Adipose-derived Stem Cell Therapy Research Articles

Adipose-derived stem cells in diabetic foot care: Bridging clinical trials and practical application.

Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

Mechanical stretch preconditioned adipose-derived stem cells elicit polarization of anti-inflammatory M2-like macrophages and improve chronic wound healing.

Transplantation of adipose-derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti-inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties invitro. MS triggers the secretion of macrophage colony stimulating factor (M-CSF) from ASCs, a chemokine that is linked to anti-inflammatory M2-like macrophages polarization. When the MS-ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS-ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.

Adipose-derived Stem Cells Therapy for Moderate Chronic Obstructive Pulmonary Disease in Adult Subjects: A Phase III Randomized, Multicenter Trial: RESPIRE Protocol

Introduction: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and has a prevalence of 11.7%. Current treatment focuses on reducing symptoms and exacerbations, as no definitive intervention exists. Regenerative treatments such as mesenchymal stem cell (MSCs) therapy have shown promise in preclinical and clinical studies. This article presents a study protocol to evaluate the efficacy of adipose-derived (AD) MSCs therapy in improving FEV-1 in COPD patients. Methods: A phase III, multicenter, randomized, double-blind, placebo-controlled study is proposed to test the clinical safety and efficacy of AD-MSC therapy in patients with COPD. The population is subjects with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 (50%≤FEV1<80% predicted) and Group D (two exacerbations or one hospitalization and mMRC>2 or CAT>10). This study aims to evaluate the improvement of FEV1 from baseline to 90 days after AD-MSC infusion. The primary outcome is FEV1-improvement (%) over the baseline for the treatment and placebo groups, assessed on study day 90 vs. baseline (day 0). For the primary outcome, the statistical analysis will use the Mann-Whitney U test to analyze the FEV1 for the treatment and control groups at 90 days against the baseline. Discussion: Aside from symptomatic relief, there is a growing demand for a curative treatment for COPD. The potential of novel AD-MSCs therapies for COPD improvement is currently in early development. Preclinical, phase I, and a few phase II studies for AD-MSCs as a COPD treatment have proven optimistic results. This phase III, randomized, multicenter trial proposes evaluating an alternative treatment for this condition that may improve lung function.

In vivo confocal microscopy evaluation of infiltrated immune cells in corneal stroma treated with cell therapy in advanced keratoconus

PurposeThis study investigates immune cell (ICs) infiltration in advanced keratoconus patients undergoing autologous adipose-derived adult stem cell (ADASC) therapy with recellularized human donor corneal laminas (CL).MethodsA prospective clinical trial included fourteen patients divided into three groups: G-1, ADASCs; G-2, decellularized CL (dCL); and G-3, dCL recellularized with ADASCs (ADASCs-rCL). Infiltrated ICs were assessed using in vivo confocal microscopy (IVCM) at 1,3,6, and12 months post-transplant.ResultsInfiltrated ICs, encompassing granulocytes and agranulocytes, were observed across all groups, categorized by luminosity, structure, and area. Stromal ICs infiltration ranged from 1.19% to 6.62%, with a consistent increase in group-related cell density (F = 10.68, P < .0001), independent of post-op time (F = 0.77, P = 0.511); the most substantial variations were observed in G-3 at 6 and 12 months (2.0 and 1.87-fold, respectively). Similarly, significant size increases were more group-dependent (F = 5.76, P < .005) rather than time-dependent (F = 2.84, P < .05); G-3 exhibited significant increases at 6 and 12 months (3.70-fold and 2.52-fold, respectively). A lamina-induced shift in IC size occurred (F = 110.23, P < .0001), primarily with 50–100 μm2 sizes and up to larger cells > 300μm2, presumably macrophages, notably in G-3, indicating a potential role in tissue repair and remodeling, explaining reductions in cells remnants < 50μm2.ConclusionsADASCs-rCL therapy may lead to increased IC infiltration compared to ADASCs alone, impacting cell distribution and size due to the presence of the lamina. The findings reveal intricate immune patterns shaped by the corneal microenvironment and highlight the importance of understanding immune responses for the development of future therapeutic strategies.

