The Progress and Promise of Lineage Reprogramming Strategies for Liver Regeneration

The liver exhibits remarkable regenerative capacity. However, the limited ability of primary human hepatocytes to proliferate in vitro, combined with a compromised regenerative capacity induced by pathological conditions in vivo, presents significant obstacles to effective liver regeneration following liver injuries and diseases. Developing strategies to compensate for the loss of endogenous hepatocytes is crucial for overcoming these challenges, and this remains an active area of investigation. Lineage reprogramming, the process of directly converting one cell type into another bypassing the intermediate pluripotent state, has emerged as a promising method for generating specific cell types for therapeutic purposes in regenerative medicine. Here, we discuss the recent progress and emergent technologies in lineage reprogramming into hepatic cells, and their potential applications in enhancing liver regeneration or treating liver disease models. We also address controversies and challenges that confront this field.