Intramuscular injection of ASCs

Intramuscular injection of ASCs

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Impaired wound healing is a significant medical problem. Recently, cell-based therapy focused on stem cells has been developed to overcome the challenges of defective wound healing. In this study, we aimed to evaluate the effectiveness of adipose-derived stem cells (ASCs) in promoting wound healing, using different techniques for administering them...

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... GFP-positive endothelial cells and adipocytes were identified at post-operative tissue as evidence of direct differentiation of ADSCs. Several other studies also report evidence of differentiation of ADSC into endothelial cells in wound healing models [42][43][44]. ...
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Burn injuries are among the most common types of injuries worldwide, with devastating long-term physical and psychological effects. Recently, adipose-derived stem cells (ADSCs) have shown promise as a potential therapeutic approach for reversing fibrosis, promoting wound healing, and remodeling scars in various types of injuries. ADSCs possess unique features such as multipotency, immunomodulation, and the ability to secrete regenerative factors. These characteristics position them as attractive candidates for enhancing tissue regeneration and reducing inflammation in burn injuries. This overview discusses the current understanding of the biological properties of fat grafts, focusing on ADSCs, in relation to burn injury mechanisms and its clinical manifestations. We examine the role of ADSCs in burn injury and recovery, exploring potential mechanisms of action and future research directions. The aim is to facilitate the clinical application of ADSCs in treating burns and to address the challenges of their clinical use highlighting areas for further research. Level of evidence: Not ratable
... MSCs can be isolated from various sources (such as bone marrow, adipose tissue, and cord blood) and have the ability to promote the development of neighboring cells and regulate the immune system reaction to effectively manage inflammation [10] . BMSCspromote tissue repair by producing growth factors, cytokines, and extracellular matrix, as well as by promoting the migration of other cells [11] . ASCs, which are multipotent cells present in adipose tissue and share similarities with BMSCs, offer the advantage of being easy to obtain and causing minimal donor morbidity, unlike BMSCs that require an invasive procedure and have a low [12] . ...
... Notably, priming or preconditioning of ADSCs with cytokines, hypoxia, or pharmacological drugs in vitro is one of the foremost applicable strategies to improve cell function, survival, and therapeutic potential [127]. However, several limitations, including high cost, induction of immunogenicity, and difficulty in providing good manufacturing practices (GMP) grade quality assurance for clinical application, still need to be addressed in further research [127,128]. ...
Article
Objectives Diabetes mellitus (DM) is a complex metabolic disease that results from impaired insulin secreting pancreatic β-cells or insulin resistance. Although available medications help control the disease, patients suffer from its complications. Therefore, finding effective therapeutic approaches to treat DM is a priority. Adipose Derived Stem Cells (ADSCs) based therapy is a promising strategy in various regenerative medicine applications, but its systematic translational use is still somewhat out of reach. This review is aimed at clarifying achievements as well as challenges facing the application of ADSCs for the treatment of DM, with a special focus on the mechanisms involved.Methods Literature searches were carried out on “Scopus”, “PubMed” and “Google Scholar” up to September 2022 to find relevant articles in the English language for the scope of this review.ResultsRecent evidence showed a significant role of ADSC therapies in DM by ameliorating insulin resistance and hyperglycemia, regulating hepatic glucose metabolism, promoting β cell function and regeneration, and functioning as a gene delivery tool. In addition, ADSCs could improve diabetic wound healing by promoting collagen deposition, inhibiting inflammation, and enhancing angiogenesis.Conclusion Overall, this literature review revealed the great clinical implications of ADSCs for translating into the clinical setting for the treatment of diabetes. However, further large-scale and controlled studies are needed to overcome challenges and confirm the safety and optimal therapeutic scheme before daily clinical application.
... ADSCs were prepared according to previously published methodologies [30,33,41]. The inguinal fat pads of SD rats were minced, washed, and digested with 0.2% type I collagenase (Sigma-Aldrich, St. Louis, MO, USA) for 1 h at 37°C while shaking. ...
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Background: Adipose-derived stem cells (ADSCs) exert immunomodulatory effects in the treatment of transplant rejection. This study aimed to evaluate the effects of ADSCs on the skin graft survival in a human-to-rat xenograft transplantation model and to compare single and multiple injections of ADSCs. Methods: Full-thickness human skin xenografts were transplanted into the backs of Sprague-Dawley rats. The rats were injected subcutaneously on postoperative days 0, 3, and 5. The injections were as follows: triple injections of phosphate-buffered saline (PBS group), a single injection of ADSCs and double injections of PBS (ADSC × 1 group), and triple injections of ADSCs (ADSC × 3 group). The immunomodulatory effects of ADSCs on human skin xenografts were assessed. Results: Triple injections of ADSCs considerably delayed cell-mediated xenograft rejection compared with the PBS and ADSC × 1 groups. The vascularization and collagen type 1-3 ratios in the ADSC × 3 group were significantly higher than those in the other groups. In addition, intragraft infiltration of CD3-, CD4-, CD8-, and CD68-positive cells was reduced in the ADSC × 3 group. Furthermore, in the ADSC × 3 group, the expression levels of proinflammatory cytokine interferon-gamma (IFN-γ) were decreased and immunosuppressive prostaglandin E synthase (PGES) was increased in the xenograft and lymph node samples. Conclusion: This study presented that triple injections of ADSCs appeared to be superior to a single injection in suppressing cell-mediated xenograft rejection. The immunomodulatory effects of ADSCs are associated with the downregulation of IFN-γ and upregulation of PGES in skin xenografts and lymph nodes.
