• MSCs are the most extensively studied stem cell type for ESLD, with 25 preclinical and clinical studies reviewed.
• Core mechanisms include differentiation into hepatocyte-like cells, immunomodulation, and inhibition of fibrosis.
• Clinical translation faces challenges such as donor shortages, immune rejection, and high costs, but novel opportunities are emerging.
• MSC therapy offers a promising alternative to liver transplantation by delaying or reversing liver fibrosis or failure.