3), and malignant tumors (n=15). Necrosis in 12 malignant GISTs and hepatic metastases in 6 cases were found. Pancreas was involved in 3 cases and peripheral peritoneum was involved in 2 cases. Metastatic lymph node was found in 1 case. Conclusion: MSCT provides important and helpful information for localization and diagnosis of GISTs. (authors)

  19. Gastrointestinal Stromal Tumors of the Pancreas

    Muhammad Wasif Saif

    2010-07-01

    Full Text Available Dear Sir, We read with great interest the case report published by Padhi et al. in the 2010 May issue of JOP. J Pancreas (Online titled “Extragastrointestinal Stromal Tumor Arising in the Pancreas: A Case Report with a Review of the Literature” [1]. Extragastrointestinal stromal tumors arising in the pancreas are extremely rare. Only nine cases have been reported in the literature up to today including the one by Padhi et al. [1, 2, 3, 4, 5, 6, 7, 8, 9]. We here report another case, probably to be the 10th in medical literature of a pancreatic gastrointestinal stromal tumor (GIST patient with an aggressive outcome. Our patient is a 31-year-old male in his usual state of health until February 2009 when he began to experience abdominal pain and fatigue accompanied by a 4.5 kg weight loss. There was no history of pancreatitis or abdominal trauma. He had a small episode of hematemesis for which he had blood work performed including complete blood count that revealed hemoglobin of 4.6 g/dL (reference range: 14.0-18.0 g/dL. He was admitted to the hospital where received 5 units of packed red blood cells and he was subsequently evaluated with upper endoscopy. Upon the procedure a friable area of mucosa was identified on the duodenum of which no biopsy could be taken. After this finding he had a CT scan which showed a 5.1x4.2x5.6 cm hypervascular mass in the pancreatic head compressing the common bile duct with minimal dilatation. The mass was further characterized by MRI, in which a 5.0x4.3 soft tissue mass was invading the pancreatic head and duodenum, obstructing the common bile duct without pancreatic duct obstruction. On admission, his total bilirubin was 7.3 mg/dL (reference range: 0-1.20 mg/dL, alkaline phosphatase was 686 U/L (reference range: 30-130 U/L, CA 19-9 was 11 U/mL (reference range: 0-37 U/mL, and CEA was 0.9 ng/mL (reference range: 0-3.0 ng/mL. The patient underwent a pylorus-preserving pancreatoduodenectomy and the pathology

  20. Imaging of gastrointestinal stromal tumour (GIST)

    Lau, S. E-mail: laushunhk@yahoo.com.hk; Tam, K.F.; Kam, C.K.; Lui, C.Y.; Siu, C.W.; Lam, H.S.; Mak, K.L

    2004-06-01

    Gastrointestinal stromal tumour (GIST) represents the most common kind of mesenchymal tumour that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumour containing spindle cells (or less commonly epithelioid cells or rarely both) and showing CD117 (c-kit protein) positivity. Targeted molecular therapy of non-resectable GIST using imatinib, a specific tyrosine kinase receptor inhibitor, represents a real milestone in the management of solid malignancy. Imaging studies, both anatomical and functional, are playing an increasingly important role in management of patients with GIST. This review illustrates the radiological appearance of GISTs and the site-specific roles of each imaging tool. Clinical features and radiological differential diagnosis of GIST are also discussed.

  1. Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.

    Bourke, Anita Geraldine; Tiang, Stephen; Harvey, Nathan; McClure, Robert

    2015-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement. PMID:26475873

  2. Influencing Factors of Thermogenic Adipose Tissue Activity.

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called "brite" or "beige" adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID:26903879

  3. Determinants of Central Adiposity among Iranian Population

    Leila Azadbakht

    2013-03-01

    Full Text Available Background: Central obesity is one of the major public health problems. Recent studies have indicated that body fat distribution would be important in general health. Materials and Methods: The present study is a review of several studies which discuss the contributing factors of abdominal obesity, particulary in Iran. This study reviews 34 cross-sectional and interventional studies, which have been comducted during 1995-2012 and issued in English language. PubMed search engine and the related keywords were used to search the papers.Results: Breakfast skipping and also the sleep duration as well as the quality of diet are also associated with central adiposity. Dietary diversity score among Iranians can be related to abdominal adiposity. Fastfood consumption can increase the risk of central adiposity among young Iranian population. Red meat intake and food source of trans fat can increase the risk of central adiposity. Low quality diet with low amount of nutrients can increase the risk of central adiposity. Conclusion: Some behaviours such as sleep duration and eating breakfast can be associated with central adiposity among Iranians. Diet quality and dietary diversity score is also associated with this problem among Iranians.

  4. Upper gastrointestinal hemorrhage due to duodenal stromal tumor

    Parreira José Gustavo

    2003-01-01

    Full Text Available BACKGROUND: Gastrointestinal stromal tumor represents a rare neoplasm that originates in the muscular wall of the hollow viscera. AIM: To report gastrointestinal stromal tumor as a source of upper gastrointestinal bleeding, which required urgent surgical control. PATIENT/METHOD: A man with 61 years old was admitted to the emergency service sustaining hematemesis and melena. Endoscopy showed active bleeding from a tumor in the second portion of the duodenum, which was controlled by heater probe cauterization. Surgery was performed through a median laparotomy. A local resection of a 4 cm tumor in the second portion of the duodenum was carried out, together with a primary end-to-end anastomosis and a duodenal diverticulization. No complications happened during the post-operative period. Morphologic examination showed gastrointestinal stromal tumor with no atypical mitosis and a preserved capsule. CONCLUSION: Albeit not being common, gastrointestinal stromal tumors can represent a source of substantial gastrointestinal hemorrhage.

  5. Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance.

    Aleksandra Nowicka

    Full Text Available Adipose tissue contains a population of multipotent adipose stem cells (ASCs that form tumor stroma and can promote tumor progression. Given the high rate of ovarian cancer metastasis to the omental adipose, we hypothesized that omental-derived ASC may contribute to ovarian cancer growth and dissemination.We isolated ASCs from the omentum of three patients with ovarian cancer, with (O-ASC4, O-ASC5 and without (O-ASC1 omental metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells proliferation, chemoresistance and radiation resistance was evaluated using co-culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASCs and control cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to track in-vivo engraftment.O-ASCs significantly promoted in vitro proliferation, migration chemotherapy and radiation response of ovarian cancer cell lines. O-ASC4 had more marked effects on migration and chemotherapy response on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O-ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical clustering. Human O-ASCs were detected in the stroma of human ovarian cancer murine xenografts but not uninvolved ovaries.ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs isolates demonstrate heterogenous effects on ovarian cancer in-vitro.

