Tissue with high intelligence quotient Adipose-derived stem cells in neural regeneration

The aim of the present review is to highlight the possible neuroregenerative potential ol adipose-derived stem cells. The key property of stem cells is plasticity including self-renewal, multilineage differentiation, and migration, whereas the required property is transplantability. For a long time, embryonic stem cells were thought to be the only source of pluripotency, a dogma that has been challenged during the last decade. Today, an alternative option might be adipose-derived stem cells, as easily accessible, ethical and autologous cellular source. Recent knowledge of adipobiology increasingly recognizes that adipose tissue is the major endo- and paracrine organ of the human body. Likewise, numerous neuropetides, neurotrophic factors, neurotransmitters, hypothalamic and steroid hormones and their receptors are shared by adipose tissue and brain. Accordingly, the regenerative potential of neuroprotective factor-secreting adipose-derived stem cells is outlined. Whether the possible benefits of adipose stem cell-based therapy may be mediated via cell transdifferentiation and/or paracrine mechanisms remains to further be evaluated.

0Adipose-derived stem cells: Implications in tissue regeneration

Adipose-derived stem cells(ASCs) are mesenchymal stem cells(MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differ-entiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs dam-aged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.

Translational products of adipose tissue-derived mesenchymal stem cells:Bench to bedside applications

With developments in the field of tissue engineering and regenerative medicine,the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians.Among all the available biological tissues,research and exploration of adipose tissue have become more robust.Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential.The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth,proliferation,and differentiation.Adipose tissue,apart from being the powerhouse of energy storage,also functions as the largest endocrine organ,with the release of various adipokines.The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues.The results of adipose-derived stemcell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis,fat graft integration,and survival within the recipient tissue and promote the regeneration of tissue are promising.Adipose tissue gives rise to various by-products upon processing.This article highlights the significance and the usage of various adipose tissue by-products,their individual characteristics,and their clinical applications.

Clinical and Magnetic Resonance Image Changes of Platelet-Rich Plasma Therapy in Combination with Human Mesenchymal Stem Cells from Autologous Adipose Tissue for Knee Osteoarthritis Treatment

Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoarthritis treatment. Patients and Method: 30 patients including 26 females and 4 males;correspondingly, 60 knee joints were diagnosed with osteoarthritis with stages II - III of Kellgren and Lawrence, their mean age was 58.63 ± 11.11. All were injected with autologous platelet-rich plasma that was extracted by PRP set, APC 30 PRP PRCEDURE PRAK and autologously extracted mesenchymal stem cells from abdominal adipose tissue using the ADI-25-01 ADIPOSEPRCEDURE PRAK of USA. Results: After 12 months: the pain level according to VAS score at the right knee joint was decreased from 6.0 ± 1.28 before treatment to 1.9 ± 0.3;VAS score at the left knee joint was decreased from 6.43 ± 1.19 to 2.25 ± 0.43. Total Lequene score at right knee joint was decreased from 16.04 ± 1.57 before treatment to 4.31 ± 1.04, at left knee joint was decreased from 17.52 ± 1.74 before treatment to 5.15 ± 1.48. Total WOMAC score at right knee joint was decreased from 55.93 ± 5.56 to 10.37 ± 1.56;at left knee joint was decreased from 53.97 ± 5.57 to 10.07 ± 1.59. There were 86.77% joints with cartilage thickness change and the patellar cartilage thickness was increased from 1.56 ± 0.09 mm before treatment to 1.65 ± 0.09 mm. Conclusion: The treatment of knee osteoarthritis by platelet-rich plasma therapyin combination with mesenchymal stem cells from autologous adipose tissue is effective in reducing pain, improving patient's mobility and walking function, reforming articular cartilage thickness on magnetic resonance image.

Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease

Adipose tissue-deried stem cells( ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells(VECs), vascular smooth muscle cells(VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissueresident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction(AMI), ischemic cardiomyopathy(ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application.

Role of adipose tissue grafting and adipose-derived stem cells in peripheral nerve surgery

The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.

