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Efficacy assessment of mesenchymal stem cell transplantation for burn wounds in animals: a systematic review.

ABSTRACT: BACKGROUND:Clinically, severe burns remain one of the most challenging issues, but an ideal treatment is yet absent. Our purpose is to compare the efficacy of stem cell therapy in a preclinical model of burn wound healing. METHODS:Research reports on mesenchymal stem cells (MSCs) for burn wound healing were retrieved from 5 databases: PubMed, Embase, MEDLINE, Web of Science, and the Cochrane Library. The primary outcomes reported in this article include the un-healing rate of the wound area, the closure rate, and the wound area. Secondary outcomes included CD-31, vascular density, interleukin (IL)-10, thickness of eschar tissue, vascular endothelial growth factor (VEGF), and white blood cell count. Finally, a subgroup analysis was conducted to explore heterogeneity that potentially impacted the primary outcomes. A fixed-effects model with a 95% confidence interval (CI) was performed when no significant heterogeneity existed. Otherwise, a random-effects model was used. All data analysis was conducted by using Engauge Digitizer 10.8 and R software. RESULTS:Twenty eligible articles were finally included in the analysis. Stem cell therapy greatly improved the closure rate (2.00, 95% CI 0.52 to 3.48, p?=?0.008) and compromised the wound area (-?2.36; 95% CI -?4.90 to 0.18; p?=?0.069) rather than the un-healing rate of the wound area (-?11.10, 95% CI -?32.97 to 10.78, p?=?0.320). Though p was 0.069, there was a trend toward shrinkage of the burn wound area after stem cell therapy. Vascular density (4.69; 95% CI 0.06 to 9.31; p?=?0.047) and thickness of eschar tissue (6.56, 95% CI 1.15 to 11.98, p?=?0.017) were also discovered to be significantly improved in the burn site of stem cell-treated animals. Moreover, we observed that animals in the stem cell group had an increased white blood cell count (0.84, 95% CI 0.01 to 1.66, p?=?0.047) 5?days post treatment. Other indicators, such as VEGF (p?=?0.381), CD-31 (p?=?0.335) and IL-10 (p?=?0.567), were not significantly impacted. CONCLUSIONS:Despite limited data from preclinical trials, this meta-analysis suggests that stem cell therapy is curative in decreasing the burn wound area and provides some insights into future clinical studies of stem cell therapy for burns.

SUBMITTER: Yi H

PROVIDER: S-EPMC7456061 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Efficacy assessment of mesenchymal stem cell transplantation for burn wounds in animals: a systematic review.

Yi Hanxiao H Wang Yang Y Yang Zhen Z Xie Zhiqin Z

Stem cell research & therapy 20200828 1

<h4>Background</h4>Clinically, severe burns remain one of the most challenging issues, but an ideal treatment is yet absent. Our purpose is to compare the efficacy of stem cell therapy in a preclinical model of burn wound healing.<h4>Methods</h4>Research reports on mesenchymal stem cells (MSCs) for burn wound healing were retrieved from 5 databases: PubMed, Embase, MEDLINE, Web of Science, and the Cochrane Library. The primary outcomes reported in this article include the un-healing rate of the ...[more]

PMID: 32859266

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Project description:BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT.MethodsStudies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4.ResultsSix randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) - 1.20, p = 0.04; nRCTs: SMD - 0.54, p = 0.04) and platelet engraftment (RCTs: SMD - 0.60, p = 0.04; nRCTs: SMD - 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p < 0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT.ConclusionMSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.

