Effects Of Adipose-derived Stem Cells Research Articles

Adipocytes secretome from normal and tumor breast favor breast cancer invasion by metabolic reprogramming.

Adipose tissue is a major component of breast stroma. This study focused on delineating the effects of adipose stem cells (ASCs) derived from breast of healthy women and cancer patients with normal or tumor breast cells. The ASCs were induced to differentiate into adipocytes, and the subsequent adipocyte conditioned media (ACM) were evaluated for their fatty acid profile, adipokine secretion and influence on proliferation, migration and invasion on tumoral (MCF-7 and SUM159) and normal (HMEC) human breast cell lines. An enrichment of arachidonic acid was observed in ACM from tumor tissues. Adipose tissues from tumor free secrete twice as much leptin than those from proximal or distal to the tumor. All ACMs display proliferative activity and favor invasiveness of SUM159 cells compared to MCF-7 and HMEC. All ACMs induced lipid droplets accumulation in MCF-7 cells and increased CD36 expression in tumor cells. We conclude that among secreted factors analyzed, only arachidonic acid and leptin levels did discriminate ASCs from tumor-bearing and tumor-free breasts emphasizing the importance that other cell types could contribute to the adipose tissue secretome in a tumor context.

Retrospective Study on the Effect of Adipose-Derived Stem Cells on the Proliferation and Apoptosis of Keloid Fibroblasts Through the Suppression of ITGA2.

Keloid is characterized by excessive collagen accumulation and fibroblast growth, which are fibroproliferative disorders of injured skin, causing functional limitations. Studies have shown that adipose-derived stem cells (ADSCs) inhibit the bioactivity and fibrosis of keloid fibroblasts. However, the molecular mechanism of this effect of ADSCs on keloid formation has not been fully elucidated. This in vitro study used fibroblasts obtained from keloids. A consensus gene co-expression network was constructed to focus on identifying consensus gene co-expression modules associated with keloid fibroblasts. Differentially expressed genes (DEGs) were identified between keloid fibroblasts and normal dermal fibroblasts. A functional enrichment analysis was also performed with the DAVID database. A weighted gene co-expression network analysis (WGCNA) was used to screen keloid-related modules using the "WGCNA" R package, followed by hub gene selection in modules from the Protein-protein interaction network through the STRING database. Keloid fibroblasts and ADSCs were extracted and cultured. Proliferation and apoptosis were examined using a 5-ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. We identified 302 DEGs overlapping with a consensus analysis of clusters and a differential expression analysis between keloid fibroblasts and normal dermal fibroblasts. Most of these were involved in collagen binding, extracellular matrix organization, and the PI3K-Akt signaling pathway. WGCNA analysis selected a keloid-associated brown module. ITGA2 was identified as a novel marker in hub genes from the PPI network based on the degree and function of collagen modulation. Furthermore, the proliferation ability of keloid fibroblasts cultured in ADSC medium was inhibited while apoptosis was dramatically increased. Overexpression of ITGA2 reversed the decrease in ADSC-induced apoptosis and increased ADSC-reduced proliferation. Our study demonstrated that activation of ITGA2 plays a crucial role in ADSC-induced keloid fibroblast apoptosis and anti-proliferation effects. These results also improved our understanding of the molecular mechanism of the pathogenesis of keloid in response to ADSCs and may contribute to the further development of keloid therapy.

Adipose-Derived Stem Cells Attenuate Skin Fibrosis and Improve Fat Retention of a Localized Scleroderma Mouse Model.

