STEM-CELLS AND RAT-LIVER CARCINOGENESIS - CONTRIBUTIONS OF CONFOCAL AND ELECTRON-MICROSCOPY

Microscopic analysis in combination with cytochemistry and immunocytoc hemistry has revealed the presence of four cell types not previously d escribed in the portal area and parenchyma of the liver from an experi mental rodent hepatocarcinogenic rat mode. Within the intrahepatic bil e ductules, which proliferate after administration of chemical carcino gens and partial hepatectomy, small, undifferentiated nonpolarized, no nepithelial cells with a blast-like phenotype and polarized epithelial cells different from the polarized epithelial cells that typically li ne the walls of the bile ductules were Found. In the connective tissue stroma surrounding the bile ductules, nonpolarized epithelial cells w ith hepatocyte phenotype were found. In the parenchyma, subpopulations of bile ductule epithelial cells that established ATPase-positive bil e canalicular structures, including the formation of desmosomes and ti ght junctions, with parenchymal hepatocytes within the hepatic lobule were found. These observations raise the following questions in this m odel. Are there un differentiated progenitor cells with stem cell-like properties within bile ductules? What are the interrelations of the n ewly described cell types with each other, with parenchymal hepatocyte s, with preneoplastic nodules, and with hepatomas? Do the heterogeneou s cell types within the bile ductules, in the surrounding connective t issue, and within the hepatic cords represent intermediate stages of s ingle or multiple cell lineage pathways leading to hepatocyte differen tiation, liver regeneration, and/or preneoplastic nodule formation?.