Project description:Current wound healing models generally employ full-thickness or irregular split wounds. Consequently, assessing the type of healing at varying wound depths and determining the deepest level at which wounds can regenerate has been a challenge. We describe a wound model that allows assessment of the healing process over a continuous gradient of wound depth, from epidermal to full-thickness dermal loss. Further, we investigate whether green fluorescent protein-labeled bone marrow mesenchymal stem cells (BM-MSCs/GFP) transplantation could regenerate deeper wounds that might otherwise lead to scar formation. A wound gradient was created on the back of 120 Sprague Dawley rats, which were randomized into the BM-MSCs/GFP and control group. These were further subdivided into 6 groups where terminal biopsies of the healing wounds were taken at days 1, 3, 5, 7, 14, and 21 post-operatively. At each observed time point, the experimental animals were anesthetized and photographed, and depending on the group, the animals euthanized and skin taken for rapid freezing, haemotoxylin and eosin staining, and vascular endothelial growth factor (VEGF) immunohistochemistry. We found the deepest layer to regenerate in the control group was at the level of the infundibulum apex, while in the BM-MSCs/GFP group this was deeper, at the opening site of sebaceous duct at hair follicle in which had the appearance of normal skin and less wound contraction than the control group (P value less than .05). The expression of VEGF in BM-MSCs/GFP group was higher than that in control group (P value less than .05). The number of vessels increased from 2.5 ± 0.2/phf of control group to 5.0 ± 0.3/phf of BM-MSCs/GFP (P value less than .05). The progressively deepening wound model we described can identify the type of wound repair at increasing depths. Further, topical transplantation of BM-MSCs/GFP significantly improved regeneration of deeper wounds from infundibulum apex (maximum depth of control group regeneration) to the opening site of sebaceous duct at hair follicle level.

Project description:BackgroundStem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an autoimmune-based disorder, but previous studies have not presented a comprehensive view of its effect on treatment of T1DM.MethodologyAfter registration of the present systematic review and meta-analysis in the PROSPERO, a search was done according to the Cochrane guidelines for evaluation of clinical trials to find eligible clinical trials that investigated the effect of SCT on T1DM (based on ADA® diagnostic criteria) from PubMed, Web of science, Scopus, etc, as well as registries of clinical trials from January 1, 2000, to September 31, 2019. A search strategy was designed using MeSH and EM-tree terms. Primary outcome included the changes in the insulin total daily dose (TDD) (U/kg) level, and secondary outcomes included the changes in the HbA1c, c-peptide, and adjusted HbA1c levels. The Q Cochrane test and I2 statistic were performed to assess the heterogeneity and its severity in primary clinical trials. The Cochrane ROB was used to determine risk of bias, and Cochrane Handbook for Systematic Reviews of Interventions was used in the full text papers. The meta-analysis was accomplished in the STATA software, and the results were shown on their forest plots. Confounders were evaluated by the meta-regression test.ResultsA total of 9452 studies were electronically screened, and 35 papers were included for data extraction. The results of this review study showed that 173 (26.5%) diabetic patients experienced insulin-free period (from 1 to 80 months), and 445 (68%) showed reduction in TDD of insulin after the SCT. Combination of hematopoietic stem cell (HSC) with mesenchymal stem cell (MSC) transplantation were significantly associated with improvement of the TDD (SMD: - 0.586, 95% CI: - 1.204/- 0.509, I2: 0%), HbA1c (SMD: - 0.736, 95% CI: - 1.107/- 0.365, I2: 0%), adjusted HbA1c (SMD: - 2.041, 95% CI: - 2.648/- 1.434, I2: 38.4%), and c-peptide (SMD: 1.917, 95% CI: 0.192/3.641, I2: 92.5%) on month 3 of follow-up, while its association had a growing trend from 3 to 12 months after the transplantation. Considering severe adverse events, HSC transplantation accompanied with conditioning could not be suggested as a safe treatment.ConclusionMost of the clinical trials of SCT in T1DM were single arm. Although meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy.RecommendationBased on the results of this meta-analysis, the MSC and its combination with HSC could be considered as "Safe Cell" for SCT in T1DM. Furthermore, to evaluate the SCT efficacy, calculation of insulin TDD (U/kg/day), AUC of c-peptide, and adjusted HbA1c are highly recommended.

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Efficacy assessment of mesenchymal stem cell transplantation for burn wounds in animals: a systematic review.

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Efficacy assessment of mesenchymal stem cell transplantation for burn wounds in animals: a systematic review.

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