Although autologous fat grafting is a feasible surgical technique to improve facial deformity in patients with localized scleroderma, its success is limited by the low graft retention induced by the local inflammatory environment. This study investigated the potential effect of adipose-derived stem cells (ASCs) on skin fibrosis and fat retention in a localized scleroderma mouse model. BALB/C nude mice that were induced by bleomycin to establish a localized scleroderma model were divided randomly into five groups: blank control; fat grafting; and low, moderate, and high doses of ASC-assisted fat grafting. The backs of the mice were subcutaneously injected with phosphate-buffered saline or fat, or fat with low, moderate, and high doses of ASCs (1 × 10 5 /mL, 5 × 10 5 /mL, and 25 × 10 5 /mL, respectively). The skin fibrosis and fat retention were analyzed after 1 month or 3 months, respectively. Compared to the disease model group, the fat-grafting group, and the low- and moderate-dose ASC-enriched groups, the high-dose ASCs significantly attenuated skin fibrosis, inhibited the production of type III collagen and transforming growth factor-β1, increased fat graft retention, enhanced the expression of angiogenesis-related cytokines and angiogenesis, and increased the expression of adipogenesis-related cytokines. The results demonstrated that high-dose ASCs attenuated skin fibrosis and improved fat retention in a localized scleroderma model by reducing inflammation and by promoting angiogenesis and adipogenesis. The authors further demonstrated that ASCs enhanced adipogenesis through the AKT/ERK signaling pathway. Fat grafting has been used to treat localized scleroderma patients but with low fat retention. In this study, ASC attenuated skin fibrosis and improved fat retention in the localized scleroderma model, providing evidence for cell therapy in future application of localized scleroderma treatment.

The Immunomodulatory Effect of Adipose-Derived Stem Cells in Xenograft Transplantation Model

Adipose-derived stem cells (ASCs) have demonstrated immunomodulatory and anti-inflammatory effects in preclinical studies. The purpose of this study was to evaluate the effects of ASCs on the survival of xenogeneic full-thickness skin grafts and compare intravenous and subcutaneous injections of ASCs. We divided 30 male C57BL/6 mice into control, intravenous (IV), and subcutaneous (SC) injection groups. In one group of 10 mice, mouse ASCs were intravenously injected after human full-thickness skin grafting (IV group). In another group of 10 mice, ASCs were directly injected into the subcutaneous plane under the xenogeneic grafts (SC group). An additional group of 10 mice received no treatment and served as controls. Bioluminescent imaging showed that ASCs were concentrated at the grafts during the study period in both IV and SC groups. We performed graft survival assessment, histologic examination, and immunohistochemistry analysis. ASCs significantly prolonged xenograft survival at postoperative week 2 in the SC group compared with the control group (P < .05). Histologic evaluation revealed fewer inflammatory reactions in the SC group than in the control group at 1 week posttransplantation. In addition, we observed relative reduction in CD4- and CD8-positive cells in the SC group compared with the control group. Intravenous injection of ASCs led to increased graft survival and decreased inflammatory reactions, but these differences were not statistically significant. The results of this study indicate that subcutaneous injection of ASCs promoted the survival of xenogeneic full-thickness skin grafts in mice. The underlying mechanisms of the immunosuppressive effects of ASCs should be further investigated.

Melatonin enhances autologous adipose-derived stem cells to improve mouse ovarian function in relation to the SIRT6/NF-κB pathway

BackgroundPremature ovarian insufficiency (POI) is the main cause of female infertility. Adipose-derived stem cells (ADSCs) are ideal candidates for the treatment of POI. However, some deficient biological characteristics of ADSCs limit their utility. This study investigated whether melatonin (MLT)-pretreated autologous ADSCs were superior to ADSCs alone in the treatment of the POI mouse model.MethodsAutologous ADSCs were isolated and cultured in MLT-containing medium. Surface markers of ADSCs were detected by flow cytometry. To determine the effect of MLT on ADSCs, CCK-8 assay was used to detect ADSCs proliferation and enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokines. The POI model was established by intraperitoneal injection of cyclophosphamide and busulfan. Then, MLT-pretreated autologous ADSCs were transplanted into mice by intraovarian injection. After 7 days of treatment, ovarian morphology, follicle counts, and sex hormones levels were evaluated by hematoxylin and eosin (H&E) staining and ELISA, and the recovery of fertility was also observed. The expressions of SIRT6 and NF-κB were detected by immunohistochemical (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsFlow cytometry showed that autologous ADSCs expressed CD90 (99.7%) and CD29 (97.5%). MLT can not only promote the proliferation of ADSCs but also boost their secretory function, especially when ADSCs were pretreated with 5 µM MLT for 3 days, improving the interference effect. After transplantation of autologous ADSCs pretreated with 5 µM MLT, the serum hormone levels and reproductive function were significantly recovered, and the mean counts of primordial follicle increased. At the same time, the expression of SIRT6 was remarkably increased and the expression of NF-κB was significantly decreased in this group.ConclusionsMLT enhances several effects of ADSCs in restoring hormone levels, mean primordial follicle counts, and reproductive capacity in POI mice. Meanwhile, our results suggest that the SIRT6/NF-κB signal pathway may be the potential therapeutic mechanism for ADSCs to treat POI.

