Application of adipose-derived stem cells in treating fibrosis.
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ABSTRACT:
SUBMITTER: Li ZJ
PROVIDER: S-EPMC8641015 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLymphedema is a chronic, debilitating and incurable disease that affects 0.13%-2% of the global population. Emerging evidence indicates that adipose-derived stem cells (ADSCs) might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy.AimTo summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials.MethodsA systematic search was performed on four databases - PubMed, Clinicaltrials.gov, the evidence-based Cochrane Library, and OVID - using the following search string: ("lymphedema" or "lymphoedema" or "lymphangiogenesis") and ("adipose-derived stem cells" or "adipose-derived stromal cells" or "adipose-derived regenerative cells"). A manual search was performed by skimming the references of relevant studies. Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included.ResultsA total of eight research articles published before November 2019 were included for this analysis. Five articles focused on animal studies and another three focused on clinical trials. ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies. The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy. Three sequential clinical trials were conducted on breast cancer-related lymphedema patients, and all showed favorable results.ConclusionADSC-based therapy is a promising option for treating lymphedema. Large-scale, multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.
| S-EPMC7415250 | biostudies-literature
Project description:Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides cytokines, proteins, and growth factors, the therapeutic effect of secretome is hidden in non-coding RNAs such as miR-21, miR-24, and miR-26 carried via exosomes secreted by adequate cells. The whole secretome, including ASC-derived exosomes (ASC-exos) has been proven in many studies to have immunomodulatory, proangiogenic, neurotrophic, and epithelization activity and can potentially be used for neurodegenerative, cardiovascular, respiratory, inflammatory, and autoimmune diseases as well as wound healing treatment. Due to limitations in the use of stem cells in cell-based therapy, its secretome with emphasis on exosomes seems to be a reasonable and safer alternative with increased effectiveness and fewer side effects. Moreover, the great advantage of cell-free therapy is the possibility of biobanking the ASCs secretome. In this review, we focus on the current state of knowledge on the use of the ASCs secretome in stem cell-free therapy.
| S-EPMC8231996 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21-secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)-induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis-related factors such as ?-smooth muscle actin (?-SMA), collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with the Empty_ADSCs by inhibition of p-JNK, NF-?B and p-Smad2/3 signalling. ?-lactoalbumin (LA) and lactotransferrin (LTF), secretory factors produced from FGF21_ADSCs inhibited TGF-?1-induced expression of ?-SMA and collagen in LX-2 cells. These results suggest that transplantation of FGF21_ADSCs inhibited liver fibrosis more effectively than Empty_ADSCs, possibly via secretion of ?-LA and LTF.
| S-EPMC6156392 | biostudies-literature
Project description:Adipose-derived stem cells (ASCs) represent a promising tool for soft tissue engineering as well as for clinical treatment of inflammatory and autoimmune pathologies. The well-characterized multi-differentiation potential and self-renewal properties of ASCs are coupled with their immunomodulatory ability in providing therapeutic efficacy. Yet, their impact in immune or inflammatory disorders might rely both on cell contact-dependent mechanisms and paracrine effects, resulting in the release of various soluble factors that regulate immune cells functions. Despite the widespread use of ASCs in clinical trials addressing several pathologies, the pathophysiological mechanisms at the basis of their clinical use have been not yet fully investigated. In particular, a thorough analysis of ASC immunomodulatory potential is mandatory. Here we explore such molecular mechanisms involved in ASC immunomodulatory properties, emphasizing the relevance of the milieu composition. We review the potential clinical use of ASC secretome as a mediator for immunomodulation, with a focus on in vitro and in vivo environmental conditions affecting clinical outcome. We describe some potential strategies for optimization of ASCs immunomodulatory capacity in clinical settings, which act either on adult stem cells gene expression and local microenvironment. Finally, we discuss the limitations of both allogeneic and autologous ASC use, highlighting the issues to be fixed in order to significantly improve the efficacy of ASC-based cell therapy.