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review.

The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars. We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews' reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate. Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate. AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.

Interleukin 4 improved adipose-derived stem cells engraftment via interacting with fibro/adipogenic progenitors in dystrophic mice

Adipose-derived stem cells (ADSC) therapy shows promise as an effective treatment for dystrophinopathy. Fibro-/adipogenic progenitors (FAPs) play an essential role in the myogenesis of muscle satellite cells and contribute to muscle fibrosis and adipocyte infiltration. The interleukin 4 (IL-4) pathway acts as a switch that regulates the functions of FAPs. The interaction between FAPs and engrafted cells remains unclear. In this study, we used a co-culture system to investigate possible crosstalk between the FAPs of dystrophic mice and ADSC overexpressing IL4 (IL4-ADSC) and control ADSC. Systemic transplantation of IL4-ADSC and control ADSC in dystrophic mice was conducted for 16 weeks, after which motor function and molecular improvements were evaluated. Overexpression of IL4 in ADSC significantly promoted myogenesis in vitro, increasing the expression of Pax7, Myogenin, and MyHC. Co-culture indicated that although myoblasts derived from control ADSC promoted adipogenic and fibrogenic differentiation of FAPs, FAPs did not significantly affect myogenesis of ADSC-derived myoblasts. However, overexpression of IL4 in ADSC inhibited their myotube-dependent promotion of FAPs differentiation on the one hand and promoted FAPs to enhance myogenesis on the other. Dystrophic mice administered with IL4-ADSC-derived myoblasts displayed significantly better motor ability, more engrafted cells showing dystrophin expression, and less muscle fibrosis, intramuscular adipocytes, and macrophage infiltration than mice administered control-ADSC-derived myoblasts. In conclusion, IL4 activation enhanced the therapeutic potential of ADSC transplantation in dystrophic mice, possibly by improving the myogenesis of IL4-ADSC and altering the crosstalk between engrafted stem cells and resident FAPs.

Platelet-Rich Plasma (PRP) and Adipose-Derived Stem Cell (ADSC) Therapy in the Treatment of Genital Lichen Sclerosus: A Comprehensive Review.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis mostly localized in the genital area, characterized by vulvar alterations that can severely impact a patient's quality of life. Current treatment modalities often provide incomplete relief, and there is a need for innovative approaches to manage this condition effectively. Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) have emerged as potential regenerative therapies for LS, offering promising results in clinical practice. This comprehensive review explores the utilization of PRP and ADSC therapy in the treatment of genital LS, highlighting their mechanisms of action, safety profiles, and clinical outcomes. PRP is a blood product enriched in growth factors and cytokines, which promotes tissue regeneration, angiogenesis, and immune modulation. ADSC regenerative potential relies not only in their plasticity but also in the secretion of trophic factors, and modulation of the local immune response. Numerous studies have reported the safety of PRP and ADSC therapy for genital LS. Adverse events are minimal and typically involve mild, self-limiting symptoms, such as transient pain and swelling at the injection site. Long-term safety data are encouraging, with no significant concerns identified in the literature. PRP and ADSC therapy have demonstrated significant improvements in LS-related symptoms, including itching, burning, dyspareunia, and sexual function. Additionally, these therapies enable many patients to discontinue the routine use of topical corticosteroids. Several studies have explored the efficacy of combining PRP and ADSC therapy for LS. In combination, PRP and ADSCs seem to offer a synergistic approach to address the complex pathophysiology of LS, particularly in the early stages. The use of PRP and ADSC therapy for genital lichen sclerosus represents a promising and safe treatment modality. These regenerative approaches have shown significant improvements in LS-related symptoms, tissue trophism, and histological features. Combination therapy, which harnesses the synergistic effects of PRP and ADSCs, is emerging as a preferred option, especially in early-stage LS cases. Further research, including randomized controlled trials and long-term follow-up, is warranted to elucidate the full potential and mechanisms of PRP and ADSC therapy in the management of genital LS. These regenerative approaches hold great promise in enhancing the quality of life of individuals suffering from this challenging condition.

