Isolation, culture, and transplantation of rat hepatocytic precursor (stem-like) cells

From a review of past studies and the report of new studies from our laboratory, this article provides strong evidence to show that WB-F344 (WB) rat liver epithelial cells are stem-like precursor cells for hepatocytes. WB cells are structurally and phenotypically simple epithelial cells that were isolated from the liver of an adult male Fischer 344 rat, under conditions that excluded their origin from hepatocytes in vivo. WB cells express a phenotypic repertory that overlaps, but is distinct from, that of both hepatocytes and bile duct epithelial cells. The complex phenotype of WB cells is compatible with their being embryonic or undifferentiated variants of either hepatocytes or bile duct epithelial cells. When WB cells are tagged genetically with genes for bacterial beta-galactosidase and neomycin resistance (BAG2-WB), they and their progeny can be distinguished from parental WB cells and hepatocytes by the expression of these gene products. Progeny of BAG2-WB cells that were transplanted into the liver parenchyma of syngeneic rats integrated into hepatic plates and acquired the morphological and functional attributes of adjacent host hepatocytes; the progeny of BAG2-WB cells in the liver express albumin, tyrosine aminotransferase, alpha-1-antitrypsin, and transferrin. We also demonstrate that progeny of BAG2-WB cells can be recovered from livers into which they have been transplanted, which may allow the elucidation of alterations in gene expression that accompany their differentiation.