| S-EPMC7180192 | biostudies-literature
Project description:Peritoneal fibrosis (PF) represents a long-term complication of peritoneal dialysis (PD), affecting the peritoneal membrane (PM) function. Adipose tissue-derived mesenchymal stem cells (ASC) display immunomodulatory effects and may represent a strategy to block PF. The aim of this study was to analyze the effect of ASC in an experimental PF model developed in uremic rats. To mimic the clinical situation of patients on long-term PD, a combo model, characterized by the combination of PF and chronic kidney disease (CKD), was developed in Wistar rats. Rats were fed with a 0.75% adenine-containing diet, for 30 days, to induce CKD with uremia. PF was induced with intraperitoneal injections of chlorhexidine gluconate (CG) from day 15 to 30. 1 × 106 ASC were intravenously injected at days 15 and 21. Rats were divided into 5 groups: control, normal rats; CKD, rats receiving adenine diet; PF, rats receiving CG; CKD+PF, CKD rats with PF; CKD+PF+ASC, uremic rats with PF treated with ASC. PF was assessed by Masson trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry, multiplex analysis, and qPCR. When compared with the control and CKD groups, GC administration induced a striking increase in PM thickness and inflammation in the PF and CKD+PF groups. The development of PF was blocked by ASC treatment. Further, the upregulation of profibrotic factors (TGF-?, fibronectin, and collagen) and the increased myofibroblast expression observed in the CKD+PF group were significantly ameliorated by ASC. Beyond the antifibrotic effect, ASC showed an anti-inflammatory effect avoiding leucocyte infiltration and the overexpression of inflammatory cytokines (IL-1?, TNF-?, and IL-6) in the PM induced by GC. ASC were effective in preventing the development of PF in the experimental model of CKD+PF, probably due to their immunomodulatory properties. These results suggest that ASC may represent a potential strategy for treating long-term PD-associated fibrosis.
| S-EPMC7256710 | biostudies-literature
Project description:BackgroundThe therapeutic effect of mesenchymal stem cells (MSCs) from human adipose tissue on renal interstitial fibrosis has been demonstrated by several groups. However, the way to enhance the renoprotective effect of adipose-derived mesenchymal stem cells (AMSCs) and the possible mechanisms are still unclear. The present study aimed to determine whether glial cell line-derived neurotrophic factor (GDNF)-modified AMSCs hold an enhanced protective effect on renal fibrosis.MethodsAMSCs were isolated and purified for culture. The gene GDNF has been constructed to transfect into AMSCs. The ability of GFP-AMSCs and GDNF-AMSCs supernatants to promote tube formation of endothelial cells, repair damaged endothelial cell junctions, and improve endothelial cell function was compared by using tube formation assay, immunofluorescence techniques, and vascular ring assay, respectively. Furthermore, HE and Masson staining were used to observe the histological morphology of the kidney in vivo. Peritubular capillary changes were detected and analyzed by fluorescence microangiography (FMA). Meanwhile, the hypoxia, oxidative stress, fibrotic markers, and PI3K/Akt pathway proteins were measured by western blot or qRT-PCR technics.ResultsCompared with GFP-AMSCs only, GDNF-AMSCs could enhance the repair of injured endothelial cells and promote angiogenesis through secreting more growth factors in the supernatant of GDNF-AMSC culture media demonstrated in vitro studies. Studies in vivo, unilateral ureteral obstruction (UUO)-induced mice were injected with transfected AMSCs through their tail veins. We showed that enhanced homing of AMSCs was observed in the GDNF-AMSC group compared with the GFP-AMSC group. The animals treated with GDNF-AMSCs exhibited an improvement of capillary rarefaction and fibrosis induced by obstructed kidney compared with the GFP-AMSC group. Furthermore, we reported that GDNF-AMSCs protect renal tissues against microvascular injuries via activation of the PI3K/Akt signaling pathway. Therefore, GDNF-AMSCs further ameliorated the tissue hypoxia, suppressed oxidative stress, and finally inhibited endothelial to mesenchymal transition noting by decreased coexpression of endothelial cell (CD31) and myofibroblast (a-SMA) markers.ConclusionCollectively, our data indicated that the GDNF gene enhances the ability of AMSCs in improving renal microcirculation through PI3K/Akt/eNOS signaling pathway and afterward inhibit the EndMT process and kidney fibrogenesis, which should have a vast of implications in designing future remedies for chronic kidney disease (CKD) treatment.
| S-EPMC7792009 | biostudies-literature
Project description:Background and aimsADSCs transplantation had been shown in some experimental models of kidney damage that it improves kidney function and reduces fibrosis. In this study we evaluated the effect of human adipose tissue-derived stem cell (hADSC) therapy in a chronic kidney damage experimental model.MethodsA chronic kidney injury was induced by daily orogastric administration of adenine (100mg/kg) to male Wistar rats for 28 days. hADSCs were isolated, expanded and characterized before transplantation. hADSC administration was performed in a tail vein at a dose of 2 x106 cells/animal. Animals were sacrificed at 7 days post-treatment. The percentage of fibrotic tissue, serum and urine levels of urea, creatinine, total protein and renal mRNA of COL1A1, TGFB1, CTGF, ACTA2, IL6, IL10, TNF were analyzed.ResultshADSCs treatment significantly reduces kidney fibrosis, improves urea and creatinine serum and urine levels, and diminishes COL1A1, TGFB1, CTGF, ACTA2 mRNA kidney levels.ConclusionsThese results showed that cell therapy using hADSCs improves renal function and reduces fibrosis.