... MSCs can be isolated from various sources (such as bone marrow, adipose tissue, and cord blood) and have the ability to promote the development of neighboring cells and regulate the immune system reaction to effectively manage inflammation [10] . BMSCspromote tissue repair by producing growth factors, cytokines, and extracellular matrix, as well as by promoting the migration of other cells [11] . ASCs, which are multipotent cells present in adipose tissue and share similarities with BMSCs, offer the advantage of being easy to obtain and causing minimal donor morbidity, unlike BMSCs that require an invasive procedure and have a low [12] . ...
... [ DOI: DOI: 10.52547/ibj.3919 ] [ Downloaded from ibj.pasteur.ac.ir on 2023-[10][11][12][13][14][15][16][17][18][19][20][21] ...
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Background: Anaerobes are the causative agents of many wound infections. B. fragilis is the most prevalent endogenous anaerobic bacterium causes a wide range of diseases, including wound infections. This study aimed to assess the antibacterial effect of mouse AD-MSCs encapsulated in CF hydrogel scaffolds on B. fragilis wound infection in an animal model. Methods: Stem cells were extracted from mouse adipose tissue and confirmed by surface markers using flow cytometry analysis. The possibility of differentiation of stem cells into osteoblast and adipocyte cells was also assessed. The extracted stem cells were encapsulated in the CF scaffold. B. fragilis wound infection was induced in rats, and then following 24 h, collagen and fibrin-encapsulated MSCs were applied to dress the wound. One week later, a standard colony count test monitored the bacterial load in the infected rats. Results: MSCs were characterized as positive for CD44, CD90, and CD105 markers and negative for CD34, which were able to differentiate into osteoblast and adipocyte cells. AD-MSCs encapsulated with collagen and fibrin scaffolds showed ameliorating effects on B. fragilis wound infection. Additionally, AD-MSCs with a collagen scaffold (54 CFU/g) indicated a greater effect on wound infection than AD-MSCs with a fibrin scaffold (97 CFU/g). The combined CF scaffold demonstrated the highest reduction in colony count (the bacteria load down to 29 CFU/g) in the wound infection. Conclusion: Our findings reveal that the use of collagen and fibrin scaffold in combination with mouse AD-MSCs is a promising alternative treatment for B. fragilis.
... ASCs were harvested from the inguinal fat of C57BL/6 transgenic mice that express green fluorescent protein (GFP) as previously published [14]. The harvested mouse adipose tissue was extensively washed using sterile phosphate-buffered saline and then finely chopped. ...
... In contrast, the therapeutic potential of intravenous injections of ASCs is related to the paracrine release of cytokines and growth factors, rather than differentiation ability. In a previous study, we compared methods of application (intravenous, intramuscular, and topical) in terms of wound healing in a rodent full-thickness wound defect model; we found no significant differences [14]. Similarly, Hu et al [15] reported that ASCs increased the survival of skin allografts in mice regardless of local or systemic injection. ...
Article
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.
... The question of how to apply ASCs for skin wound healing was addressed by Kim et al. [60]. The researchers compared intravenous injection with intramuscular and topical application (ASCs mixed with a fibrin gel). ...
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Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells.
... Recently, bone tissue engineering (BTE) combined stem cells, growth factors and biomaterial scaffolds to obtain biological substitutes that can reshape craniomaxillofacial morphology, which can better make up for the defects of single application [19][20][21]. Adipose-derived mesenchymal stem cells (ADSCs) are commonly used in BTE, besides they can differentiate into a variety of cell types to improve the functional recovery of different types of damaged tissues [22][23][24][25], their immune regulation has attracted increasing attention. These cells play therapeutic roles in many immune diseases by secreting anti-inflammatory cytokines and growth factors that counteract inflammatory factors and can effectively regulate the immune response caused by biomaterial implantation [26][27][28]. ...