Co-overexpression of VEGF and Smad7 improved the therapeutic effects of adipose-derived stem cells on neurogenic erectile dysfunction in the rat model.

Cavernous nerve injury is the main cause of erectile dysfunction (ED) after radical prostatectomy (RP). In our previous study, injection of adipose-derived stem cells (ADSCs) into the cavernosum can repair damaged cavernosum nerves and ED can be restored to a certain extent. In order to improve these therapeutic effects, we evaluated the efficacy of ADSCs co-modified with VEGF and Smad7 in a rat model. SD rats were randomly divided into six groups: a sham surgery group, and the five bilateral cavernous nerve injury (BCNI) groups were injected with ADSC or ADSCs genetically modified by VEGF (ADSC-V), Smad7 (ADSC-S), or VEGF&Smad7 (ADSC-V&S) or phosphate-buffered saline (PBS). The results indicated that the erectile function of the ADSC-V, ADSC-S, and ADSC-V&S groups was significantly recovered, and the erectile function of the ADSC-V&S group was more distinctly recovered as compared to the other groups. The same results are shown in the expression of neuronal nitric oxide synthase and the smooth muscle/collagen ratio of penile tissue comparing the ADSC-V&S group to the ADSC-V and ADSC-S group. These experimental data suggest that ADSCs co-overexpressed with VEGF and Smad7 can significantly improve erectile function after BCNI. This study provides new therapeutic thoughts for ED following RP.

Effect of Adipose-Derived Stem Cell on Collagen Deposition in Nude Mouse Model of Scleroderma

Systemic sclerosis is an autoimmune disease featured by uncontrolled fibrosis and collagen deposition. This study aimed to investigate the impact of adipose-derived stem cells (ADSCs) transplantation on collagen in scleroderma. After establishment of scleroderma model using Bleomycin, the animals received subcutaneous injection of 0.3 ml fat (group B) or 0.3 ml fat+1×106 ADSCs (group C), or 1×106 ADSCs alone (group D). Mice treated with PBS were taken as control group (group A). One month after operation, the skin tissue at injection site was collected for H&amp;E staining, and immunohistochemistry to determine the content of TGF-β1 and type III collagen. Compared to control group, group B, C, and D exhibited improvement in collagen deposition and reduction in TGF-β1 content and type III collagen. Combined graft of fat and ADSCs exerted more significant effect compared to single ADSCs treatment. In conclusion, fat and ADSCs transplantation improves collagen deposition in nude mice with scleroderma and the combined treatment exerts a higher efficacy, suggesting that ADSCs need adipose carrier and microenvironment. These findings provide a novel insight into the treatment of scleroderma.

Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury

Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs.

The Modulatory Effect of Adipose-Derived Stem Cells on Endometrial Polyp Fibroblasts

