Origin and structural evolution of the early proliferating oval cells in rat liver

We have analyzed the histological changes in rat liver after 2-acetylaminof luorene (AAF) administration. The data demonstrate that AAF-induced oval ce lls were preferentially generated by proliferation of the terminal biliary ductules that we suggest constitute the primary hepatic stem cell niche. Th e oval cells formed ductular structures, representing an extension of the c anals of Hering. This histological organization provides continuous bile dr ainage of the hepatocytes and uninterrupted blood flow in the sinusoids. Th e oval cell ductules are surrounded by a continuous basement membrane that is intermittently disrupted by processes of stellate cells that form direct cell-cell contact with the oval cells. Although both AAF treatment and bil e duct Ligation results In proliferation of biliary epithelial cells, the m echanism(s) responsible for the proliferation of the biliary epithelium see ms to differ in the two models. in contrast to the biliary proliferation st imulated by bile ligation, AAF-induced oval cell proliferation as well as t he capacity of these cells to differentiate into hepatocytes, bile epitheli al cells and possibly other cell lineages can be blocked by administration of dexamethasone.