Anti-osteoarthritis effect of a combination treatment with human adipose tissue-derived mesenchymal stem cells and thrombospondin 2 in rabbits

BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,mesenchymal stem cells(MSCs)have the potential for articular cartilage regeneration.Meanwhile,thrombospondin 2(TSP2)promotes the chondrogenic differentiation of MSCs.AIM To investigate whether TSP2 induces chondrogenic differentiation of human adipose-derived MSCs(hADMSCs)and potentiates the therapeutic effects of hADMSCs in OA rabbits.METHODS We investigated the chondrogenic potential of TSP2 in hADMSCs by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 small interfering RNA(siRNA)-treated stem cells.Anterior cruciate ligament transection surgery was performed in male New Zealand white rabbits,and 8 wk later,hADMSCs(1.7×10^6 or 1.7×10^7 cells)were injected into the injured knees alone or in combination with intra-articular injection of TSP2(100 ng/knee)at 2-d intervals.OA progression was monitored by gross,radiological,and histological examinations.RESULTS In hADMSC culture,treatment with TSP2 increased the expression of chondrogenic markers(SOX9 and collagen Ⅱ)as well as NOTCH signaling genes(JAGGED1 and NOTCH3),which were inhibited by TSP2 siRNA treatment.In vivo,OA rabbits treated with hADMSCs or TSP2 alone exhibited lower degree of cartilage degeneration,osteophyte formation,and extracellular matrix loss 8 wk after cell transplantation.Notably,such cartilage damage was further alleviated by the combination of hADMSCs and TSP2.In addition,synovial inflammatory cytokines,especially tumor-necrosis factor-α,markedly decreased following the combination treatment.CONCLUSION The results indicate that TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling,and that combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.

Ameliorative effects of human adipose tissue-derived mesenchymal stem cells on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats

Mesenchymal stem cells have been previously shown to exert an immunomodulatory function. The present study sought to investigate the effects of multipotential human adipose tissue-derived mesenchymal stem cells （hAdMSCs） on disease progression and cytokine expression in Lewis rats with experimental autoimmune encephalomyelitis （EAE） induced by myelin basic protein. The duration of EAE paralysis in the group treated on day 7 posfimmunization with 5 × 10^6 hAdMSCs was significantly reduced compared with the vehicle-treated controls and the 1 x 106 hAdMSC- treated group. The duration of EAE paralysis in the groups treated with 5 × 10^6 hAdMSCs on both day 1 and day 7 postimmunization was significantly reduced compared with the vehicle-treated controls and the groups treated with 5 × 10^6 hAdMSCs on both day 7 and day 10 postimmunization. The mRNA expression of interleukin-10 and indoleamine 2, 3-dioxygenase was significantly decreased in the hAdMSC-treated group compared with the vehicle-treated group. These findings suggest that the ameliorative effects of hAdMSCs on EAE symptoms operate in a dose- and time-dependent manner and can be mediated in part by the ample production of anti-inflammatory cytokines.

Immunomodulatory effects of mesenchymal stem cells derived from adipose tissues in a rat orthotopic liver transplantation model

BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSCs clearly inhibit recipient-derived T lymphocyte proliferation in MLC and significantly alleviate acute rejection following orthotopic liver transplantation in rats.

Osteogenesis of Adipose-Derived Stem Cells

Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.

Adipose-derived mesenchymal stromal/stem cells: An update on their phenotype in vivo and in vitro

