Liver progenitor cell-driven liver regeneration

The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver diseases. Hepatocyte-driven liver regeneration that involves the proliferation of preexisting hepatocytes is a primary regeneration mode. On the other hand, liver progenitor cell (LPC)-driven liver regeneration that involves dedifferentiation of biliary epithelial cells or hepatocytes into LPCs, LPC proliferation, and subsequent differentiation of LPCs into hepatocytes is a secondary mode. This secondary mode plays a significant role in liver regeneration when the primary mode does not effectively work, as observed in severe liver injury settings. Thus, promoting LPC-driven liver regeneration may be clinically beneficial to patients with severe liver diseases. In this review, we describe the current understanding of LPC-driven liver regeneration by exploring current knowledge on the activation, origin, and roles of LPCs during regeneration. We also describe animal models used to study LPC-driven liver regeneration, given their potential to further deepen our understanding of the regeneration process. This understanding will eventually contribute to developing strategies to promote LPC-driven liver regeneration in patients with severe liver diseases. A deeper understanding of the biology of liver progenitor cells (LPCs) could give clinicians more effective tools for reversing the effects of liver disease. LPCs are precursors of the liver cells known as hepatocytes, and naturally appear when the tissue is injured or diseased. Juhoon So, Donghun Shin and colleagues at the University of Pittsburgh, USA, have reviewed the current state of knowledge of LPC biology. They explore the mechanisms by which LPCs are generated and activated in response to trauma. These molecular pathways could offer useful drug targets.The authors also point out that excessive LPC activity can promote liver damage and tumorigenesis. As a consequence, any regenerative medicine approach based on LPCs must be coupled with effective strategies for promoting the efficient maturation of these cells into healthy hepatocytes.