Efficacy and feasibility of stromal vascular fraction containing adipose derived stem cells obtained from freshly prepared lipoaspirate for treatment of complex anorectal fistulas- A novel approach

BackgroundAnal fistulas are relatively common. Despite diverse treatment modalities and tremendous advance and optimization of surgical approaches, considerable recurrence and high failure rates are not uncommon especially after surgery for complex anal fistulas. Therefore, autologous adipose-derived stem cell therapy for the treatment of complex perianal fistula can be an innovative and promising option with potential high cure rate and long-term healing. AimTo assess the efficacy and feasibility intralesional administration of stromal vascular fraction containing autologous, adipose-derived stem cells prepared from fresh lipoaspirate for management of complex and recurrent anal fistula. MethodsTotally, 28 patients with complex perianal fistulas were enrolled in this prospective case-series study from March 2018 and August 2022. They were 22 male and 6 females patient) with 38.8 years average ages (ranges from 26 to 54 years). All patients were assigned to receive intralesional injection with autologous freshly prepared adipose-derived stem cells from lipoaspirate suction in a concentration of 1 × 107 cell/ml. The healing of fistulas, confirmed by clinical assessment and magnetic resonance imaging was evaluated at week 6 weeks, 12 weeks and 6 months after treatment. If no evidence of healing was not seen at 6 weeks, a second dose of same concentration was administered. In addition to fistula healing, adverse effect (functional outcomes), complications and procedure safety were also evaluated. ResultsThe overall healing rate of fistulas treated by injection of ADSCs was 60.7% (17/28), while healing rate after first injection was 50% (14/28) and after second injection was 30% (3/10).Three patients were lost after first injection. During the follow up period of 6 months none of the patients who showed complete healing, recorded relapse of their fistulas (recurrence 0%). Further, none of the patients recorded complications or adverse reactions related to stem cell therapy during the study and none of them had worsening fecal incontinence during follow-up period. Postoperative pain assessed by.VAS score was significantly low (>3). Fecal continence assessed by Wexner score of all patients was not changed or affected. ConclusionsInjection of complex perianal fistulas by freshly prepared autologous ADSCs could be a valid and effective treatment modality. It is safe, feasible and minimally invasive procedure that lacks the risk of injury to anal sphincter complex, unlike other surgical procedures that endanger the anal continence.Further, second dose of ADSCs injection could improve the rate of healing, without adding adverse effects.

Adipose-Derived Stem Cell Therapy in Hypertrophic and Keloid Scars: A Systematic Review of Experimental Studies

Introduction: Hypertrophic and keloid scars are abnormal tissue growth that can be disfiguring, for which the available treatment has not yielded consistent results. Therefore, this study aimed to evaluate the capability of Adipose tissue-derived stem cell (ADSC) therapy in treating these scars. Methods: A literature search was conducted on PubMed, Scopus, Cochrane Library, and Web of Science from inception until July 2022. We included experimental studies that evaluated ADSCs as a therapy for hypertrophic and keloid scars in both in-vivo and in-vitro models. Results: Our findings extracted from 12 included studies demonstrated that ADSCs have a promising potential in reducing collagen deposition, proliferation, and migration rates of fibroblast, decreasing gene/protein expression of scar-related molecules including levels of TGF-β1 and lowering intracellular signal pathway-related molecules of hypertrophic and keloid scars in both models. However, no significant difference ( P &gt; .05) was found in the hypertrophic scar in-vitro models in terms of DCN gene expression. Conclusion: Ultimately, the current studies included in this systematic review support the use of ADSCs to alleviate hypertrophic and keloid scars.