Adipose tissue is a rich, ubiquitous and easily acces-sible source for multipotent stromal/stem cells and has, therefore, several advantages compared to other sourc-es of mesenchymal stromal/stem cells. Several studies have tried to identify the origin of the stromal/stem cell population within adipose tissue in situ. This is a complicated attempt because no marker has currently been described which unambiguously identifies native adipose-derived stromal/stem cells(ASCs). Isolated and cultured ASCs are a non-uniform preparation consisting of several subsets of stem and precursor cells. Cultured ASCs are characterized by their expression of a panel of markers(and the absence of others), whereas their in vitro phenotype is dynamic. Some markers were ex-pressed de novo during culture, the expression of some markers is lost. For a long time, CD34 expression was solely used to characterize haematopoietic stem and progenitor cells, but now it has become evident that it is also a potential marker to identify an ASC subpopula-tion in situ and after a short culture time. Nevertheless, long-term cultured ASCs do not express CD34, perhaps due to the artificial environment. This review gives an update of the recently published data on the origin and phenotype of ASCs both in vivo and in vitro. In addition, the composition of ASCs(or their subpopula-tions) seems to vary between different laboratories andpreparations. This heterogeneity of ASC preparationsmay result from different reasons. One of the main problems in comparing results from different laborato-ries is the lack of a standardized isolation and culture protocol for ASCs. Since many aspects of ASCs, suchas the differential potential or the current use in clinical trials, are fully described in other recent reviews, this review further updates the more basic research issues concerning ASCs' subpopulations, heterogeneity andculture standardization.

Neuronal differentiation of adipose-derived stem cells and their transplantation for cerebral ischemia

OBJECTIVE： To review published data on the biological characteristics, differentiation and applications of adipose-derived stem cells in ischemic diseases. DATA RETRIEVAL： A computer-based online search of reports published from January 2005 to June 2012 related to the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia was performed in Web of Science using the key words ＂adipose-derived stem cells＂, ＂neural-like cells＂, ＂transplantation＂, ＂stroke＂, and ＂cerebral ischemia＂. SELECTION CRITERIA： The documents associated with the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia were selected, and those published in the last 3-5 years or in authoritative journals were preferred in the same field. Totally 89 articles were obtained in the initial retrieval, of which 53 were chosen based on the inclusion criteria. MAIN OUTCOME MEASURES： Biological characteristics and induced differentiation of adipose-derived stem cells and cell transplantation for disease treatment as well as the underlying mechanism of clinical application. RESULTS： The advantages of adipose-derived stem cells include their ease of procurement, wide availability, rapid expansion, low tumorigenesis, low immunogenicity, and absence of ethical constraints. Preclinical experiments have demonstrated that transplanted adipose-derived stem cells can improve neurological functions, reduce small regions of cerebral infarction, promote angiogenesis, and express neuron-specific markers. The improvement of neurological functions was demonstrated in experiments using different methods and time courses of adipose-derived stem cell transplantation, but the mechanisms remain unclear. CONCLUSION： Further research into the treatment of ischemic disease by adipose-derived stem cell transplantation is needed to determine their mechanism of action.

Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells

AIM: To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC.METHODS: BMSCs were obtained from patients under-going total hip arthroplasty and ADSC from human adi-pose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver develop-ment using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differ-entiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed. RESULTS: BMSC and ADSC exhibited a fibroblastic mor-phology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thy1 de-creased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to in-creased liver-enriched transcription factors (C/EBPβ and HNF4α), as demonstrated by adenoviral expression vec-tors.CONCLUSION: Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation ca-pacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.

Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration

Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation,which are continuously regulated by signals from the extracellular matrix(ECM)microenvironment.Therefore,the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior.Although the acellular ECM of specific tissues and organs(such as the skin,heart,cartilage,and lung)can mimic the natural microenvironment required for stem cell differentiation,the lack of donor sources restricts their development.With the rapid development of adipose tissue engineering,decellularized adipose matrix(DAM)has attracted much attention due to its wide range of sources and good regeneration capacity.Protocols for DAM preparation involve various physical,chemical,and biological methods.Different combinations of these methods may have different impacts on the structure and composition of DAM,which in turn interfere with the growth and differentiation of stem cells.This is a narrative review about DAM.We summarize the methods for decellularizing and sterilizing adipose tissue,and the impact of these methods on the biological and physical properties of DAM.In addition,we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration(such as adipose tissue),repair(such as wounds,cartilage,bone,and nerves),in vitro bionic systems,clinical trials,and other disease research.

