Hepatic progenitor cells, stem cells, and the biliary epithelium as transit compartment in models of liver injury

Wolf D. Kuhlmann, Peter Peschke


Division of Radiooncology, Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Adult hepatocytes and liver-cell progenitors play a role in restoring liver tissue after injury. For the study of progenitor cells in liver repair, experimental models included (a) surgical removal of liver tissue by partial hepatectomy; (b) acute injury by carbon tetrachloride; (c) acute injury by D-galactosamine (GalN) and N-nitrosomorpholine (NNM); and (d) chemical hepatocarcinogenesis by feeding NNM in low and high doses. Serological and immunohistological detection of alpha-fetoprotein gene expression served to follow pathways of cellular differentiation. In injuries induced by GalN and NNM regeneration of liver occurred through biliary epithelial cells. These biliary epithelial cells, collectively called oval cells, are most probably derived from the canals of Hering. Proliferating bile duct cells reached a level of differentiation with reactivation of foetal genes and significant AFP synthesis signalling a certain degree of retrodifferentiation with potential stemness. Due to the same embryonic origin of bile ducts and hepatocytes, biliary epithelium and its proliferating progeny (oval cells) have a defined role in liver regeneration as a transit and amplification compartment.