Endometrial polyps (EPs) are benign overgrowths of the endometrium, with the potential to cause severe complications, ranging from discomfort to inflammation and infertility. Dysfunction of endometrial fibroblasts may be a critical component leading to the development of polyps. Although surgical intervention is the common remedy for severe cases, it comes with drawbacks, including infection, bleeding, and risk of damage to the cervix and adjacent tissues. Adipose-derived mesenchymal stromal cells (ASCs) are at the focus of modern medicine, as key modulators of tissue homeostasis, inflammation, and tissue repair, rendering them prime candidate agents for tissue regeneration and cell-based therapies. In this study, EPs were isolated from patients admitted to the OB/GYN department at the Galilee Medical Center and extracted fibroblasts (endometrial polyp fibroblasts, EPFs) were isolated and characterized. ASCs were isolated from healthy patients. The effect of EPF- and ASC-conditioned media (CM) on polyp-derived fibroblasts was evaluated, in both 2D and 3D assays, as well as on the expression of matrix-related gene expression. Herein, EPFs exposed to ASC-CM exhibited reduced migration, invasion, contraction of hydrogels, and extracellular matrix deposition, compared with those exposed to EPF-CM. Altogether, this study suggests that ASCs may have a modulating effect on fibroblasts involved in forming EPs and may serve as the basis for conservative treatment strategies aimed at treating severe cases of EPs.

Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model.

Adult stem cells have been extensively investigated for tissue repair therapies. Adipose-derived stem cells (ASCs) were shown to improve wound healing by promoting re-epithelialization and vascularization as well as modulating the inflammatory immune response. In this study, we used ex vivo human skin cultured in a six-well plate with trans-well inserts as a model for superficial wounds. Standardized wounds were created and treated with allogeneic ASCs, ASCs conditioned medium (ASC-CM), or cell culture medium (DMEM) supplemented with fetal calf serum (FCS). Skin viability (XTT test), histology (hematoxylin and eosin, H and E), β-catenin expression as well as inflammatory mediators and growth factors were monitored over 12 days of skin culture. We observed only a moderate time-dependent decrease in skin metabolic activity while skin morphology was preserved, and re-epithelialization occurred at the wound edges. An increase in β-catenin expression was observed in the newly formed epithelia, especially in the samples treated with ASC-CM. In general, increased growth factors and inflammatory mediators, e.g., hepatocytes growth factor (HGF), platelet-derived growth factor subunit AA (PDGF-AA), IL-1α, IL-7, TNF-α, and IL-10, were observed over the incubation time. Interestingly, different expression profiles were observed for the different treatments. Samples treated with ASC-CM significantly increased the levels of inflammatory cytokines and PDGF-AA with respect to control, whereas the treatment with ASCs in DMEM with 10% FCS resulted in significantly increased levels of fibroblast growth factor-basic (FGF-basic) and moderate increases of immunomodulatory cytokines. These results confirm that the wound microenvironment can influence the type of mediators secreted by ASCs and the mode as to how they improve the wound healing process. Comparative investigations with pre-activated ASCs will elucidate further aspects of the wound healing mechanism and improve the protocols of ACS application.

Adipose-Derived Stem Cell Sheets Promote Meniscus Regeneration Regardless of Whether the Defect Involves the Inner Half or the Whole Width of the Anterior Half of the Medial Meniscus in a Rabbit Model

To investigate the regenerative effect of adipose-derived stem cell (ADSC) sheets in two different rabbit models of meniscal defects. Forty-two rabbits were randomly divided into two groups: the whole (Group 1) or the inner half (Group 2) of anterior half of the medial meniscus was removed from both knees. The ADSC sheets were transplanted into one knee, whereas in the other knee the meniscal defect was left untreated (self-control). The histological score and expression of genes encoding collagen type I and II (COL1/2), SRY-box transcription factor 9 (SOX9), and aggrecan (ACAN) were compared between the ADSC sheet-treated and untreated menisci at 4 and 12 weeks. The ADSC sheet-treated menisci at 12 weeks were also analyzed immunohistochemically to assess the collagen component. The histological score was significantly higher in the treated side than in the control side at 4 and 12 weeks in both groups (Group 1; P= .016 and .032; Group 2; P= .030 and .016, respectively). All genes evaluated showed significantly higher expression in the treated side than in the control side in both groups, except COL2 and SOX9 at 4 weeks and COL2 at 12 weeks in Group 1, and COL1 in Group 2 at 4 weeks. The ADSC sheet-treated meniscus in Group 1 contained mostly COL1, whereas the Group 2 had less COL1, but was rich in COL2. ADSC sheets can promote meniscal regeneration regardless of whether the defect involves the inner half or whole width of the anterior half of the medial meniscus. However, the collagen component of the ADSC sheet-treated tissue differs depending on the defect site. ADSCs may help meniscal regeneration due to meniscal defects after meniscectomy. This study suggests longer-term follow-up and mechanical analysis as next steps.