  6. Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

    Maessen, Dionne E; Brouwers, Olaf; Gaens, Katrien H; Wouters, Kristiaan; Cleutjens, Jack P; Janssen, Ben J; Miyata, Toshio; Stehouwer, Coen D; Schalkwijk, Casper G

    2016-04-01

    Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. PMID:26718500

  7. Bone marrow stromal cell: mediated neuroprotection for spinal cord repair

    Ritfeld, Gaby Jane

    2014-01-01

    Currently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic factors, enabling neuroprotection/tissue sparing in a rat model of spinal cord injury. In this model system, bone marrow stromal cell-mediated tissue sparing leads to motor and sensory function impr...

  8. Regulation of Hematopoietic Stem Cells by Bone Marrow Stromal Cells

    Anthony, Bryan; Link, Daniel C.

    2013-01-01

    Hematopoietic stem cells (HSCs) reside in specialized microenvironments (niches) in the bone marrow. The stem cell niche is thought to provide signals that support key HSC properties, including self-renewal capacity and long-term multilineage repopulation ability. The stromal cells that comprise the stem cell niche and the signals that they generate that support HSC function are the subjects of intense investigation. Here we review the complex and diverse stromal cell populations that reside ...

  9. Small bowel stromal tumour revealed by a lower gastrointestinal bleeding

    Assamoi B. F. Kassi

    2016-04-01

    Full Text Available Small bowel stromal tumour must be systematically researched in the presence of obscure and persistent low gastrointestinal bleeding despite a normal endoscopic examination (OGDF and colonoscopy. Video capsule endoscopy is the best diagnosis examination; if it is not available a CT enterography could be useful. Surgical treatment is effective on localized and weak malignancy small bowel stromal tumours. [Int J Res Med Sci 2016; 4(4.000: 1248-1250

  10. Small bowel stromal tumour revealed by a lower gastrointestinal bleeding

    Assamoi B. F. Kassi; Lebeau, R; Y. S. Kacou; K. J. N'dah; Traore, M.

    2016-01-01

    Small bowel stromal tumour must be systematically researched in the presence of obscure and persistent low gastrointestinal bleeding despite a normal endoscopic examination (OGDF and colonoscopy). Video capsule endoscopy is the best diagnosis examination; if it is not available a CT enterography could be useful. Surgical treatment is effective on localized and weak malignancy small bowel stromal tumours. [Int J Res Med Sci 2016; 4(4.000): 1248-1250

  11. Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis

    Kramer, Klaus; Hasel, Cornelia; Aschoff, Andrik J; Henne-Bruns, Doris; Wuerl, Peter

    2007-01-01

    The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy reveale...

  12. Congenital Vascular Malformation

    ... clots, obstruction of major vessels, causing progressive limb asymmetry by overgrowth, and for cosmetic indications or because ... t he Vascular Disease Foundation (VDF) develops educational information and initiatives for patients, their families and friends, ...

  13. Vascular Access for Hemodialysis

    ... for short-term use. [ Top ] What is an arteriovenous fistula? An AV fistula is a connection, made by ... to remove and return blood during hemodialysis. An arteriovenous (AV) fistula is a connection, made by a vascular surgeon, ...

  14. Heart and vascular services

    ... Repair of aneurysms (dilated/enlarged portions) of the aorta and its branches Procedures may also be used ... Nutrition and lifestyle counseling, including smoking cessation and diabetes education Supervised exercise Alternative Names Circulatory system; Vascular ...

  15. Management of Vascular Malformations

    Sadanori Akita, MD, PhD

    2014-03-01

    Conclusions: Treatment of vascular malformations is an integral part of multidisciplinary approaches. Venous malformations are more frequent in combination surgery, and if there are fewer complications, the patients’ satisfaction increases.

  16. Vascular Effects of Histamine.

    Ebeigbe, Anthony B; Talabi, Olufunke O

    2014-01-01

    Four subtypes of receptors (H1, H2, H3 and H4) mediate the actions of histamine. In the vascular wall, the effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype located on presynaptic neurones. Alterations in vascular responses to histamine are associated with experimental as well as a human form of hypertension, suggesting a role for histanine in cardiovascular regulation. PMID:26196559

  17. Digital vascular imaging (DVI)

    Digitization of the video signals from an image intensifier/TV chain, followed by subtraction, contrast enchancement and reconversion to analogue signals, enables high quality angiographic images to be obtained from an intravenous injection of contrast medium. As the examination is basically noninvasive it can be used in outpatients. The possibilities of Digital Vascular Imaging are demonstrated by images obtained from the various vascular regions using a triple-mode 14 in. image intensifier with a Plumbicon. TV tube. (Auth.)

  18. Thrombolysis in vascular surgery

    Smith, Linn

    2015-01-01

    Background and aims: Thrombolysis is in common use in the treatment of acute forms of vascular disease. It may be used both systemically and locally, in the latter case through an endovascular approach, socalled catheter-directed thrombolysis. The aims of this thesis were to investigate how thrombolysis affects performance-related outcomes pertaining to vascular patency after thrombolysis, and how it affects patient safety and the development of complications. Metho...

  19. Comparative immunophenotyping of equine multipotent mesenchymal stromal cells: an approach toward a standardized definition.

    Paebst, Felicitas; Piehler, Daniel; Brehm, Walter; Heller, Sandra; Schroeck, Carmen; Tárnok, Attila; Burk, Janina

    2014-08-01

    Horses are an approved large animal model for therapies of the musculoskeletal system. Especially for tendon disease where cell-based therapy is commonly used in equine patients, the translation of achieved results to human medicine would be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells (MSCs) remains the last obstacle to meet the criteria of the International Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34, CD 45, CD 79α, and MHC II in equine MSCs from adipose tissue, bone marrow, umbilical cord blood, umbilical cord tissue, and tendon tissue was analyzed using flow cytometry. Isolated cells from the different sources and donors varied in their expression pattern of MSC-defining antigens. In particular, CD 90 and 105 showed most heterogeneity. However, cells from all samples were robustly positive for CD 29 and CD 44, while being mostly negative for CD 73 and the exclusion markers CD 14, CD 34, CD 45, CD 79α and MHC II. Furthermore, it was evident that enzymes used for cell detachment after in vitro-culture affected the detection of antigen expression. These results emphasize the need of standardization of MSC isolation, culturing, and harvesting techniques. As the equine MSCs did not meet all criteria the ISCT defined for human MSCs, further investigations for a better characterization of the cell type should be conducted. PMID:24894974

