Mesenchymal Stem Cell Therapy for Acetaminophen-related Liver Injury: A Systematic Review and Meta-analysis of Experimental Studies In Vivo

Objective: The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen- induced liver injury. Methods: Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE’s risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/ SE 16.0 software. Results: Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) - 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD - 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD - 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05). Conclusion: Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen- related liver injury. The protocol for this meta-analysis was prospectively registered in PROSPERO (Number: CRD42020212677).