Liver regeneration in rats with retrorsine-induced hepatocellular injury proceeds through a novel cellular response

The adult rodent Liver contains at least two recognized populations of cell s with stem-like properties that contribute to liver repair/regeneration un der different pathophysiological circumstances: (i) unipotential committed progenitor cells (differentiated hepatocytes and biliary epithelial cells) and (ii) multipotential nonparenchymal progenitor cells (oval cells). In re trorsine-induced hepatocellular injury the capacity of fully differentiated rat hepatocytes to replicate is severely impaired and massive proliferatio n of oval cells does not occur. Nevertheless, retrorsine-exposed rats can r eplace their entire liver mass after 2/3 surgical partial hepatectomy throu gh the emergence and expansion of a population of small hepatocyte-like pro genitor cells that expresses phenotypic characteristics df fetal hepatoblas ts, oval cells, and fully differentiated hepatocytes, but differ distinctly from each type of cell. The activation, proliferation, and complete regene ration of normal liver structure from small hepatocyte-like progenitor cell s have not been recognized in other models of liver injury characterized by impaired hepatocyte replication, We suggest that the selective emergence a nd expansion of small hepatocyte-like progenitor cells observed in. the ret rorsine model reflect a novel mechanism of complete liver regeneration in t he adult rat. Furthermore, we suggest that these cells may represent a nove l progenitor cell population that (i) responds to liver deficit when the re plication capacity of differentiated hepatocytes is impaired, (ii) expresse s an extensive proliferative capacity, (iii) can give rise to large numbers of progeny hepatocytes, and (iv) can restore tissue mass.