  20. Synchronous Acromegaly and Gastrointestinal Stromal Tumor: A Case Report

    Hüsniye Başer

    2014-06-01

    Full Text Available Acromegaly is a rare endocrine disorder characterized by the manifestations of sustained hypersecretion of growth hormone and concomitant elevations in circulating concentrations of insulin-like growth factor-1. It has been reported that patients with acromegaly are at the increased risk of developing malignant tumors, particularly colorectal cancer. Gastrointestinal stromal tumors are mesenchymal tumors of the digestive tract. An association between gastrointestinal stromal tumors and insulin-like growth factor system has been reported. Here, we report a patient diagnosed with synchronous acromegaly and gastrointestinal stromal tumor. A 59-year-old man with iron deficiency anemia presented with enlarged hands, coarse facial feature and several skin tags. Thyroid function tests were within normal range. Growth hormone was 5.14 ng/mL, insulin-like growth factor-1 was 820 ng/mL, and no growth hormone suppression was observed on 75g oral glucose tolerance test. Pituitary magnetic resonance imaging revealed microadenoma, and the patient was diagnosed with acromegaly. Upper gastrointestinal tract endoscopy revealed an ulcerovegetan mass in the duodenum and the results of the histopathologcal analysis was consistent with gastrointestinal stromal tumor. The association of synchronous and asynchronous gastrointestinal stromal tumors with other malignancies have been reported. The most common accompanying neoplasms are colorectal and gastric adenocarcinomas, as well as pancreatic tumors. However, in the literature, the number of reported cases of synchronous acromegaly and gastrointestinal stromal tumor are limited, and there are no sufficient data on this association. Turk Jem 2014; 2: 52-55

  1. [Zaidemberg's vascularized radial graft].

    Saint-Cast, Y

    2010-12-01

    In 1991, Carlos Zaidemberg described a new technique to repair scaphoid non-unions with a vascularized bone graft harvested from the radial styloid process. An anatomic study based on 30 dissections after colorized latex injection established the constancy of the radial styloid process's artery, while showing that its origin, course and length were subject to variations. In a retrospective series of 38 cases over a period of 10 years, the vascularized bone graft was indicated for: (1) scaphoid non-union with the presence of avascular changes of the proximal fragment (23 cases); (2) failed prior reconstruction with bone graft and internal fixation (nine cases); (3) degenerative styloid-scaphoid arthritis (three cases); (4) fracture on Preiser dystrophy (three cases). The five steps of the simplified operative technique without dissection of the vascular pedicle include: (1) longitudinal dorso-radial approach, identification of the periosteal portion of the radial styloid process artery; (2) incision of the first and second compartments, longitudinal arthrotomy under the second compartment; (3) styloidectomy and transversal resection of the scaphoid non-union and sclerotic bone; (4) elevation of the vascularized bone graft; (5) transversal and radial insertion of the vascularized bone graft, osteosynthesis by two or three K-wire touching the scaphoid's radial edge. Scaphoid union was obtained in 33 cases out of 38. The only postoperative complications were two transient radial paresthesia. The standardized surgical procedure using vascularized bone graft harvested from the radial styloid process provides an efficient scaphoid reconstruction. PMID:21087882

  2. Beta3 adrenergic receptor is involved in vascular injury in deoxycorticosterone acetate-salt hypertensive mice.

    Sheng, Li-Juan; Ruan, Cheng-Chao; Ma, Yu; Chen, Dong-Rui; Kong, Ling-Ran; Zhu, Ding-Liang; Gao, Ping-Jin

    2016-03-01

    Beta3 adrenergic receptor (ADRB3) mediates vessel relaxation in the endothelium while it modulates lipolysis in the adipose tissue. However, the function and regulation mechanism of ADRB3 in the perivascular adipose tissue (PVAT), especially in hypertension, is still unclear. We show that ADRB3 protein is upregulated in the PVAT of deoxycorticosterone acetate-salt (DOCA-salt) hypertensive mice, with the characteristics of PVAT browning and increased uncoupling protein 1 (UCP1) expression. Inhibition of ADRB3 with selective antagonist SR59230A caused serious vascular injury in vivo, even though UCP1 expression was downregulated. ADRB3 protein was regulated by let-7b, which was decreased in the PVAT of the DOCA-salt group. These data reveal that ADRB3 in PVAT contributes to vascular function in the progression of hypertension. PMID:26910302

  3. A 3-month age difference profoundly alters the primary rat stromal vascular fraction phenotype

    Quaade, Marlene Louise; Jensen, Charlotte Harken; Andersen, Ditte Caroline;

    2016-01-01

    such as age is demanded. Here we report that even a short age difference has an impact on the phenotype of primary SVF cells. We observed that a 3-month difference in relatively young adult rats affects the expression pattern of several mesenchymal stem cell markers in their primary SVF. The younger...

  4. 脂肪干细胞表型和标记物的研究进展%A review on phenotype and markers of adipose-derived stem cells

    陈犹白; 陈聪慧(综述); Qixu Zhang; 韩岩(审校)

    2016-01-01

    No consensus has been made so far on the specific markers of adipose-derived stem cells (ASCs) due to the differences of fat donor,micro-environment between in vivo and in vitro,cell passages and lack of standard of harvest,isolation,culture,et al.We reviewed all markers of ASCs and found that most positive markers are stromal cells and mesenchymal stem cells markers, while most negative markers were hematopoietic cells markers.The controversial markers of ASCs were basically bone marrow stem cells (BMSCs),vascular endothelial cells and pericytes markers. In vivo, fresh-isolated ASCs and ASCs from initial passages of in vitro expansion were CD34+, however the expression of CD34 was decreasing with long-term expansion in vitro and ifnally vanish. This was the reason of controversy on CD34 expression from literatures and the evidence that ASCs have different phenotypes in vivo and in vitro.Furthermore,stemness markers like Stro-1 were important and promising in identifying ASCs, however further studies are needed to determine their role in ASCs identiifcation. According to the phenotypic differences between Stromal vascular fraction (SVF) cells and ASCs subpopulations,we speculated that ASCs in vivo may origin from BMSCs,pericytes or ifbroblasts. We compared the phenotypes of ASCs with BMSCs and found that ASCs are CD36+/CD49d+/ CD48f-/CD104-, while BMSCs were the opposite,which could be used to identify ASCs from BMSCs.Finally,we introduced the experience of Tissue Regeneration and Molecular Cell Engineering Lab, Department of Plastic Surgery, MD Anderson Cancer Center and predicted the future research interests of ASCs phenotypes and markers based on our experience and current issues.%由于脂肪供体、提取方法、分离、培养、体内外微环境、鉴定时的细胞代数和检测方法等诸多因素的差异,迄今为止尚未发现脂肪干细胞(adipose-derived stem cell,ASCs)的特异性标记物。本文总结了所有ASCs的相关标记物