ADIPOSE-DERIVED STEM CELL THERAPY ON NON-COMMUNICABLE DISEASE: A SYSTEMATIC REVIEW

The increasing number of non-communicable diseases demands practical therapy innovations, including adipose-derived stem cell application. This study aimed to analyze the effectiveness of adipose stem cell therapy on non-communicable disease patients. The method used in this study was a systematic review according to PRISMA 2020 guidelines. The database search was done on PubMed, Google Scholar, Proquest, and the EBSCO host database between 2016 and 2021. ROBINS-I tool and RoB-2 were used to assess the risk of bias in the clinical trial study. The first literature search identified a total of 2615 articles. After exclusion for some reason, 6 articles were included in this systematic review study. A total of five studies were included in this study. Based on the risk of bias assessment of the included studies, it was found that all studies had a low risk of bias in all domains. This study showed that the efficacy of adipose-derived stem cell therapy was inconsistent; however, the results were promising. In addition, the results showed that adipose-derived stem cell therapy was safe without significant side effects. Further study was needed to identify therapeutic strategies based on Evidence-based Medicine (EBM).

Advancements in adipose-derived stem cell therapy for skin fibrosis

Pathological scarring and scleroderma, which are the most common conditions of skin fibrosis, pathologically manifest as fibroblast proliferation and extracellular matrix (ECM) hyperplasia. Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling, causing an exaggerated and prolonged wound-healing response. The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects. Currently, a promising and relatively low-cost treatment has emerged-adipose-derived stem cell (ASC) therapy as a branch of stem cell therapy, including ASCs and their derivatives-purified ASC, stromal vascular fraction, ASC-conditioned medium, ASC exosomes, etc., which are rich in sources and easy to obtain. ASCs have been widely used in therapeutic settings for patients, primarily for the defection of soft tissues, such as breast enhancement and facial contouring. In the field of skin regeneration, ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis. The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review, as well as their new applications in the treatment of skin fibrosis. Although the long-term effect of ASC therapy is still unclear, ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.

Comparable Effects on Healing between Autologous Diabetic Adipose-Derived Stem Cells and Allogeneic Normal Counterparts.

Adipose-derived stem cell (ASC) therapy is considered a promising strategy for improving impaired wound healing, especially in diabetics. Although the therapeutic potential of allogeneic ASCs from healthy donors is naturally limited, that of autologous ASCs from diabetic patients is questionable. The aim of this study was to investigate the impact of diabetic ASCs in the treatment of diabetic wounds. Diabetic ASCs (DMA) and nondiabetic ASCs were isolated from db/db and C57BL/6J mice, and characterized by immunocytochemistry, proliferation, differentiation, and gene expression assays. The effects of both ASCs on healing were investigated using 36 male 10- to 12-week-old db/db mice. Wound size was measured semiweekly until day 28, and histologic and molecular analyses were performed at day 14. Both ASCs had fibroblast-like morphology and were CD44 + /CD90 + /CD34 - /CD45 - at passage 4. Compared with nondiabetic ASCs in vitro, DMA proliferative capability was restored by passage 4 ( P > 0.05). Although DMA osteogenesis was attenuated ( P < 0.01), both ASCs had similar adipogenesis and expressions of PPARγ/LPL/OCN/RUNX2 ( P > 0.05). In vivo experiments showed that, compared with phosphate-buffered saline control, both ASCs are comparable in improving wound healing ( P < 0.0001), angiogenesis ( P < 0.05), epithelial cell proliferation ( P < 0.05), and granulation tissue formation ( P < 0.0001). In both in vitro and in vivo murine models, DMAs have shown a comparable therapeutic capacity to normal ASCs in promoting diabetic wound healing by improving angiogenesis, reepithelialization, and granulation tissue formation. These results support clinical applications of autologous ASCs in diabetic wound treatments. This work has particular surgical relevance as it highlights a theoretical and clinical pathway to use diabetic patients' own ASCs to treat their wounds, bypassing any concerns of cross-host sourcing issues in regenerative medicine.

