The Efficacy of Mesenchymal Stem Cell Therapy in Large Animal Models of Acute Liver Failure: A Meta-Analysis

Mesenchymal stem cells (MSCs) show therapeutic effects for acute liver failure (ALF), as demonstrated in small animal models of ALF, which showed improved survival and liver function. Nevertheless, small animal models are limited by their simplified immune systems and lower pathophysiological complexity, which prevent them from fully capturing the key features of human ALF. Large animal models offer better physiological similarity; however, the effectiveness of MSC therapy on large animal models of ALF, such as pigs and monkeys, remains unclear. In this study, we performed a meta-analysis to comprehensively evaluate the therapeutic effect and safety of MSC therapy in large animal models of ALF. A comprehensive search was conducted across PubMed/Medline, Web of Science, Embase, and the Cochrane Library for studies published prior to 3 March 2025. Of the 609 identified studies, 13 were included, with the majority showing a low or unclear risk of bias. The results of the meta-analysis indicated that MSC therapy was associated with a higher survival rate and lower levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in large animal models with ALF, compared with the control groups. Subgroup analyses showed efficacy in both pig and monkey models. Furthermore, they showed that bone marrow-derived mesenchymal stem cells and the deep vein transplantation route were each linked to a significantly higher survival rate and to lower ALT and AST levels after treatment in pigs with ALF. Additionally, a dose of (3.0-3.3) × 10⁶/kg was associated with a significantly higher survival rate, as well as a lower AST level after treatment. In summary, the findings suggest MSC therapy is a safe and potential therapeutic option for large animals with ALF, although randomized controlled trials (RCTs) are needed for further validation.