Paracrine effects of adipose-derived stem cells in cutaneous wound healing in streptozotocin-induced diabetic rats.

The purpose of this study was to explore the paracrine effects of adipose-derived stem cells (ASCs) on cutaneous wound healing in diabetic rats. The ASCs were isolated and identified by immunofluorescent staining. The ASCs-conditioned medium (ASCs-CM) was harvested. Cell counting kit (CCK)-8 assay, scratch experiments, western blot and quantitative polymerase chain reaction (qPCR) were performed to observe the effects of ASCs-CM on fibroblasts. A full-thickness skin wound diabetic rat model was prepared, using 34 male, Sprague Dawley rats. ASCs-CM or negative-control medium (N-CM) was injected around the wound surface. The existing wound area was measured on days 4, 8, 12 and 16 after the postoperative day, and the wound tissues were collected for immunohistochemical staining and qPCR quantitative study. In this experiment, the isolated cells were characterised as ASCs. The results of CCK-8 assay, cell scratch test, western blot and qPCR showed ASCs-CM could significantly promote the proliferation, migration and differentiation of fibroblasts. Simultaneously, the healing rate of full-thickness skin wounds in diabetic rats was significantly higher in the ASCs-CM group than the N-CM group on days 4, 8, 12 and 16. Immunohistochemical staining and qPCR results showed that the expression of vascular endothelial growth factor (VEGF, days 4 and 8), α-smooth muscle actin (SMA) (days 4 and 16), transforming growth factor (TGF)-β1 (days 4, 8 and 12) were higher in the ASCs-CM group than that of the N-CM group (p<0.05). This experiment demonstrated that ASCs-CM may accelerate wound healing in diabetic rats by promoting the secretion of TGF-β1, VEGF and the proliferation, migration and differentiation of fibroblasts.

Anti-fibrotic effect of adipose-derived stem cells on fibrotic scars.

BACKGROUNDSustained injury, through radiotherapy, burns or surgical trauma, can result in fibrosis, displaying an excessive deposition of extracellular matrix (ECM), persisting inflammatory reaction, and reduced vascularization. The increasing recognition of fibrosis as a cause for disease and mortality, and increasing use of radiotherapy causing fibrosis, stresses the importance of a decent anti-fibrotic treatment.AIMTo obtain an in-depth understanding of the complex mechanisms underlying fibrosis, and more specifically, the potential mechanisms-of-action of adipose-derived stomal cells (ADSCs) in realizing their anti-fibrotic effect.METHODSA systematic review of the literature using PubMed, Embase and Web of Science was performed by two independent reviewers.RESULTSThe injection of fat grafts into fibrotic tissue, releases ADSC into the environment. ADSCs’ capacity to directly differentiate into key cell types (e.g., ECs, fibroblasts), as well as to secrete multiple paracrine factors (e.g., hepatocyte growth factor, basis fibroblast growth factor, IL-10), allows them to alter different mechanisms underlying fibrosis in a combined approach. ADSCs favor ECM degradation by impacting the fibroblast-to-myofibroblast differentiation, favoring matrix metalloproteinases over tissue inhibitors of metalloproteinases, positively influencing collagen organization, and inhibiting the pro-fibrotic effects of transforming growth factor-β1. Furthermore, they impact elements of both the innate and adaptive immune response system, and stimulate angiogenesis on the site of injury (through secretion of pro-angiogenic cytokines like stromal cell-derived factor-1 and vascular endothelial growth factor).CONCLUSIONThis review shows that understanding the complex interactions of ECM accumulation, immune response and vascularization, is vital to fibrosis treatments’ effectiveness like fat grafting. It details how ADSCs intelligently steer this complex system in an anti-fibrotic or pro-angiogenic direction, without falling into extreme dilation or stimulation of a single aspect. Detailing this combined approach, has brought fat grafting one step closer to unlocking its full potential as a non-anecdotal treatment for fibrosis.