  5. MMP13 as a stromal mediator in controlling persistent angiogenesis in skin carcinoma.

    Lederle, Wiltrud; Hartenstein, Bettina; Meides, Alice; Kunzelmann, Heike; Werb, Zena; Angel, Peter; Mueller, Margareta M

    2010-07-01

    Matrix metalloproteinases (MMPs) such as MMP13 promote tumour growth and progression by mediating extracellular matrix (ECM) reorganization and regulating the biological activity of cytokines. Using Mmp13-/- mice, we demonstrate an essential role of this single collagenase for highly malignant and invasive growth in skin squamous cell carcinoma (SCC). Lack of host MMP13 strongly impaired tumour growth of malignant SCC cells, leading to small, mostly avascular cysts. While initial stromal activation in tumour transplants of Mmp13+/+ and Mmp13-/- animals was similar, MMP13 was essential for maintenance of angiogenesis and for invasion. MMP13 was induced in fibroblasts of the wild-type animals at the onset of invasion and correlated with a strong increase in vascular endothelial growth factor (VEGF) protein and its association with vascular endothelial growth factor receptor-2 on endothelial cells in invasive areas. In contrast, VEGF protein in the stroma was barely detectable and tumour invasion was downregulated in Mmp13-/- animals, despite ongoing VEGF messenger RNA expression. Taken together with in vitro data showing the release of VEGF from the ECM by MMP13 expressing fibroblasts, these data strongly suggest a crucial role of MMP13 in promoting angiogenesis via releasing VEGF from the ECM and thus allowing the invasive growth of the SCC cells. PMID:19892798

  6. The oncometabolite R-2-hydroxyglutarate activates NF-κB-dependent tumor-promoting stromal niche for acute myeloid leukemia cells.

    Chen, Jing-Yi; Lai, You-Syuan; Tsai, Hui-Jen; Kuo, Cheng-Chin; Yen, B Linju; Yeh, Su-Peng; Sun, H Sunny; Hung, Wen-Chun

    2016-01-01

    Mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 in acute myeloid leukemia (AML) cells produce the oncometabolite R-2-hydroxyglutarate (R-2HG) to induce epigenetic alteration and block hematopoietic differentiation. However, the effect of R-2HG released by IDH-mutated AML cells on the bone marrow microenvironment is unclear. Here, we report that R-2HG induces IκB kinase-independent activation of NF-κB in bone marrow stromal cells. R-2HG acts via a reactive oxygen species/extracellular signal-regulated kinase (ERK)-dependent pathway to phosphorylate NF-κB on the Thr254 residue. This phosphorylation enhances the interaction of NF-κB and the peptidyl-prolyl cis-trans isomerase PIN1 and increases the protein stability and transcriptional activity of NF-κB. As a consequence, R-2HG enhances NF-κB-dependent expression of cytokines including IL-6, IL-8 and complement 5a to stimulate proliferation of AML cells. In addition, R-2HG also upregulates vascular endothelial adhesion molecule 1 and CXCR4 in stromal cells to enhance the contact between AML and stromal cells and attenuates chemotherapy-induced apoptosis. More importantly, we validated the R-2HG-activated gene signature in the primary bone marrow stromal cells isolated from IDH-mutated AML patients. Collectively, our results suggest that AML cell-derived R-2HG may be helpful for the establishment of a supportive bone marrow stromal niche to promote AML progression via paracrine stimulation. PMID:27577048

  7. Antioxidants and vascular health.

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies. PMID:26585821

  8. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling

    Dmitry A. Chistiakov

    2015-01-01

    Full Text Available A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs and endothelial cells (ECs. These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles.

  9. Advanced liposuction technologies and their potential application in the isolation of adipose-derived stem cells%现代吸脂技术采集脂肪混合物在脂肪干细胞制备领域中的应用

    付寅生; 张怡

    2014-01-01

    BACKGROUND:Currently, cosmetic liposuction has developed rapidly, but the liposuction for the isolation of adipose-derived stem cells has not been reported. OBJECTIVE:By evaluating the quantity and viability of stromal vascular fraction, adipocytes and adipose-derived stem cells obtained from different types of liposuctions, to find the advanced liposuction procedures that are most suitable for use in preparation, preservation and clinical application of adipose-derived stem cells. METHODS:Authors retrieved PubMed database, NIH clinical trial databaseand CNKI ful text database for relevant articles using the key words of“adipose-derived stem cells, ADSCs, liposuction, SAL, UAL, PAL, WAL”in English and Chinese, respectively. After eliminating the objective-independent articles and repeating reviews, 50 papers were included for further analysis. RESULTS AND CONCLUSION:Suction-assisted liposuction (SAL), ultrasound-assisted liposuction (UAL), power-assisted liposuction (PAL) and water-assisted liposuction (WAL) are four major types of fat-harvesting technologies that can possibly be applied for adipose-derived stem cells isolation. Accumulative evidence suggests that these advanced liposuctions can obtain high quality of adipose tissue/cells, which are good enough for autologous fat grafting. Adipose-derived stem cells that are isolated from lipoaspirate by WAL, SAL and UAL, can be used as autologous cel-assisted lipotransfer and regenerative therapy. In summary, although each of these four types of liposuction technologies has its own advantages and is feasible to be used as autologous fat grafting, systematic comparative studies for viability, chromosome stability and differentiation potentials of adipose-derived stem cells isolated using each col ecting method are necessary in order to confirm the future perspectives in adipose-derived stem cells isolation, banking and regenerative repair.%背景:目前用于整容的吸脂术发展很快,但为了脂肪

  10. Visceral adiposity, insulin resistance and cancer risk

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  11. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    Andrew A. Bremer

    2013-01-01

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

  12. Carotenoids in Adipose Tissue Biology and Obesity.

    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. PMID:27485231

  13. Brown Adipose Tissue Growth and Development

    Michael E. Symonds

    2013-01-01

    Full Text Available Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  14. The role of complement system in adipose tissue-related inflammation.

