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 < 0.001). Subgroup analyses performed based on the MSC injection dose (< 1.0 × 10 6 cells, OR = 0.33, 95% CI 0.20-0.56, P < 0.001; 1.0 × 10 6 cells, OR = 0.24, 95% CI 0.16-0.35, P < 0.001) and injection time (< 1 h, OR = 0.24, 95% CI 0.13-0.45, P < 0.001; 1 h, OR = 0.28, 95% CI 0.17-0.46, P < 0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis. Conclusion: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

“…There are other potential therapies for the clinics, such as microbiological guided therapy, including fecal microbiota transplantation (FMT) or probiotic therapy [ 85 – 87 ]. Previous studies of our team have found that the use of stem cells significantly reduces the mortality of septic rats and mice [ 21 , 27 , 74 ]. In future sepsis research, our team will continue to focus on the potential treatment and explore the treatment mechanism.…”

“…Our previous studies also found that ADMSCs attenuate sepsis-related ALI by releasing sTNFR1 [ 21 ]. ADMSCs can alleviate inflammation and oxidative stress [ 22 , 23 ], and many studies have confirmed the therapeutic effect of mesenchymal stem cells (MSCs) in sepsis animal models [ 24 – 27 ]. Furthermore, MSCs can inhibit the MAPK pathway activation during sepsis [ 28 ].…”

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

“…Although MSC therapy was associated with improved outcomes such as faster hemodynamic stabilization, vasodepressor withdrawal, improvement in respiratory failure and decrease in neutropenic period, it did not prevent death from the sepsis related organ failure [101]. However, a meta-analysis study evaluating the efficacy of MSC therapies in animal models of sepsis demonstrated lower mortality rates underlining the potential therapeutic effects of MSCs in sepsis and the need for future studies [102]. On the other hand, EVs as cell-free agents and/or drug carriers may have therapeutic functions in sepsis.…”

Mesenchymal stromal cells for sepsis and septic shock: Lessons for treatment of COVID-19

“…Despite the report of contradictory results, a recent metaanalysis of 29 animal studies, including 1266 animals, demonstrated that MSC therapy was related to a significant lower mortality rate. 32 Moreover, cell tracing studies performed in rodents exhibited that MSCS distribute to a variety of tissues after IV infusion. They were found in the lung early after administration, then in the liver and the spleen.…”

“…However, they did not observe either any beneficial effect of MSCs on organ failures, unlike us. Despite the report of contradictory results, a recent meta‐analysis of 29 animal studies, including 1266 animals, demonstrated that MSC therapy was related to a significant lower mortality rate 32 . Moreover, cell tracing studies performed in rodents exhibited that MSCS distribute to a variety of tissues after IV infusion.…”