Therapeutic potential of mesenchymal stem cells in liver transplantation: mechanisms, clinical evidence, and translational challenges

Liver transplantation is the standard therapy for end-stage liver disease, but its long-term efficacy is severely compromised by complications such as ischemia-reperfusion injury (IRI), rejection, biliary complications, and adverse effects of immunosuppressants. Mesenchymal stem cells (MSCs), with their immunomodulatory, anti-inflammatory, and prorepair functions, offer new strategies for the prevention and treatment of posttransplant complications. This narrative review summarizes the therapeutic potential and mechanisms of MSCs in mitigating IRI, regulating acute rejection (ACR), treating graft-versus-host disease after liver transplantation (LT-GVHD), and repairing biliary injury, with a focus on their multitarget regulatory network mediated by paracrine effects, mitochondrial transfer, and extracellular vesicles (EVs). Furthermore, this review outlines the characteristic differences among MSCs from various sources, genetic engineering modifications, and optimization strategies such as combination with normothermic machine perfusion (NMP), and analyzes the core challenges in current clinical translation regarding standardization, efficacy heterogeneity, and safety assessment. Finally, drawing on the milestone breakthroughs of MSCs in GVHD treatment, future research directions in the field of liver transplantation are proposed.