    Vlaicu, Sonia I; Tatomir, Alexandru; Boodhoo, Dallas; Vesa, Stefan; Mircea, Petru A; Rus, Horea

    2016-06-01

    As the common factor linking adipose tissue to the metabolic context of obesity, insulin resistance and atherosclerosis are associated with a low-grade chronic inflammatory status, to which the complement system is an important contributor. Adipose tissue synthesizes complement proteins and is a target of complement activation. C3a-desArg/acylation-stimulating protein stimulates lipogenesis and affects lipid metabolism. The C3a receptor and C5aR are involved in the development of adipocytes' insulin resistance through macrophage infiltration and the activation of adipose tissue. The terminal complement pathway has been found to be instrumental in promoting hyperglycemia-associated tissue damage, which is characteristic of the major vascular complications of diabetes mellitus and diabetic ketoacidosis. As a mediator of the effects of the terminal complement complex C5b-9, RGC-32 has an impact on energy expenditure as well as lipid and glucose metabolic homeostasis. All of this evidence, taken together, indicates an important role for complement activation in metabolic diseases. PMID:26754764

  15. Effects of fetal and neonatal exposure to nicotine on blood pressure and perivascular adipose tissue function in adult life.

    Gao, Yu-Jing; Holloway, Alison C; Su, Li-Ying; Takemori, Kumiko; Lu, Chao; Lee, Robert M K W

    2008-08-20

    In Wistar rats, maternal exposure to nicotine was shown to impair the inhibitory function of perivascular adipose tissue on vascular contractility in the aorta of the offspring. It is not known whether an impairment of perivascular adipose tissue function occurs in smaller arteries, and whether the control of blood pressure is affected. Here we studied the blood pressure effects and the alteration of perivascular adipose tissue function in mesenteric arteries of the offspring born to Wistar-Kyoto rat (WKY) dams exposed to nicotine. Nulliparous female WKY rats were given either nicotine bitartrate (1 mg/kg/day) or saline (vehicle) by subcutaneous injection 2 weeks prior to mating, during pregnancy and until weaning. Blood pressure of the offspring and functional studies with mesenteric arteries were conducted. Tissue samples (thoracic aorta, mesenteric arteries, and kidneys) were collected for morphological and immunohistochemical examinations. Blood pressure increased from 14 weeks of age onwards in the offspring born to nicotine-exposed dams. Nicotine-exposed offspring showed a significant increase in the number of brown adipocytes in aortic perivascular adipose tissue relative to control offspring. In mesenteric arteries from control offspring, contractile responses induced by phenylephrine, serotonin, and 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F(2)alpha (U44619) were significantly attenuated in the presence of perivascular adipose tissue, an effect not observed in the nicotine-exposed tissues. Endothelium-dependent relaxation responses to carbachol, kidney weight, the total number of nephrons and glomerulus' size were comparable in nicotine and saline groups. We conclude that fetal and neonatal exposure to nicotine caused blood pressure elevation. Alterations in perivascular adipose tissue composition and modulatory function are some of the mechanisms associated with this blood pressure increase. PMID:18647709

  16. Adipose tissue plasticity from WAT to BAT and in between

    Lee, Yun-Hee; Mottillo, Emilio P.; Granneman, James G.

    2013-01-01

    Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticit...

  17. CT diagnosis of gastric stromal tumors

    Objective: To investigate the CT findings of gastric stromal tumors(GST) of the stomach. Methods: We retrospectively reviewed the CT imaging of 16 cases of GST confirmed operatively and pathologically, The gross pathologic findings of the tumors were compared with the manifestations of CT imagings. Results: In 17 cases of GST, 7 cases originated from submucous, 2 cases from muscular layer and 7 cases from Serosa Layers. among of which, 9 cases were low grade malignant, 7 cases were high grade. 16 cases of GST showed as exogenous or endogenous mass of 3-30 cm in greatest diameter, 3 cases with greatest diameter less than 5 cm and 13 of them with over 5 cm. The tumors were cystic-solid with inhomogenous attenuation, the solid potion of tumors enhanced lightly to moderately, Punctate calcification was seen in 3 GST. There were central low attenuating areas in the masses as well as peripheral enhancement in seven cases high-grade GST. Pathologic findings demonstrated that solid portions composed of spindle and(or) epithelioid cells. Conclusion: CT study is helpful for locating the tumor and observation of the relationship of the tumor and surrounding structures, The presence of ulcer, metastasis and the size of the tumor can predict the grade of GST. (authors)

  18. Targeted therapy of gastrointestinal stromal tumours.

    Jakhetiya, Ashish; Garg, Pankaj Kumar; Prakash, Gaurav; Sharma, Jyoti; Pandey, Rambha; Pandey, Durgatosh

    2016-05-27

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs. PMID:27231512

  19. Angiographic findings of gastrointestinal stromal tumor

    Song-Hua Fang; Dan-Jun Dong; Shi-Zheng Zhang; Mei Jin

    2004-01-01

    AIM: To discuss the angiographic features of gastrointestinal stromal tumor (GIST) and to evaluate their diagnostic role.METHODS:Twelve patients with pathologically proved GIST underwent angiography (DSA)1 wk before operation,using Puck and digital subtraction DSA.The origin,size,morphology and angiographic appearance of the lesions were reviewed.RESULTS:Two tumors arose from stomach,8 from jejunum,and 2 from ileum.Seven cases were benign and 5 were malignant.Obviously thickened supplying arteries were detected in 8 tumors,and early-developed veins were found in 3.Two types of angiographic changes of GIST were observed.Four cases had twisted irregular neoplastic vessels with partially coarse and indistinct margins,which were all malignant.Eight cases had ball-like neoplastic vessels with uniform tumor staining,of which 7 were benign and 1 was malignant.CONCLUSION:Angiography facilitates localization and diagnosis of GIST,helps define their size,range and location,and is especially valuable to patients suffering from melena with unknown reasons.

  20. Gastrointestinal Stromal Tumors in the Rectum

    Hongwei Lin; Yongfu Shao; Dongkui Xu; Dongbing Zhao; Haizeng Zhang; Tiecheng Wu

    2005-01-01

    OBJECTIVE To investigate the clinical and pathologic features of rectal gastrointestinal stromal tumors (GIST) and to evaluate their reasonable management.METHODS The clinical and pathological data for 19 patients with rectal GIST over the past 19 years were studied retrospectively.RESULTS The diagnosis of the 19 cases was identified by surgery and pathology. All the rectal GISTs were spindle cell type with immunohistohemical analysis showing positive reactivity for CD117 (100%) and CD34 (73.7%). There were 4 cases of high risk, 3 cases of intermediate risk, 5 cases of low risk and 7 cases of very low risk of aggressive behavior in this study.CONCLUSION Rectal GIST, without specific symptoms in the early stage, has a low incidence and usually shows low risk of aggressive behavior. It is difficult to produce an accurate pathological diagnosis before operation and it is difficult to decide whether to save the sphincter before or during operation. Reasonable initial treatment includes trans-anal local resection as the best recommend management of low risk submucosal rectal GIST (<3.0 cm).

