S2852 Mesenchymal Stem Cell Therapy in Liver Failure: A Time-Stratified Meta-Analysis Integrating Human Clinical Trials, In Vitro Studies, and Animal Models

Introduction: End-stage liver disease and acute liver failure patients have limited treatment options due to organ shortages and transplant complications. Mesenchymal stem cells show promising regenerative potential. This study analyzes time-dependent MSC outcomes using clinical trials, in-vitro studies, and animal models. Methods: The research team conducted systematic database searches across PubMed, Scopus, Web of Science, Embase, ClinicalTrials.gov, preprint servers and grey literature databases through May 2025 for all liver regenerative therapy studies including in vitro experiments and animal and clinical trials. A meta-analysis evaluated efficacy and safety of MSC therapy. A risk assessment for bias was performed while PRISMA guidelines were followed. Results: The animal experiments showed MSCs operated through immune regulation to eliminate fibrosis while enhancing both survival times and gene therapy approaches restored liver functions in targeted situations. The scaffold-based methods provided temporary liver functionality support to rodent and primate subjects during the short-term. The research conducted with iPSC-derived liver organoids in vitro showed that Wnt signaling and IL-6/STAT3 activation acted as essential pathways for regeneration. The clinical trial meta-analysis results showed MSCs reduced MELD scores by −0.32 (95% CI: −0.55 to −0.10) during the first 4 weeks and by −0.42 (95% CI: −0.82 to −0.02) during the 12-week period and by −0.91 (95% CI: −1.20 to −0.61) during the 24-week assessment but showed no effect at 48 weeks (0.13; 95% CI: −0.48 to 0.74). The pooled effect size was SMD −0.22 (95% CI: −0.33 to −0.12; P < 0.001; I² = 68.3%). The studies showed MSCs elevated albumin levels during all assessment periods extending from 2 weeks (SMD 0.81; 95% CI: 0.50 to 1.11) up to 48 weeks (0.46; 95% CI: 0.37 to 1.30). The combined results showed SMD 0.55 (95% CI: 0.37 to 0.73; P < 0.001; I² = 78.1%). The survival assessment demonstrated statistical significance only at the 48-week point (OR 1.29; 95% CI: 1.03 to 1.60; P = 0.023; I² = 0.0%). Conclusion: This first time-stratified meta-analysis of MSC therapy in liver failure shows MELD and albumin gains (2–24 weeks) and survival benefits at 48 weeks. While generally safe, risks include immune reactions, thrombosis, and reduced efficacy over time. These findings warrant future trials with standardized protocols and adjunctive regenerative strategies to sustain therapeutic benefits.