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Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

ABSTRACT: BACKGROUND:Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies. METHODS:A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS:Twenty-nine animal studies, including 1266 animals, were identified. None of the studies was judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22-0.38, P?

SUBMITTER: Sun XY

PROVIDER: S-EPMC7268531 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

Sun Xue-Yi XY Ding Xian-Fei XF Liang Huo-Yan HY Zhang Xiao-Juan XJ Liu Shao-Hua SH Bing-Han Duan Xiao-Guang XG Sun Tong-Wen TW

Stem cell research & therapy 20200603 1

<h4>Background</h4>Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies.<h4>Methods</h4>A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, ...[more]

PMID: 32493435

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Project description:BackgroundParaquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.MethodsThe electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.ResultsEleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.ConclusionMSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.

Project description:BackgroundDespite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; however, this approach remains controversial. The aim of this systematic review and meta-analysis is to assess the potential efficacy of SC therapy for PAH.MethodsThe Medline, EMBASE, Cochrane Library, and Web of Science databases were searched from inception to August 12, 2018. Preclinical studies that evaluated the use of SC therapy for PAH were included. The primary outcome was pulmonary haemodynamics, as assessed by measurement of the right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and/or mean right ventricle pressure (mRVP). The secondary outcomes included the weight ratio of the right ventricle to the left ventricle plus septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW), the percentage of pulmonary arteriole area index (WA), and/or the percentage of medial wall thickness of the pulmonary arteriole (WT). The quality of outcomes was evaluated using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool. The inverse-variance method with random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Statistical analysis was performed with STATA 14.0.ResultsTwenty-eight eligible articles (722 animals) were included. SC therapy reduced the pooled WMDs (95% CIs) of RVSP, mPAP, mRVP, RV/LV+S, RV/BW, WA, and WT for animals with PAH, with values of - 14.12 (- 14.63, - 13.61), - 11.86 (- 12.35, - 11.36), - 17.33 (- 18.10, - 16.56), - 0.10 (- 0.10, - 0.09), 0.23 (0.21, 0.24), - 13.66 (- 15.71, - 11.62), and - 7.96 (- 7.99, - 7.93), respectively.ConclusionsSC therapy is effective for PAH in preclinical studies. These results may help to standardise preclinical animal studies and provide a theoretical basis for clinical trial design in the future.Systematic review registrationPROSPERO ( http://www.crd.york.ac.uk/PROSPERO ).

Project description:Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM). Lung alveolarization was the primary outcome. We used random effects models for data analysis and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened 990 citations; 25 met inclusion criteria. All used hyperoxia-exposed neonatal rodents to model BPD. MSCs significantly improved alveolarization (Standardized mean difference of -1.330, 95% confidence interval [CI -1.724, -0.94, I2 69%]), irrespective of timing of treatment, source, dose, or route of administration. MSCs also significantly ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis, and apoptosis. Similarly, MSC-CM significantly improved alveolarization, angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear risk of bias and incomplete reporting in the primary studies highlights nonadherence to reporting standards. Overall, safety and efficacy in other species/large animal models may provide useful information for guiding the design of clinical trials. Stem Cells Translational Medicine 2017;6:2079-2093.

Project description:BackgroundA skin flap is one of the most critical surgical techniques for the restoration of cutaneous defects. However, the distal necrosis of the skin flap severely restricts the clinical application of flap surgery. As there is no consensus on the treatment methods to prevent distal necrosis of skin flaps, more effective and feasible interventions to prevent skin flaps from necrosis are urgently needed. Stem therapy as a potential method to improve the survival rate of skin flaps is receiving increasing attention.MethodsThis review followed the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. Twenty studies with 500 animals were included by searching Web of Science, EMBASE, PubMed, and Cochrane Library databases, up until October 8, 2020. Moreover, the references of the included articles were searched manually to obtain other studies. All analyses were conducted using Review Manager V.5.3 software.ResultsMeta-analysis of all 20 studies demonstrated stem cell treatment has significant effects on reducing necrosis of skin flap compared with the control group (SMD: 3.20, 95% CI 2.47 to 3.93). Besides, subgroup analysis showed differences in the efficacy of stem cells in improving the survival rate of skin flaps in areas of skin flap, cell type, transplant types, and method of administration of stem cells. The meta-analysis also showed that stem cell treatment had a significant effect on increasing blood vessel density (SMD: 2.96, 95% CI 2.21 to 3.72) and increasing the expression of vascular endothelial growth factor (VEGF, SMD: 4.34, 95% CI 2.48 to 6.1).ConclusionsThe preclinical evidence of our systematic review indicate that stem cell-based therapy is effective for promoting early angiogenesis by up regulating VEGF and ultimately improving the survival rate of skin flap. In summary, small area skin flap, the administration method of intra-arterial injection, ASCs and MSCs, and xenogenic stem cells from humans showed more effective for the survival of animal skin flaps. In general, stem cell-based therapy may be a promising method to prevent skin flap necrosis.

Dataset Information

Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

Publications

Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

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