  1. Tumoral pseudoangiomatous stromal hyperplasia of the breast.

    Wieman, Stephanie M; Landercasper, Jeffrey; Johnson, Jeanne M; Ellis, Richard L; Wester, Susan M; Lambert, Pamela J; Ross, Lauren A

    2008-12-01

    Tumoral pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferative disease of the breast. The majority of the literature reports of PASH have not contained detailed descriptions of the imaging characteristics of PASH. A 10-year retrospective study of patients with tumoral PASH and a 20-year Ovid MEDLINE search were performed to determine whether specific imaging and needle biopsy results could characterize PASH preoperatively. We identified 22 patients with tumoral PASH. Seventeen (77%) of 22 women had a palpable lump and 14 (72%) of 21 had a density on mammography. Ultrasound (US) findings included mixed or hypoechoic echogenicity in 83 per cent and ill-defined borders in 62 per cent. Eight (36%) patients had lesions with a Breast Imaging Reporting and Data System (BI-RADS) classification of 4 or 5. The sensitivity of preoperative core needle biopsy (CNB) to identify PASH was 83 per cent. A review of the literature revealed that 90 per cent of patients with PASH had some malignant imaging characteristics and 95 per cent had a mass on mammography. The imaging characteristics of PASH exhibited marked variability. Excision of PASH after CNB may be considered for patients with symptoms, enlarging lesions, or lesions classified as BI-RADS 4 or 5. PASH diagnosed by CNB allows selected patients to avoid excision. PMID:19097540

  2. Drug repurposing for gastrointestinal stromal tumor.

    Pessetto, Ziyan Y; Weir, Scott J; Sethi, Geetika; Broward, Melinda A; Godwin, Andrew K

    2013-07-01

    Despite significant treatment advances over the past decade, metastatic gastrointestinal stromal tumor (GIST) remains largely incurable. Rare diseases, such as GIST, individually affect small groups of patients but collectively are estimated to affect 25 to 30 million people in the United States alone. Given the costs associated with the discovery, development, and registration of new drugs, orphan diseases such as GIST are often not pursued by mainstream pharmaceutical companies. As a result, "drug repurposing" or "repositioning," has emerged as an alternative to the traditional drug development process. In this study, we screened 796 U.S. Food and Drug Administration (FDA)-approved drugs and found that two of these compounds, auranofin (Ridaura) and fludarabine phosphate, effectively and selectively inhibited the proliferation of GISTs, including imatinib-resistant cells. One of the most notable drug hits, auranofin, an oral, gold-containing agent approved by the FDA in 1985 for the treatment of rheumatoid arthritis, was found to inhibit thioredoxin reductase activity and induce reactive oxygen species (ROS) production, leading to dramatic inhibition of GIST cell growth and viability. Importantly, the anticancer activity associated with auranofin was independent of imatinib-resistant status, but was closely related to the endogenous and inducible levels of ROS. Coupled with the fact that auranofin has an established safety profile in patients, these findings suggest for the first time that auranofin may have clinical benefit for patients with GIST, particularly in those suffering from imatinib-resistant and recurrent forms of this disease. PMID:23657945

  3. Gastrointestinal Stromal Tumors: Epidemiology and Treatment Outcomes

    Peyvandi H

    2009-08-01

    Full Text Available Introduction: Numerous studies have investigated the prevalence, incidence and clinical manifestations of gastrointestinal stromal tumors (GISTs. However, little is known about GISTs in Iran. This pioneer st udy focuses on descri ption of 36 patients with GISTs in Iran. Methods: A database was created for 36 patie nts suffering from GIST who were treated in Loghman Medical Center and Tehran Cancer Institute in Tehran, Iran. Information on age, sex, clinical mani festations, treatment and outcomes were recorded and analyzed using SPSS version 13. Results: Patients had an average age of 60 years; and 16 of them were males. The disease was most commonly manifest ed by abdominal mass, weight loss, and anemia. Twenty one patients had a mass smaller than 10cm; and in 33 patients KIT test was positive. In the follow-up, 5 patients experienced relapse and 3 succumbed due to advanced cancer. Conclusion: Primary results showed that GISTs might have different manifestations and incidence in Iran compared to other parts of the world. We hope that this study could serve as a starting point for the better understanding and classification of this disease in Iran and for development of improved management strategies.

  4. Advances in our understanding of adipose tissue homeostasis

    Stern, Jennifer H.; Scherer, Philipp E.

    2014-01-01

    In 2014, numerous noteworthy papers focusing on adipose tissue physiology were published. Many of these articles showed the promise of adipose-tissue-targeted approaches for therapeutic intervention in obesity and type 2 diabetes mellitus. Here, we highlight advances in the development and maintenance of brown and/or beige adipocytes and the metabolic implications of infammation in adipose tissues.

  5. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

    Geyh, S; Oz, S; Cadeddu, R-P; Fröbel, J; Brückner, B; Kündgen, A; Fenk, R; Bruns, I; Zilkens, C; Hermsen, D; Gattermann, N; Kobbe, G; Germing, U; Lyko, F; Haas, R; Schroeder, T

    2013-09-01

    Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS. PMID:23797473

  6. Developmental programming, adiposity, and reproduction in ruminants.

    Symonds, M E; Dellschaft, N; Pope, M; Birtwistle, M; Alagal, R; Keisler, D; Budge, H

    2016-07-01

    Although sheep have been widely adopted as an animal model for examining the timing of nutritional interventions through pregnancy on the short- and long-term outcomes, only modest programming effects have been seen. This is due in part to the mismatch in numbers of twins and singletons between study groups as well as unequal numbers of males and females. Placental growth differs between singleton and twin pregnancies which can result in different body composition in the offspring. One tissue that is especially affected is adipose tissue which in the sheep fetus is primarily located around the kidneys and heart plus the sternal/neck region. Its main role is the rapid generation of heat due to activation of the brown adipose tissue-specific uncoupling protein 1 at birth. The fetal adipose tissue response to suboptimal maternal food intake at defined stages of development differs between the perirenal abdominal and pericardial depots, with the latter being more sensitive. Fetal adipose tissue growth may be mediated in part by changes in leptin status of the mother which are paralleled in the fetus. Then, over the first month of life plasma leptin is higher in females than males despite similar adiposity, when fat is the fastest growing tissue with the sternal/neck depot retaining uncoupling protein 1, whereas other depots do not. Future studies should take into account the respective effects of fetal number and sex to provide more detailed insights into the mechanisms by which adipose and related tissues can be programmed in utero. PMID:27173959

  7. Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation.

