Wolf D. Kuhlmann and Peter Peschke
Division of Radiooncology, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany
Experimental models for the study of progenitor cells in liver repair included (a) surgical removal of liver tissue by partial hepatectomy; (b) acute injury by carbontetrachloride; (c) acute injury by D-galactosamine (GalN) and N-nitrosomorpholine (NNM); and (d) chemical hepatocarcinogenesis by feeding NNM in low and high doses. The detection of alpha-fetoprotein gene expression served to follow pathways of cellular differentiation. Stem cells were not required in models of surgical removal of parenchyma and in carbon tetrachloride intoxication. In contrast, regeneration of liver occurred through biliary epithelial cells in injuries induced by GalN and NNM. 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 fetal genes and significant AFP synthesis signalling a certain degree of retrodifferentiation with potential stemness.