Differentiation processes of oval cells into hepatocytes: proposals based on morphological and phenotypical traits in carcinogen-treated hamster liver.

Hepatic stem cells participate in the recovery process of liver with severe injury or impaired hepatocyte regeneration. Oval cells (an oval-shaped liver cell population newly emerging from the portal or periportal zones following severe hepatic cellular damage) are believed to be the progeny of liver stem cells and precursor cells of both hepatocytes and bile duct cells. An attempt was made to define the differentiation processes of hepatic oval cells into mature hepatocytes in hamsters fed a choline-deficient diet and treated with diethylnitrosamine and 2-acetyl aminofluorene, on the basis of histopathological, electron microscopical, histochemical and immunohistochemical characterization of hepatic cell components. Two putative differentiation pathways of oval cells toward mature hepatocytes are proposed, namely (1) the differentiation of ductular-like oval cells via ductular/acinar-type hepatocytes, and (2) the differentiation of individual oval cells via small hepatocytes. Those proposals were strongly supported by consistent immunoreactivity of the cells for OV-6, an oval cell marker, and differential expression patterns for CK19 and PAS-positive cytoplasmic glycogen granules.