Adipose-derived stem cells promote the proliferation, migration, and invasion of oral squamous cell carcinoma cells by activating the Wnt/planar cell polarity signaling pathway.

BackgroundOral squamous cell carcinoma (OSCC) is the most common malignancy of the oral and maxillofacial region. Adipose-derived stem cells (ADSCs) interact with a variety of malignant tumors to promote their proliferation and metastasis. Abnormalities in Wnt/planar cell polarity (PCP) signaling and overactivation of the signaling pathway are considered to be related to the occurrence and development of various malignant tumors. In order to determine whether ADSC can promote tumorigenesis in OSCC and its molecular mechanism, we conducted a series of studies.MethodsThe effect of ADSCs on the occurrence and development of OSCC was studied in vivo and in vitro, and the molecular mechanism was investigated using Western blot and immunofluorescence (IHC) assays.ResultsThe results revealed that ADSCs could promote the proliferation, invasion, and migration of OSCC cells in a dose- and time-dependent manner. With regard to the mechanism, the expression of collagen triple helix repeat-containing protein 1 (CTHRC1) and phospho-c-Jun (p-c-Jun) increased significantly with enhancement of the interaction between ADSCs and OSCC cells, indicating that the Wnt/PCP signaling pathway was overactivated.ConclusionsADSCs promote the pathogenesis of OSCC by activating the Wnt/PCP signaling pathway, suggesting that proteins related to this pathway may be potential therapeutic targets for OSCC.

Adipose-Derived Stem Cell Conditioned Medium and Wound Healing: A Systematic Review.

Adipose-derived stem cells (ASCs) have been growing in popularity for their potential in wound healing and tissue engineering. Stem cell therapies are limited in application, with the need to maintain cell viability and function as well as safety concerns. It has been increasingly reported that the effects of ASCs are predominantly attributable to the paracrine effects of the secreted factors, which can be collected in conditioned medium (CM). The goal of this systematic review was to investigate the effects on wound healing of CM collected from ASC culture. Original articles relevant to ASC-CM and wound healing (in vitro: dermal fibroblast, epidermal keratinocytes, and their equivalent cell lines; in vivo: full-thickness wound models) were included. The agreement level of selections between two investigators was calculated by the kappa scores. And the information concerning to the publications, CM preparation, and its application and effects was extracted and reported in a systematic way and summarized in tables. In total, 121 publications were initially identified through a search of the PubMed/MEDLINE database with a specific search algorithm, and 36 articles were ultimately included after 2 screenings. Nineteen were in vitro studies that met the search criteria and 17 were in vivo studies with or without in vitro data. In summary, based on the included articles, treatment with ASC-CM, to a large extent, resulted in positive effects on wound healing in vitro and in vivo. Modulation of the culture conditions of ASCs producing the CM, including hypoxic conditions, alternative substrates, medium supplementation, as well as genetic modification of cells, favorably promoted the effects of ASC-CM. Finally, a discussion of the future perspectives and therapeutic potential of ASC-CM, which also addresses the limitations of the field, is presented. A limitation of the evidence is the inconsistency in CM preparation methods among included articles. In conclusion, ASC-CM is a promising novel cell-free therapy for wound healing in regenerative medicine and warrants further exploration. Impact Statement This systematic review researched in vitro and in vivo studies regarding therapeutic effects of adipose-derived stem cell (ASC) conditioned medium (CM) on wound healing, generally indicating favorable effects. ASC-CM can avoid safety concerns accompanying stem cell therapies and reduce the cost of treatment. Modulation in the process of ASC culture and CM preparation may promote its therapeutic potential. The limitation and future perspectives of the field of ASC-CM therapy were also presented. ASC-CM may be useful to its future application for a wide range of clinical targets including inflammatory and ischemic diseases.

Therapeutic role of adipose tissue-derived stem cells versus microvesicles in a rat model of cerebellar injury.

