SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
This article is part of the Research TopicFriend or foe? - The role of macrophages and neutrophils in liver pathologiesView all 3 articles
Mesenchymal Stem Cell–Derived Small Extracellular Vesicles (sEVs) as a Therapy for Sepsis-Related Liver Injury: Evidence from a Systematic Review and Meta-Analysis
Provisionally accepted
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Abstract Background: Sepsis-induced liver injury (SILI) is critical in the progression of high morbidity and mortality associated with sepsis which ends in hepatic dysfunction and multi-organ failure. Mesenchymal stem cell–derived small extracellular vesicles (MSC-sEVs) are valued for their anti-inflammatory and regenerative potential as favorable strategy. The present systematic review and meta-analysis aimed to assess the effect of MSC-sEVs in rodent models with SILI. Methods: A comprehensive systematic search was carried out in the PubMed, Web of Science, Embase, Scopus, and the Cochrane Library through April 2025. All published studies in relation to the the effect of MSC-sEVs in rodent models were included. Pooled standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for study outcomes. Results: Ten studies were included in the present study. MSC-sEVs significantly reduced ALT (SMD = -2.49, 95% CI: -3.37, -1.62), AST (SMD = -1.97, 95% CI: -3.32, -0.62), reduced pro-inflammatory cytokines (TNF-α: SMD = -5.23, 95% CI: -7.05, - 3.41; IL-6: SMD = -5.00, 95% CI: -7.36, -2.64), and increased survival (OR = 6.11, 95% CI: 2.20-16.98; P = 0.001). No significant effects were observed for IL-10 (SMD = - 3.39, 95% CI: -9.47, 2.69) or NLR (SMD = -0.65, 95% CI: -1.75, 0.45). Subgroup analyses illustrated that overall efficacy of treatment may vary dependent to source of sEVs, route of administration, and induction methods. Conclusions: MSC-sEVs is able to improve liver function, inflammation, and survival rate in rodent sepsis model. These findings suggest that MSC-sEVs could be considered as therapeutic strategy for sepsis. These findings not only quantify the effect size of MSC-sEVs but also provide methodological insights for preclinical studies and guide future translational research.
Keywords: Mesenchymal stem cell-derived small extracellular vesicles, Sepsis, liver injury, Animal Models, Meta- analysis
Received: 17 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Pan, Xu, Shui, Hong, Lu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yan Pan, yanpan810@gmail.com
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