Mesenchymal Stromal/Stem Cell-Based Therapies for Liver Regeneration: Current Status and Future Directions

The global burden of acute and chronic liver diseases warrants safe and effective regenerative therapies that can complement or defer liver transplantation. Mesenchymal stromal/stem cells (MSCs) have been recognized as versatile biologics that modulate inflammation, reverse fibrosis, and promote hepatic repair predominantly through paracrine signaling. In hepatic milieu, MSCs act on hepatocytes, hepatic stellate cells, endothelial cells, and immune cell subsets through trophic factors and extracellular vesicles (EVs). Despite demonstrating hepatocyte-like differentiation of MSCs, their in vivo efficacy is primarily attributed to micro-environmental reprogramming rather than durable engraftment. This review covers MSC biology, liver regeneration, and cell-based versus EV therapies, including administration, dosing, quality, and safety. Future directions focus on biomarkers, multi-center trials, and engineered MSC/EV platforms for scalable personalized liver regeneration.