Monosodium glutamate (MSG) is a controversial food additive reported to cause negative effects on public health. Adipose stem cells (ASCs) and their derived vesicles (MVs) represent a promising cure for human diseases. This work was planned to compare the therapeutic effects of adipose stem cells and microvesicles in MSG‐induced cerebellar damage. Forty adult healthy male Wister rats were equally divided into four groups: Group I (control group), group II (MSG‐treated), group III (MSG/ASCs‐treated), and group IV (MSG/MVs‐treated). Motor behaviour of rats was assessed. Characterization of ASCs and MVs was done by flow cytometry. The cerebellum was processed for light and electron microscopic studies, and immunohistochemical localization of PCNA and GFAP. Morphometry was done for the number of Purkinje cells in H&E‐stained sections, area per cent of GFAP immune reactivity and number of positive PCNA cells. Our results showed MSG‐induced deterioration in the motor part. Moreover, MSG increases oxidant and apoptotic with decreases of antioxidant biomarkers. Structural changes in the cerebellar cortex as degeneration of nerve cells and gliosis were detected. There were also a decrease in the number of Purkinje cells, an increase in the area per cent of GFAP immune reactivity and a decrease in the number of positive PCNA cells, as compared to the control. Rats treated with ASCs showed marked functional and structural improvement in comparison with MV‐treated rats. Thus, both ASCs and MVs had therapeutic potential for MSG‐induced cerebellar damage with better results in case of ASCs.

Adipose-Derived Stem Cells Therapy for Radiation-Induced Skin Injury.

Radiation-induced skin injuries have been treated with different medical therapies and have shown diverse outcomes. We aim to evaluate the effect of adipose-derived stem cells (ADSCs) therapy on radiation-induced skin injury. We performed a review by querying PubMed, Ovid MEDLINE, and EMBASE databases from inception to April 2020 following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The MeSH terms "adipose-derived stem cells," "wound healing," "radiation," and synonyms in combinations determined our search strategy. Experimental peer-reviewed articles describing the protocol and comparing the results with controls were included. Non-English studies were excluded. Our search recorded a total of 137 articles. Only 8 studies met our inclusion criteria and were included in this review. Five studies evaluated the use of ADSC alone, whereas the others evaluated the efficacy of ADSC seeded in scaffolds. Adipose-derived stem cell-based therapies, either alone or seeded in scaffolds, were shown to improve wound healing in most studies when compared with controls. There is evidence supporting the positive benefits from ADSC-based therapies in radiation-induced skin injury. However, further studies are needed to standardize the method of ADSC extraction, radiation-induced skin injury experimental model, and increase the time of follow-up to evaluate the results accurately.

Effects of Adipose-derived Stem Cells in the Treatment of Knee Osteoarthritis: A Case Report in Brazil's Unified Health System.

Osteoarthritis (OA) can incapacitate the individual to perform their activities of daily living due to pain. This is an important public health issue that worsens worldwide and in Brazil, since the population goes through an aging process, and has caused increased public spending on the monitoring and maintenance of treatments that can last for years and still not be resolutive. Thus, the search for innovative and effective therapies that can reduce costs becomes necessary. In this context, the present study reports the first application of cell therapy with adipose-derived stem cells in the treatment of cases of OA that are refractory to the conservative treatment, performed in the Brazilian Unified Health System (Sistema Único de Saúde, SUS). The evaluation was performed with the application of the Visual Analog Scale (VAS), the Short Form Health Survey (SF-36) and the Western Ontario and McMaster Universities (WOMAC), specifics for OA evaluation, and also an analysis of the synovial fluid (inflammatory cytokines). The cell therapy improved the scores on the WOMAC, SF-36 and EVA, and reduced the inflammatory process. We observed a decrease of 0.73x in the TNF, of 0,71x in IL-1b, of 0,68x in IL-8, and of 0,70x in IL-10. For IL-6, an increase of 1,48x was observed. Therefore, this cell therapy can be considered promising in aiding the management of this disease, since it improved the patient's pain, decrease inflammatory markers, and enabled the return to activities of daily living, which resulted in an improvement in their quality of life.

