Mesenchymal stem cell therapy for chronic liver disease: an umbrella review and evidence map of clinical benefits, safety, and evidence certainty

Chronic liver disease (CLD) is a major global public health problem, and treatment options for patients with end-stage disease remain limited. Mesenchymal stem cells (MSCs) are considered a potential therapeutic strategy for CLD. However, the conclusions of existing systematic reviews and meta-analyses are heterogeneous, and a systematic integration of the overall quality of evidence is lacking. This study aimed to systematically evaluate the efficacy and safety of MSCs therapy for CLD through an umbrella review and evidence mapping approach, in order to provide higher-level evidence for clinical decision-making and guideline development. This study was conducted in accordance with the PRISMA statement and was registered in PROSPERO (CRD42025118346). PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched up to February 28, 2026. A total of 25 systematic reviews and meta-analyses were included. The methodological quality of the included studies was assessed using AMSTAR-2, the certainty of evidence was evaluated using the GRADE framework, and an overlapping evidence map was constructed. The results showed that the overall benefit of MSCs on survival outcomes in patients with CLD was limited. A possible signal of survival benefit was observed only in patients with acute-on-chronic liver failure (ACLF) at 12 weeks of follow-up, but the certainty of evidence was low. With respect to all-cause mortality, the results were inconsistent across different follow-up durations and disease subgroups. For important but non-​critical outcomes, MSCs showed relatively consistent improvements in serum albumin and some liver fibrosis-related indicators within 8–24 weeks, with some evidence reaching moderate certainty. Total bilirubin tended to improve in certain populations, but the findings were unstable in the cirrhosis and ACLF subgroups. No clear benefit was observed for coagulation-related indicators such as prothrombin time, prothrombin activity, and international normalized ratio, and prothrombin time even suggested a potential unfavorable trend during long-term follow-up in some ACLF populations. Regarding prognostic scores, MSCs showed a more evident effect on improving the Model for End-Stage Liver Disease score, whereas improvement in the Child-Pugh score was mainly observed in the cirrhosis and combination therapy subgroups. Subgroup analyses by route of administration suggested that hepatic arterial infusion was more likely than intravenous infusion to confer benefits across multiple outcomes, whereas no clear differences were observed among different cell sources. In terms of safety, the available evidence did not suggest that MSCs increased the risk of rash, infection, allergic reactions, or hepatocellular carcinoma, although the certainty of evidence for these outcomes was very low. Current evidence suggests that MSCs therapy for CLD has certain potential in improving albumin levels, some liver fibrosis-related indicators, and certain prognostic scores, but these benefits have not yet been consistently translated into clear and sustained survival advantages. MSCs are more likely to serve as an adjunctive and supportive treatment for CLD rather than an independent therapeutic strategy capable of reversing the prognosis of end-stage disease. High-quality randomized controlled studies with more rigorous designs and longer follow-up are still needed to clarify the optimal timing of intervention, route of administration, and treatment regimen.