Therapeutic potential of MSCs and their exosomes in hepatic Ischaemia-Reperfusion injury: a systematic review and meta-analysis of rodent studies.

Abstract

OBJECTIVE: This meta-analysis comprehensively evaluates the therapeutic efficacy and mechanisms of mesenchymal stem cells (MSCs) and their exosomes in rodent models of hepatic ischemia-reperfusion injury (HIRI), providing preclinical support for future clinical translation. METHODS: In accordance with the PRISMA guidelines, we systematically searched PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for studies published from inception to January 13, 2025, and identified 64 eligible studies. Risk of bias was evaluated using the SYRCLE tool, and Review Manager 5.4.1 was employed for meta-analysis, calculating SMD and 95%CI. Primary outcomes included liver function (ALT/AST), histopathological scores (Suzuki's score, necrotic area ratio), inflammatory cytokines (TNF-&#x3b1;), and apoptosis markers (c-caspase 3). RESULTS: MSCs and their exosomes significantly ameliorated HIRI. In the 60-minute ischemia group, ALT (SMD&#x2009;=&#x2009;3.49, P < .00001) and AST (SMD&#x2009;=&#x2009;3.86, P < .00001) decreased, along with lower Suzuki scores (SMD&#x2009;=&#x2009;3.12), necrotic area ratios (SMD&#x2009;=&#x2009;3.56), and TNF-&#x3b1; levels (SMD&#x2009;=&#x2009;2.83). In the 90-minute group, ALT (SMD&#x2009;=&#x2009;4.09, P < .00001) and AST (SMD&#x2009;=&#x2009;3.78, P < .00001) were also reduced. Mechanistically, MSCs exert therapeutic effects through antioxidative, anti-inflammatory, anti-apoptotic, and pro-regenerative pathways. Considerable heterogeneity (I2 = 52-86%) was observed, likely due to variations in dosage (1&#x2009;&#xd7;&#x2009;105-1&#x2009;&#xd7;&#x2009;109 cells), administration routes (intravenous/portal vein), and reperfusion durations (3-24&#x2009;hours). Genetic modifications (e.g., HO-1 overexpression) further enhanced therapeutic outcomes. CONCLUSION: MSCs and their exosomes mitigate HIRI through multi-target mechanisms but requires standardized protocols. Future studies should prioritize large-animal validation and translational research to facilitate precision clinical application.