| S-EPMC5744925 | biostudies-literature
Project description:Scleroderma is a group of skin-fibrosing diseases for which there are no effective treatments. A feature of the skin fibrosis typical of scleroderma is atrophy of the dermal white adipose tissue (DWAT). Adipose tissue contains adipose-derived mesenchymal stromal cells (ADSCs) that have regenerative and reparative functions; however, whether DWAT atrophy in fibrosis is accompanied by ADSC loss is poorly understood, as are the mechanisms that might maintain ADSC survival in fibrotic skin. Here, we have shown that DWAT ADSC numbers were reduced, likely because of cell death, in 2 murine models of scleroderma skin fibrosis. The remaining ADSCs showed a partial dependence on dendritic cells (DCs) for survival. Lymphotoxin ? (LT?) expression in DCs maintained ADSC survival in fibrotic skin by activating an LT? receptor/?1 integrin (LT?R/?1 integrin) pathway on ADSCs. Stimulation of LT?R augmented the engraftment of therapeutically injected ADSCs, which was associated with reductions in skin fibrosis and improved skin function. These findings provide insight into the effects of skin fibrosis on DWAT ADSCs, identify a DC-ADSC survival axis in fibrotic skin, and suggest an approach for improving mesenchymal stromal cell therapy in scleroderma and other diseases.
| S-EPMC5096920 | biostudies-literature
Project description:In plastic surgery, the maneuverability and safety of autologous fat transplantation have become increasingly recognized and continuously improved. However, the uncertainty of adipocyte survival makes it difficult to predict postoperative effects. Adipose?derived stem cells (ADSCs) exhibit remarkable paracrine activity, and the number of ADSCs in adipose tissue is closely related to tissue survival. Maternally expressed gene 3 (MEG3) is known to modulate the apoptosis of various cell types. The present study aimed to evaluate the hypothesis that MEG3 serves an important role in ADSC apoptosis by regulating the expression of p53, and to explore the regulatory mechanisms of p53 in ADSC apoptosis. MEG3 was overexpressed in ADSCs and these cells were evaluated for viability, TP53 expression, apoptosis, morphology, and Bax and Bcl?2 expression by performing MTT assays, reverse transcription?quantitative PCR, flow cytometry analysis and western blotting. This study demonstrated that MEG3 may have an important role in the spontaneous apoptosis of ADSCs, and apoptosis induced by oxidative stress. In addition, this study revealed that p53 had a regulatory role in the downstream Bcl?2/Bax pathway. This study provides insight into the role of MEG3 in ADSC apoptosis, thereby facilitating the survival of ADSCs during adipose tissue transplantation. Further in vivo and in vitro experiments should be conducted, along with the development of clinical applications.
| S-EPMC7185308 | biostudies-literature
Project description:Cell therapies present a feasible option for the treatment of degenerated cartilaginous and intervertebral disc (IVD) tissues. Microenvironments of these tissues are specific and often differ from the microenvironment of cells that, could be potentially used for therapy, e.g. human adipose-derived stem cells (hASC). To ensure safe and efficient implantation of hASC, it is important to evaluate how microenvironmental conditions at the site of implantation affect the implanted cells. This study has demonstrated that cartilaginous tissue-specific osmolarities ranging from 400-600 mOsm/L affected hASC in a dose- and time-dependent fashion in comparison to 300 mOsm/L. Increased osmolarities resulted in transient (nuclear DNA and actin reorganisation) and non-transient, long-term morphological changes (vesicle formation, increase in cell area, and culture morphology), as well as reduced proliferation in monolayer cultures. Increased osmolarities diminished acid proteoglycan production and compactness of chondrogenically induced pellet cultures, indicating decreased chondrogenic potential. Viability of hASC was strongly dependent on the type of culture, with hASC in monolayer culture being more tolerant to increased osmolarity compared to hASC in suspension, alginate-agarose hydrogel, and pellet cultures, thus emphasizing the importance of choosing relevant in vitro conditions according to the specifics of clinical application.
| S-EPMC5051864 | biostudies-literature