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cellsAdipose mesenchymal stem cells in the field of bone tissue engineering

Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians.Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility,biodegradability and osteoinductivity.Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells(MSCs).In particular,a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue.These adipose stem cells(ASCs)can be obtained in large quantities with little donor site morbidity or patient discomfort,in contrast to the invasive and painful isolation of bone marrow MSCs.The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models,with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients.Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration,the lack of standardization in applied techniques makes the comparison between studies difficult.Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns,which must be resolved to permit application in regenerative medicine.

Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks

Scaffold-free techniques in the developmental tissue engineering area are designed to mimic in vivo embryonic processes with the aim of biofabricating,in vitro,tissues with more authentic properties.Cell clusters called spheroids are the basis for scaffold-free tissue engineering.In this review,we explore the use of spheroids from adult mesenchymal stem/stromal cells as a model in the developmental engineering area in order to mimic the developmental stages of cartilage and bone tissues.Spheroids from adult mesenchymal stromal/stem cells lineages recapitulate crucial events in bone and cartilage formation during embryogenesis,and are capable of spontaneously fusing to other spheroids,making them ideal building blocks for bone and cartilage tissue engineering.Here,we discuss data from ours and other labs on the use of adipose stromal/stem cell spheroids in chondrogenesis and osteogenesis in vitro.Overall,recent studies support the notion that spheroids are ideal"building blocks"for tissue engineering by“bottom-up”approaches,which are based on tissue assembly by advanced techniques such as three-dimensional bioprinting.Further studies on the cellular and molecular mechanisms that orchestrate spheroid fusion are now crucial to support continued development of bottom-up tissue engineering approaches such as three-dimensional bioprinting.

Autologous Adipose-Derived Mesenchymal Stem Cells Embedded in Platelet-Rich Fibrin in Diabetic Foot Ulcers

Context and Aim: Mesenchymal stem cells (MSCs) and platelet-rich fibrin (PRF) have emerged as ideal candidates for advanced therapies of various therapeutically-challenging diseases;however, their regenerative potential in diabetic foot ulcers (DFU) has not been well determined. In this study, we reviewed our clinical experience in mitigating chronic ulcer complications of diabetic foot through a conventional treatment of autologous adipose-derived MSCs embedded in PRF with pure PRF injections. Materials and Methods: The present study was carried out in 10 patients with an open DFU wound selected over a period of 1 year starting from April 2019. Patients were either injected with PRF alone (Group A) or injected with MSCs derived from adipose tissue (ADMSC) embedded in (PRF (Group B). Results: Patients in Group B had a better healing index when compared to Group A. Conclusion: Use of ADMSC embedded in PRF showed promising results to treat DFU.

Adipose-derived stromal/stem cells from different adipose depots in obesity development

The increasing prevalence of obesity is alarming because it is a risk factor for cardiovascular and metabolic diseases(such as type 2 diabetes). The occurrence of these comorbidities in obese patients can arise from white adipose tissue(WAT) dysfunctions, which affect metabolism, insulin sensitivity and promote local and systemic inflammation. In mammals, WAT depots at different anatomical locations(subcutaneous, preperitoneal and visceral) are highly heterogeneous in their morpho-phenotypic profiles and contribute differently to homeostasis and obesity development, depending on their ability to trigger and modulate WAT inflammation. This heterogeneity is likely due to the differential behavior of cells from each depot. Numerous studies suggest that adiposederived stem/stromal cells(ASC; referred to as adipose progenitor cells, in vivo)with depot-specific gene expression profiles and adipogenic and immunomodulatory potentials are keys for the establishment of the morphofunctional heterogeneity between WAT depots, as well as for the development of depot-specific responses to metabolic challenges. In this review, we discuss depot-specific ASC properties and how they can contribute to the pathophysiology of obesity and metabolic disorders, to provide guidance for researchers and clinicians in the development of ASC-based therapeutic approaches.