HEPATIC OV-6 EXPRESSION IN HUMAN LIVER-DISEASE AND RAT EXPERIMENTS - EVIDENCE FOR HEPATIC PROGENITOR CELLS IN MAN

Background/Aims/Methods: Since in raf experiments, activation of proge nitor cells is seen in conditions associated. with hepatocyte injury o r inhibited replication, we compared the activation and fate of human putative progenitor cells in regenerating liver versus chronic cholest atic disease, using immunohistochemistry, rat oval cell marker OV6 and a panel of bile ductular cell markers. We compared the results with d ifferent rat models: the choline-deficient acetylaminofluorene (CDAAF) - and alpha-naphthylisothi-ocyanate (ANIT)-model, using immunohistoche mistry and electron microscopy. Results: In very early stages of human liver regeneration, putative progenitor cells in the vicinity of port al tracts were immunoreactive for OV6, CK7, CK19 and chrom-A. In later stages of regeneration and in chronic cholestasis, reactive bile duct ules (immunoreactive for OV6, CK7, CK19, chrom-A, NCAM) and intermedia te hepatocyte-like cells (immunoreactive for OV6, CK7, chrom-A), becam e apparent, suggesting bidirectional differentiation of the putative p rogenitor cells. In regenerating human liver, intermediate hepatocyte- like cells became more numerous with time and extended far into the lo bule. In advanced cholestasis, intermediate hepatocyte-like cells were less numerous and formed periportal rosettes and small clusters. In t he CDAAF mt model (associated with inhibited hepatocyte replication), but not in the ANIT model, gradual differentiation of oval cells into hepatocytes was seen after stopping the diet. Conclusions: Our results in human liver suggest that reactive ductules and intermediate hepato cyte-like cells originate at least partly from activation and differen tiation of ''progenitor cells''. In regeneration after submassive necr osis, in analogy with what is seen in rat models, differentiation towa rds hepatocytes is more pronounced than in chronic cholestasis.