Hepatic Stem Cell Compartment: Activation and Lineage Commitment

There is increasingly robust experimental evidence in support of the presence of a pluripotent cell compartment in the liver , , , , , , . This compartment can under certain conditions function as a stem cell compartment and provide the needed progeny for regeneration of the hepatic parenchyma , . In the adult rat, specific conditions can be utilized to induce proliferation of a distinct population of small epithelial cells in the ductal structures of the liver , . These cells, conventionally described as oval cells, are characterized by ovoid nuclei and basophilic cytoplasma , and display features of both bile duct cells and fetal hepatocytes , , . There are three experimental systems, two in the rat and one in the mouse, in which it has been conclusively demonstrated that oval cells are capable of differentiation into hepatocytes , , . The developmental potential of oval cells is, however, not restricted to hepatic lineages. Oval cells can differentiate into intestinal-type epithelia, and have been implicated in the development of pancreatic tissues , , , , ; Fig. 1). The observations that sub-populations of proliferating oval cells phenotypically similar to early hepatoblasts, and that oval cells originate in or around the ductular structures in the portal area, strongly support the notion that the hepatic stem cell compartment resides in these structures , , . Furthermore, present evidence clearly indicates that the hepatic stem cell compartment functions as a facultative stem cell compartment that is activated when the parenchymal cells are unable to proliferate in response to growth stimuli , , , .