Ductular hepatocytes. Evidence for a bile ductular cell origin in furan-treated rats

Cholangiolar-like structures composed of biliary epithelial cells and typically a single ductular hepatocytic cell in various stages of maturation appeared in association with an extensive bile ductular reaction within the atrophied right liver lobe of young adult Fischer 344 rats that had been subjected to a severely hepatotoxic treatment with furan. In contrast to normal cholangioles, these cholangiolar-like structures were completely surrounded by a basement membrane, which gave strong immunohistochemical staining reactions for both laminin and type IV collagen. All of the biliary epithelial cells and ductular hepatocytic cells exhibited a strongly positive immunohistochemical staining for gamma-glutamyl transpeptidase and for cytokeratin 8. Cytokeratin 19 was also strongly expressed in all of the biliary epithelial cells, but in just some of the ductular hepatocytic cells, whereas only the latter cells were immunohistochemically positive for albumin and contained peroxisomes in their cytoplasm. Cell junctions were formed between individual ductular hepatocytic cells and adjacent biliary epithelial cells of the same cholangiolar-like structures. In this novel model of severe hepatic injury, the range of cell and nuclear diameters characterizing the ductular hepatocytic cells, together with their phenotypic features, are consistent with a differentiation of rare bile ductular-like cells to transitional ductular cells to more mature ductular hepatocytes.