Insulin modified Decellularized Adipose Tissue/Tremella Polysaccharide hydrogel loaded with ADSCs for skin wound healing

Full-thickness skin wounds still represent a challenge for clinical treatment. Adipose-derived stem cells (ADSCs) therapy is a promising approach to achieve efficient healing in skin wounds. The excellent cell scaffold can promote proliferation, differentiation and paracrine of ADSCs in wound microenvironment, and is a key factor in ADSCs application. Herein, we first prepared the composite hydrogel with decellularized adipose tissue (DAT) and tremella polysaccharide (TPS), and loaded insulin (INS) into the DAT/TPS composite hydrogel (DAT/TPS-gel) to fabricate an efficient carrier for ADSCs in treating skin wound. Our study showed that INS modified DAT/TPS-gel (INS-DAT/TPS-gel) can promote the proliferation, differentiation and paracrine of ADSCs. INS-DAT/TPS-gel laden with ADSCs (ADSCs/INS-DAT/TPS-gel) effectively facilitated the skin wound healing in SD rats. These findings indicated that INS-DAT/TPS-gel was an effective scaffold for ADSCs transplantation, and ADSCs/INS-DAT/TPS-gel provides a potential strategy for the treatment of skin wounds.

Tumor necrosis factor-α inhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation.

Cartilage tissue engineering is a promising strategy for treating cartilage damage. Matrix formation by adipose-derived stem cells (ADSCs), which are one type of seed cell used for cartilage tissue engineering, decreases in the late stage of induced chondrogenic differentiation in vitro, which seriously limits research on ADSCs and their application. To improve the chondrogenic differentiation efficiency of ADSCs in vitro, and optimize the existing chondrogenic induction protocol. Tumor necrosis factor-alpha (TNF-α) inhibitor was added to chondrogenic culture medium, and then Western blotting, enzyme linked immunosorbent assay, immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B (NF-κB) signaling pathway. In this study, we found that the levels of TNF-α and matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs. TNF-α then bound to its receptor and activated the NF-κB pathway, leading to a decrease in cartilage matrix synthesis and secretion. Blocking TNF-α with its inhibitors etanercept (1 μg/mL) or infliximab (10 μg/mL) significantly restored matrix formation. Therefore, this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs, and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

Adipose-Derived Stem Cells (ADSCs) Supplemented with Hepatocyte Growth Factor (HGF) Attenuate Hepatic Stellate Cell Activation and Liver Fibrosis by Inhibiting the TGF-β/Smad Signaling Pathway in Chemical-Induced Liver Fibrosis Associated with Diabetes.

Liver fibrosis can develop on the background of hyperglycemia in diabetes mellitus. However, xenobiotic-related factors may accelerate diabetes-associated liver fibrosis. In this study, we aimed to assess the antfibrotic effect of ADSC and HGF therapy and to establish the cellular and molecular mechanisms through in vitro and in vivo experiments. In vitro, TGF-β1-activated hepatic stellate cells (HSCs) were cocultured with ADSCs or HGF, and the expression of several fibrosis markers was investigated. The antifibrotic effect of the ADSCs, HGF, and ADSCs supplemented with HGF was further assessed in vivo on diabetic mice with liver fibrosis experimentally induced. In vitro results showed the inhibition of HSC proliferation and decrease in fibrogenesis markers. Coadministration of ADSCs and HGF on diabetic mice with liver fibrosis enhanced antifibrotic effects confirmed by the downregulation of Col I, α-SMA, TGF-β1, and Smad2, while Smad7 was upregulated. Moreover, stem cell therapy supplemented with HGF considerably attenuated inflammation and microvesicular steatosis, decreased collagen deposits, and alleviated liver fibrosis. In conclusion, the HGF-based ADSC therapy might be of interest for the treatment of liver fibrosis in diabetic patients, consecutive aggression exerts by different environmental factors.