Effects of Adipose-Derived Stem Cells and Platelet-Rich Plasma Exosomes on The Inductivity of Hair Dermal Papilla Cells.

Objective Hair loss is a prevalent medical problem in both men and women. Maintaining the hair inductivity potential of human dermal papilla cells (hDPCs) during cell culture is the main issue in hair follicle morphogenesis and regeneration. The present study was conducted to compare the effects of different concentrations of exosomes derived from human adipose stem cells (hASCs) and platelet-rich plasma (PRP) on the proliferation, migration and expression of alkaline pholphatase (ALP), versican, and smooth muscle alpha-actin (α-SMA) in human DPCs. Materials and Methods In this experimental study, hDPCs, human hair DPCs and outer root sheet cells (ORSCs) were separated from healthy hair samples. The protocol of exosome isolation from PRP and hASCs comprises serial low speed centrifugation and ultracentrifugation. The effects of different concentrations of exosomes (25, 50, 100 µg/ ml) derived from hASCs and PRP on proliferation (MTS assay), migration (scratch test) and expression of ALP, versican and α-SMA (real time-polymerase chain reaction) in human DPCs were evaluated. Results The flow cytometry analysis of specific cytoplasmic markers showed expression of versican (77%) and α-SMA (60.8%) in DPCs and K15 (73.2%) in ORSCs. According to NanoSight Dynamic Light Scattering, we found the majority of ASCs and PRP-exosomes (ASC-Exo and PRP-Exo) to be 30-150 nm in size. For 100 µg/ml of ASCs-Exo, the expressions of ALP, versican and α-SMA proteins increased by a factor of 1.2, 2 and 3, respectively, compared to the control group. The findings of our experiments illustrated that 100 µg/ml of ASCs-Exo compared to the same concentration of PRP-Exo significantly promote DPC proliferation and migration in culture. ConclusionThis study introduced the potential positive effect of ASC-Exo in increasing the proliferation and survival of DPCs, while maintaining their hair inductivity. Thus, ASCs-Exo possibly provide a new effective procedure for treatment of hair loss.

Adipose-derived stem cells alleviate radiation-induced dermatitis by suppressing apoptosis and downregulating cathepsin F expression

BackgroundRadiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. We previously demonstrated that apoptosis is an important feature of radiation-induced dermatitis and adipose-derived stem cells (ADSCs) are one of the most promising types of stem cells that have a protective effect on acute radiation-induced dermatitis. Cathepsin F (CTSF) is a recently discovered protein that plays an important role in apoptosis. In this study, we investigated whether ADSCs affect chronic radiation-induced dermatitis, and the underlying mechanisms involved.MethodsADSCs were isolated from male Sprague-Dawley (SD) rats and characterized. For in vivo studies, rats were randomly divided into control and ADSC-treated groups, and cultured ADSCs were transplanted into radiation-induced dermatitis model rats. The effects of ADSC transplantation were determined by skin damage scoring, histopathological analysis, electron microscopy, immunohistochemical staining, and western blotting analysis of apoptosis-related proteins. To evaluate the effects of ADSCs in vitro, radiation-induced apoptotic cells were treated with ADSC culture supernatant, and apoptosis-related protein expression was investigated by TUNEL staining, flow cytometry, and western blotting.ResultsIn the in vivo studies, skin damage, inflammation, fibrosis, and apoptosis were reduced and hair follicle and sebaceous gland regeneration were enhanced in the ADSC group compared with the control group. Further, CTSF and downstream pro-apoptotic proteins (Bid, BAX, and caspase 9) were downregulated, while anti-apoptotic proteins (Bcl-2 and Bcl-XL) were upregulated. In vitro, ADSCs markedly attenuated radiation-induced apoptosis, downregulated CTSF and downstream pro-apoptotic proteins, and upregulated anti-apoptotic proteins.ConclusionADSCs protect against radiation-induced dermatitis by exerting an anti-apoptotic effect through inhibition of CTSF expression. ADSCs may be a good therapeutic candidate to prevent the development of radiation-induced dermatitis.