Stem cells in liver regeneration and therapy: present and future scope.

The liver has a unique capacity to regenerate. After acute loss of liver mass (i.e. after resection) a sequence of well orchestrated cellular events is initiated which leads to proliferation of mature hepatocytes and biliary cells of the normally quiescent organ to ultimately restore liver function and size within few days. However, in virtually all forms of acute and chronic human liver and biliary diseases, an expansion of ductular reactive cells (DRCs) can be observed. These ductular reactions (DRs) may contain bipotential liver progenitor cells (LPCs) with stem cell properties that reside in a niche close to the terminal bile ducts (Canals of Hering). Adult LPCs are widely believed to serve as an emergency compartment to regenerate both hepatocytes and biliary cells, in case self-duplication of these mature epithelial cells is compromised. Enormous efforts have been undertaken to characterize the cellular identity of adult LPCs and the mechanisms that guide LPC lineage decision and maturation during liver injury as this cellular compartment holds great promise for therapeutical use in acute and chronic liver failure. In this presentation, a critical update on the cellular identity, functional significance, and regenerative capacity of the adult liver progenitor compartment in liver disease will be given. Furthermore, the potential use of adult LPCs as well as alternative stem cell sources for future liver therapy will be discussed.