    Ryan, Michael J; Coleman, T Taylor; Sasser, Jennifer M; Pittman, Katarina M; Hankins, Michael W; Stec, David E

    2016-05-15

    Obesity is a risk factor for cardiovascular disease and is associated with increased plasma levels of the adipose-derived hormone leptin. Vascular smooth muscle cells (VSMC) express leptin receptors (LepR); however, their physiological role is unclear. We hypothesized that leptin, at levels to mimic morbid obesity, impairs vascular relaxation. To test this, we used control and VSM-LepR knockout mice (VSM-LepR KO) created with a tamoxifen-inducible specific Cre recombinase to delete the LepR gene in VSMC. Control (10-12 wk old) and VSM-LepR KO (10-12 wk old) mice were fed a diet containing tamoxifen (50 mg/kg) for 6 wk, after which vascular reactivity was studied in isolated carotid arteries using an organ chamber bath. Vessels were incubated with leptin (100 ng/ml) or vehicle (0.1 mM Tris·HCl) for 30 min. Leptin treatment resulted in significant impairment of vessel relaxation to the endothelial-specific agonist acetylcholine (ACh). When these experiments were repeated in the presence of the superoxide scavenger tempol, relaxation responses to ACh were restored. VSM-LepR deletion resulted in a significant attenuation of leptin-mediated impaired ACh-induced relaxation. These data show that leptin directly impairs vascular relaxation via a VSM-LepR-mediated mechanism, suggesting a potential pathogenic role for leptin to increase cardiovascular risk during obesity. PMID:26936780

  8. Stromal mesenchyme cell genes of the human prostate and bladder

    Pascal Laura E

    2005-12-01

    Full Text Available Abstract Background Stromal mesenchyme cells play an important role in epithelial differentiation and likely in cancer as well. Induction of epithelial differentiation is organ-specific, and the genes responsible could be identified through a comparative genomic analysis of the stromal cells from two different organs. These genes might be aberrantly expressed in cancer since cancer could be viewed as due to a defect in stromal signaling. We propose to identify the prostate stromal genes by analysis of differentially expressed genes between prostate and bladder stromal cells, and to examine their expression in prostate cancer. Methods Immunohistochemistry using antibodies to cluster designation (CD cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR. Results The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13+ cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13-. A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK, was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer. Conclusion Our findings show that the histologically similar stromas of the prostate and

  9. 3D microtumors in vitro supported by perfused vascular networks.

    Sobrino, Agua; Phan, Duc T T; Datta, Rupsa; Wang, Xiaolin; Hachey, Stephanie J; Romero-López, Mónica; Gratton, Enrico; Lee, Abraham P; George, Steven C; Hughes, Christopher C W

    2016-01-01

    There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This "organs-on-chips" approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This "tumor-on-a-chip" platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID:27549930

  10. 3D microtumors in vitro supported by perfused vascular networks

    Sobrino, Agua; Phan, Duc T. T.; Datta, Rupsa; Wang, Xiaolin; Hachey, Stephanie J.; Romero-López, Mónica; Gratton, Enrico; Lee, Abraham P.; George, Steven C.; Hughes, Christopher C. W.

    2016-01-01

    There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This “organs-on-chips” approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This “tumor-on-a-chip” platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID:27549930

  11. Transplanted bone marrow stromal cells improve cognitive dysfunction due to aging hypoperfusion in rats

    HUANG Jing; YIN Shao-jun; CHEN Yu-juan; BIAN Wei-hong; YU Jing; ZHAO Yu-wu; LIU Xue-yuan

    2010-01-01

    Background Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.Methods Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group,D-gal+2VO group, D-gal+2VO+saline water group, and D-gal+2VO+BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation;moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).Results Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal+2VO+BMSC group showed significant improvement than the D-gal+2VO group but was still obviously worse than the control group (both P <0.05).There was no significant difference in swimming speed for all 5 groups.Conclusions D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.

  12. Data set for renal sinus fat volume and visceral adipose tissue volume on computed tomography

    Yoko Murakami

    2016-06-01

    Full Text Available Renal sinus fat is partially characteristic of peri-vascular adipose tissue, however, RSF volume (RSFV is associated with visceral adipose tissue (VATV. Therefore, the ratio of RSFV to VATV (RSFV/VATV ratio can distinguish the importance of RSF as an extension of VAT versus its perivascular effects. We assessed the association of RSFV/VATV ratio with coronary artery calcification score (CACS in 189 patients with suspected coronary artery disease. RSFV of the right kidney and VATV were quantified by using image data of unenhanced abdominal CT. CACS were measured on unenhanced ECG-gated CT images. This article contains data on explanatory scheme of how to measure RSFV on unenhanced abdominal CT, CT indication and exclusion criteria of study population, sex-adjusted association between RSFV with risk factors of coronary vascular diseases and metabolic indices, multivariate linear regression analysis with CACS as the dependent variable in the total study population. The data are supplemental to our original research article describing detailed association between RSFV/VATV ratio and CACS including sub-groups analyses classified by the age of 70 “Renal sinus fat volume on computed tomography in middle-aged patients at risk for cardiovascular disease and its association with coronary artery calcification” Murakami et al. [1].

  13. Stromal cell contribution to human follicular lymphoma pathogenesis

    Frédéric eMourcin

    2012-09-01

    Full Text Available Follicular lymphoma (FL is the prototypical model of indolent B-cell lymphoma displaying a strong dependence on a specialized cell microenvironment mimicking normal germinal center. Within malignant cell niches in invaded lymph nodes and bone marrow, external stimuli provided by infiltrating stromal cells make a pivotal contribution to disease development, progression, and drug resistance. The crosstalk between FL B cells and stromal cells is bidirectional, causing activation of both partners. In agreement, FL stromal cells exhibit specific phenotypic, transcriptomic, and functional properties. This review highlights the critical pathways involved in the direct tumor-promoting activity of stromal cells but also their role in the organization of FL cell niche through the recruitment of accessory immune cells and their polarization to a B-cell supportive phenotype. Finally, deciphering the interplay between stromal cells and FL cells provides potential new therapeutic targets with the aim to mobilize malignant cells outside their protective microenvironment and increase their sensitivity to conventional treatment.