S191 Efficacy and Safety of Adipose-Derived Stem Cell Therapy for the Treatment of Complex Perianal Fistula Not Associated With Crohn’s Disease: A Systematic Review and Meta-Analysis

Introduction: Given the high recurrence rate and the risk of fecal incontinence with surgical options, Injection of adipose tissue-derived stem cells (ASC) has been arising as a novel method for treating complex perianal fistulas (CPAF). Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of ASC in the management of CPAF not associated with Crohn’s disease. Methods: We systematically searched Medline and Embase databases through April 20, 2022, for all studies that assessed the efficacy and safety of ASC for the treatment of CPAF not associated with Crohn’s disease. We excluded patients with rectovaginal fistulas and perianal fistulas associated with Crohn’s disease. Our primary outcome was the complete closure. The secondary outcomes included overall nonserious adverse events (NSAE), serious adverse events (SAE), and perianal abscess rate. All meta-analyses were conducted using a random-effect model. The publication bias was assessed by Egger’s test. Results: Ten studies (eight clinical trials and two observational studies) with 271 patients were included in the pooled analysis. Eight studies used autologous stem cells, one used allogeneic stem cells, and one did not report the source of stem cells. The mean age of the patients was 43.7 years. The follow-up period ranged from 3 months to 2 years. The pooled complete closure rate was 59.7% (95% confidence interval (CI): 0.46-0.73, Figure 1A). On subgroup analysis based on country of origin, six studies with 213 patients were conducted in European countries, and four studies with 58 patients were conducted in non-European countries. The complete closure rate was higher in European countries than non-European countries, 64.1% vs. 52.6%. Eight studies reported overall NSAEs with the pooled NSAE rate of 22.5% (95% CI: 0.11-0.34, Figure 1B). Seven studies reported SAEs with the pooled SAE rate of 1.7% (95% CI: 0.001-0.034, Figure 1C). Seven studies reported the perianal abscess rate with a pooled perianal abscess rate of 7.1% (95% CI: 0.016-0.125, Figure 1D). No evidence of publication bias was found (Egger’s test: P=0.36). Conclusion: Our meta-analysis demonstrated that ASC is a promising therapeutic option for CPAF not associated with Crohn’s disease with a clinically adequate efficacy and low rate of adverse events. However, more studies with larger sample sizes are needed to provide a definitive assessment of the effectiveness of ASCs for CPAF not associated with Crohn’s disease.Figure 1

Application of Free Skin Flap Transplantation in Skin Malignant Tumor Resection.

One of the most important surgical approaches for restoring cutaneous abnormalities caused by tumor resection is the insertion of a skin flap. Flap transplantation has been used to cover and fill different deficiencies after tumor removal. However, distal necrosis is among the most prevalent postsurgical consequences for skin flaps, particularly when treating large regions. Blood circulation failure causes flap necrosis, which may lead to serious problems, particularly in patients undergoing body cavity reconstruction following tumor excision. ADSCs (adipose-derived stem cells) are a kind of stem cell separated from the adipose tissue that has multilineage differentiation, simple availability, high proliferation capability, and self-renewal capabilities. This paper uses human adipose-derived stem cell (ADSC) therapy for skin flap transplantation in skin malignant tumor resection. ADSC-based therapy is an applicable technique for assisting flap transplantation. The isolation of ADSC is performed using different trypsin concentrations, and then, the population doubling time is determined. The isolated ADSCs are differentiated and then employed for the skin flap model. The performance of the suggested method is analyzed using various assays. The usage of adipose-derived stem cells to boost the vitality of the skin flaps proved successful.

Clinical Application of Adipose Derived Stem Cells for the Treatment of Aseptic Non-Unions: Current Stage and Future Perspectives-Systematic Review.

Fracture non-union is a challenging orthopaedic issue and a socio-economic global burden. Several biological therapies have been introduced to improve traditional surgical approaches. Among these, the latest research has been focusing on adipose tissue as a powerful source of mesenchymal stromal cells, namely, adipose-derived stem cells (ADSCs). ADSC are commonly isolated from the stromal vascular fraction (SVF) of liposuctioned hypodermal adipose tissue, and their applications have been widely investigated in many fields, including non-union fractures among musculoskeletal disorders. This review aims at providing a comprehensive update of the literature on clinical application of ADSCs for the treatment of non-unions in humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Only three articles met our inclusion criteria, with a total of 12 cases analyzed for demographics and harvesting, potential manufacturing and implantation of ADSCs. The review of the literature suggests that adipose derived cell therapy can represent a promising alternative in bone regenerative medicine for the enhancement of non-unions and bone defects. The low number of manuscripts reporting ADSC-based therapies for long bone fracture healing suggests some critical issues that are discussed in this review. Nevertheless, further investigations on human ADSC therapies are needed to improve the knowledge on their translational potential and to possibly achieve a consensus on their use for such applications.

