Mesenchymal stem cell therapy for end-stage liver disease: adversity and opportunity

End-stage liver disease (ESLD) is one of the predominant diseases contributing to high morbidity and mortality worldwide, with etiologies including alcoholic liver disease, viral hepatitis, non-alcoholic fatty liver disease, and metabolic-associated liver disease. Currently, liver transplantation remains the only effective treatment, however, its clinical application is significantly limited by donor shortages, immune rejection, and high medical costs. Among the five types of stem cells that have been experimentally applied to liver diseases, mesenchymal stem cells (MSCs) have emerged as the most extensively studied, with the largest number of experimental and clinical research platforms worldwide. This review compiles findings from 25 preclinical and clinical studies on MSCs in the treatment of ESLD, aiming to elucidate the core mechanisms of action and then outline both the challenges in MSC clinical translation and the novel opportunities arising from cutting-edge research.