  14. Cellular and extracellular matrix modulation of corneal stromal opacity.

    Torricelli, Andre A M; Wilson, Steven E

    2014-12-01

    Stromal transparency is a critical factor contributing to normal function of the visual system. Corneal injury, surgery, disease and infection elicit complex wound healing responses that serve to protect against insults and maintain the integrity of the cornea, and subsequently to restore corneal structure and transparency. However, in some cases these processes result in prolonged loss of corneal transparency and resulting diminished vision. Corneal opacity is mediated by the complex actions of many cytokines, growth factors, and chemokines produced by the epithelial cells, stromal cells, bone marrow-derived cells, lacrimal tissues, and nerves. Myofibroblasts, and the disorganized extracellular matrix produced by these cells, are critical determinants of the level and persistence of stromal opacity after corneal injury. Decreases in corneal crystallins in myofibroblasts and corneal fibroblasts contribute to cellular opacity in the stroma. Regeneration of a fully functional epithelial basement membrane (BM) appears to have a critical role in the maintenance of corneal stromal transparency after mild injuries and recovery of transparency when opacity is generated after severe injuries. The epithelial BM likely has a regulatory function whereby it modulates epithelium-derived growth factors such as transforming growth factor (TGF) β and platelet-derived growth factor (PDGF) that drive the development and persistence of myofibroblasts from precursor cells. The purpose of this article is to review the factors involved in the maintenance of corneal transparency and to highlight the mechanisms involved in the appearance, persistency and regression of corneal opacity after stromal injury. PMID:25281830

  15. Giant liver hemangioma in patient with ileal gastrointestinal stromal tumor

    Antić Vasilije

    2014-01-01

    Full Text Available Introduction. Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the gastrointestinal tract. These tumors represent more than 80% of all mesenchymal tumors found in the gastrointestinal tract, though they account for only approximately 3% of all gastrointestinal malignancies. Literature offers case reports, which describe symptomatic gastrointestinal stromal tumors and they generally represent patients with larger tumors. Case report. We present the case of a small gastrointestinal stromal tumor in a 40-year-old man, with associated giant liver hemangioma and fever, and with history of abdominal discomfort and fever. Clinical examination revealed hepatosplenomegaly, palpable mass in the right lower abdomen, and signs of neurofibromatosis type 1 (Morbus von Recklinghausen. Computed tomography revealed a giant tumor in the right lobe of the liver. Magnetic resonance showed abscess in the hemangioma of the liver. An intestinal tumor was incidentally found and excised during surgical laparotomy. An intestinal gastrointestinal stromal tumor was revealed by histopathology and confirmed by immunohistochemistry. Although a multidisciplinary team proposed surgical removal of the liver tumor mass, the surgeons decided to follow up the patient because of a high risk of new intervention. Conclusion. According to the available data, this is a very rare case of small intestinal gastrointestinal stromal tumor, with symptoms of fever and giant abscess in the liver hemangioma.

  16. Leaky vessels as a potential source of stromal acidification in tumours

    Martin, Natasha K.

    2010-12-01

    Malignant tumours are characterised by higher rates of acid production and a lower extracellular pH than normal tissues. Previous mathematical modelling has indicated that the tumour-derived production of acid leads to a gradient of low pH in the interior of the tumour extending to a normal pH in the peritumoural tissue. This paper uses mathematical modelling to examine the potential of leaky vessels as an additional source of stromal acidification in tumours. We explore whether and to what extent increasing vascular permeability in vessels can lead to the breakdown of the acid gradient from the core of the tumour to the normal tissue, and a progressive acidification of the peritumoural stroma. We compare our mathematical simulations to experimental results found in vivo with a tumour implanted in the mammary fat pad of a mouse in a window chamber construct. We find that leaky vasculature can cause a net acidification of the normal tissue away from the tumour boundary, though not a progressive acidification over time as seen in the experiments. Only through progressively increasing the leakiness can the model qualitatively reproduce the experimental results. Furthermore, the extent of the acidification predicted by the mathematical model is less than as seen in the window chamber, indicating that although vessel leakiness might be acting as a source of acid, it is not the only factor contributing to this phenomenon. Nevertheless, tumour destruction of vasculature could result in enhanced stromal acidification and invasion, hence current therapies aimed at buffering tumour pH should also examine the possibility of preventing vessel disruption.

  17. Hybrid adipogenic implants from adipose stem cells for soft tissue reconstruction in vivo.

    Moioli, Eduardo K; Chen, Mo; Yang, Rujing; Shah, Bhranti; Wu, June; Mao, Jeremy J

    2010-11-01

    A critical barrier in tissue regeneration is scale-up. Bioengineered adipose tissue implants have been limited to ∼10  mm in diameter. Here, we devised a 40-mm hybrid implant with a cellular layer encapsulating an acellular core. Human adipose-derived stem cells (ASCs) were seeded in alginate. Poly(ethylene)glycol-diacrylate (PEGDA) was photopolymerized into 40-mm-diameter dome-shaped gel. Alginate-ASC suspension was painted onto PEGDA surface. Cultivation of hybrid constructs ex vivo in adipogenic medium for 28 days showed no delamination. Upon 4-week in vivo implantation in athymic rats, hybrid implants well integrated with host subcutaneous tissue and could only be surgically separated. Vascularized adipose tissue regenerated in the thin, painted alginate layer only if ASC-derived adipogenic cells were delivered. Contrastingly, abundant fibrous tissue filled ASC-free alginate layer encapsulating the acellular PEGDA core in control implants. Human-specific peroxisome proliferator-activated receptor-γ (PPAR-γ) was detected in human ASC-seeded implants. Interestingly, rat-specific PPAR-γ was absent in either human ASC-seeded or ASC-free implants. Glycerol content in ASC-delivered implants was significantly greater than that in ASC-free implants. Remarkably, rat-specific platelet/endothelial cell adhesion molecule (PECAM) was detected in both ASC-seeded and ASC-free implants, suggesting anastomosis of vasculature in bioengineered tissue with host blood vessels. Human nuclear staining revealed that a substantial number of adipocytes were of human origin, whereas endothelial cells of vascular wall were of chemaric human and nonhuman (rat host) origins. Together, hybrid implant appears to be a viable scale-up approach with volumetric retention attributable primarily to the acellular biomaterial core, and yet has a biologically viable cellular interface with the host. The present 40-mm soft tissue implant may serve as a biomaterial tissue expander for

  18. Plant vascular development

    Rybel, De Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate

  19. Adipose-derived stem cells - Methods and protocols

    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.......

  20. Mouse endometrial stromal cells produce basement-membrane components

    Wewer, U M; Damjanov, A; Weiss, J;

    1986-01-01

    During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The....... Mouse decidual cells isolated from 6- to 7-day pregnant uteri explanted in vitro continue to synthesize basement-membrane-like extracellular matrix. Using immunohistochemistry and metabolic labeling followed by immunoprecipitation, SDS-PAGE, and fluorography, it was shown that the decidual cells...... undergo pseudodecidualization. We thus showed that stromal cells from pregnant and nonpregnant mouse uteri synthesize significant amounts of basement-membrane components in vitro, and hence could serve as a good model for the study of normal basement-membrane components....