A new strategy for stem cells therapy for erectile dysfunction: Adipose-derived stem cells transfect Neuregulin-1 gene through superparamagnetic iron oxide nanoparticles.

PurposeOur previous studies showed that nanotechnology improves derived adipose-derived stem cells (ADSCs) therapy for erectile dysfunction (ED). In this study, the Neuregulin-1(NRG1) gene was transfected into ADSCs with superparamagnetic iron oxide nanoparticles (SPION) further to improve the therapeutic effect of ADSCs on ED.Materials and MethodsADSCs were isolated from epididymal adipose tissue of Sprague–Dawley rats. The optimal concentration of PEI-SPION (SPION modified with polyethyleneimine) was selected to construct the gene complex. After electrostatic binding of PEI-SPION and DNA, a PEI layer was wrapped to make the PEI-SPION-NRG1-PEI gene transfection complex. Different groups were set up for transfection tests. Lipo2000 transfection reagent was used as the control. PEI-SPION-NRG1-PEI in the experimental group was transfected under an external magnetic field.ResultsWhen the concentration of PEI-SPION was 10 µg/mL, it had little cytotoxicity, and cell activity was not significantly affected. PEI-SPION-NRG1-PEI forms positively charged nanocomposites with a particle size of 72.6±14.9 nm when N/P ≥8. The PEI-SPION-NRG1-PEI gene complex can significantly improve the transfection efficiency of ADSCs, reaching 26.74%±4.62%, under the action of the external magnetic field. PCR and Western blot showed that the expression level of the NRG1 gene increased significantly, which proved that the transfection was effective.ConclusionsPEI-SPION can be used as a vector for NRG1 gene transfection into ADSCs. PEI-SPION-NRG1-PEI packaging has the highest transfection efficiency under the external magnetic field than the other groups. These findings may provide a new strategy for ADSCs therapy for ED.

Human adipose-derived stem cells in fibrin glue carrier modulate wound healing phases in rats

Cell-based therapy using human adipose-derived stem cells (ADSCs) is a new approach for enhancing wound healing. Therefore, in this study, we aimed to evaluate the immunomodulatory effect and wound healing process based on xenografted human ADSCs in a fibrin glue matrix carrier during the wound healing process in a full-thickness excisional model in rats. Two excisional wounds were made in the dorsum of 60 rats using a dermatological punch (1.5 cm diameter), and the rats were randomly assigned to three groups: control (untreated group), FG (topical treatment of both wounds with fibrin glue), and ADSC+FG (topical treatment of both wounds with 2.0 × 10 5 ADSCs in fibrin glue carrier). On the 2nd, 7th, 14th, and 21st days after the wounding surgical process, re-epithelialization was assessed by imaging the skin/wound/scar, and samples were harvested for histomorphometric analyses (quantification of inflammatory cells, blood vessels, fibroblasts, and collagen); biochemical quantification of myeloperoxidase (neutrophil), N-acetylglucosaminidase (macrophage), hydroxyproline (total collagen), and glycosaminoglycans; immunohistochemistry to detect IL-10 and IL-17; and western blot analysis of TNF-α, TGF-β1, and VEGF. ADSC+FG therapy stimulated the anti-inflammatory response up to the 7th day, where the IL-10 levels were higher compared with the control group. This treatment induced angiogenesis, fibroblast proliferation, and collagen formation faster than the other treatments to enhance re-epithelialization. ADSC and FG therapy could be suitable for modulating the inflammatory response and enhancing re-epithelialization, as well as the formation of new blood vessels during wound healing.