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Objectives Bone defects caused by diseases and trauma are usually accompanied by inflammation, and the implantation of biomaterials as a common repair method has also been found to cause inflammatory reactions, which affect bone metabolism and new bone formation. This study investigated whether exosomes from adipose-derived stem cells (ADSC-Exos) plays an immunomodulatory role in traumatic bone defects and elucidated the underlying mechanisms. Methods ADSC-Exos were loaded by a biomaterial named gelatine nanoparticles (GNPs), physical and chemical properties were analysed by zeta potential, surface topography and rheology. A rat model of skull defect was used for our in vivo studies, and micro-CT and histological staining were used to analyse histological changes in the bone defect area. RT-qPCR and western blotting were performed to verify that ADSC-Exos could regulate M1/M2 macrophage polarization. MicroRNA (miRNA) array analysis was conducted to determine the miRNA expression profiles of ADSC-Exos. After macrophages were treated with a miR-451a mimic, miR-451a inhibitor and ISO-1, the relative expression of genes and proteins was measured by RT-qPCR and western blotting. Results In vivo, micro-CT and histological staining showed that exosome-loaded GNPs (GNP-Exos) hydrogel, with good biocompatibility and strong mechanical adaptability, exhibited immunomodulatory effect mainly by regulating macrophage immunity and promoting bone tissue healing. Immunofluorescence further indicated that ADSC-Exos reduced M1 marker (iNOS) expression and increased M2 marker (CD206) expression. Moreover, in vitro studies, western blotting and RT-qPCR showed that ADSC-Exos inhibited M1 macrophage marker expression and upregulated M2 macrophage marker expression. MiR-451a was enriched in ADSC-Exos and targeted macrophage migration inhibitory factor (MIF). Macrophages treated with the miR-451a mimic showed lower expression of M1 markers. In contrast, miR-451a inhibitor treatment upregulated the expression of M1 markers and downregulated the expression of M2 markers, while ISO-1 (a MIF inhibitor) treatment upregulated miR-451a expression and downregulated M1 macrophage marker expression. Conclusion GNP-Exos can effectively regulate bone immune metabolism and further promote bone healing partly through immune regulation of miR-451a, which may provide a therapeutic direction for bone repair.
... Swelling ratios of the nanocomposite DEX/GLY and Lignin@DEX/GLY were examined by previously reported protocol [35][36][37]. To determine the humidity absorption capacity of the DEX/GLY and Lignin@DEX/GLY nanoparticles, 0.2 g of dry powder material of DEX/GLY and Lignin@DEX/GLY nanoparticles were submerged in 40 mL of saline with the pH of 7.2 at RT for 18 h to attain optimum ratio of swelling, and extracted, gradually pushed between Whatmann filter paper, and balanced. ...
Article
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Lignin-loaded nanoparticles are versatile nanomaterials that may be used in wound healing properties. The current study describes a wound dressing formulation focused on Lignin-loaded dextran/glycol (DEX/GLY) nanoparticles. The Lignin-loaded dextran/glycol membranes were fabricated using Lignin solutions inside the dextran/glycol medium. The influence of various experimental conditions on dextran/glycol nanoparticle formations were examined. The sizes of dextran/glycol and Lignin-loaded dextran/glycol nanoparticles were examined through the HR-SEM. Moreover, the efficacy antibacterial activity of dextran/glycol and Lignin-loaded dextran/glycol nanoparticles was evaluated against the microorganisms gram-positive and negative. Furthermore, we observed the in vivo wound healing of wounds in skin using a mice model over a 14 days period. In this difference to the wounds of untreated mouse, quick healing was observed in the Lignin-loaded dextran/glycol nanoparticles-treated wounds with fewer injury. These results specify that Lignin-loaded dextran/glycol nanoparticles-based dressing material could be a ground-breaking nanomaterial having wound repair and implantations potential required for wound injury in anorectal surgery model, which was proven using an animal model. Graphic Abstract
... Topical application provides cell metabolism, migration, and differentiation. Moreover, it can stimulate extracellular matrix secretion and tissue regeneration [102,103]; therefore, shortening treatment time and improving the survival rate of transplants, with better clinical application value [104][105][106]. Although most topical applications were used in allogeneic stem cell therapy, other studies' results were consistent with our systemic review and meta-analysis [78,107]. ...
Article
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Lower extremity chronic wounds (LECWs) commonly occur in patients with diabetes mellitus (DM) and peripheral arterial disease (PAD). Autologous stem cell therapy (ASCT) has emerged as a promising alternative treatment for those who suffered from LECWs. The purpose of this study was to assess the effects of ASCT on LECWs. Two authors searched three core databases, and independently identified evidence according to predefined criteria. They also individually assessed the quality of the included randomized controlled trials (RCTs), and extracted data on complete healing rate, amputation rate, and outcomes regarding peripheral circulation. The extracted data were pooled using a random-effects model due to clinical heterogeneity among the included RCTs. A subgroup analysis was further performed according to etiology, source of stem cells, follow-up time, and cell markers. A total of 28 RCTs (n = 1096) were eligible for this study. The pooled results showed that patients receiving ASCT had significantly higher complete healing rates (risk ratio (RR) = 1.67, 95% confidence interval (CI) 1.28–2.19) as compared with those without ASCT. In the CD34+ subgroup, ASCT significantly led to a higher complete healing rate (RR = 2.70, 95% CI 1.50–4.86), but there was no significant difference in the CD34− subgroup. ASCT through intramuscular injection can significantly improve wound healing in patients with LECWs caused by either DM or critical limb ischemia. Lastly, CD34+ is an important cell marker for potential wound healing. However, more extensive scale and well-designed studies are necessary to explore the details of ASCT and chronic wound healing.