IMMUNOLOCALIZATION OF OV-6, A PUTATIVE PROGENITOR-CELL MARKER IN HUMAN FETAL AND DISEASED PEDIATRIC LIVER

The existence of progenitor (stem) cells in the human liver remains a matter of debate. In rodent models of hepatocarcinogenesis and injury, oval cells proliferate in the periportal regions of the portal tracts and are suggested to derive from a stem cell compartment, because the y are capable of differentiating into hepatocytes or biliary epithelia l cells. In this study, the rat oval cell marker, OV-6 has been used t o investigate the hypothesis that there are stem cells present in feta l and pediatric human liver. The pattern of OV-6 expression was compar ed with the established adult biliary cell markers human epithelial an tigen-125 (HEA-125) and cytokeratin-19 (CK-19). In normal pediatric li ver (n = 7), bile ducts and ductules were immunostained with CK-19 and HEA-125, whereas OV-6 staining was consistently negative. In fetal ti ssue (n = 10), ductal plate cells, primitive bile ducts, and hepatobla sts were stained with CK-19 and HEA-125 although only some of the duct al plate cells and hepatoblasts were OV-6 positive. In biliary atresia (n = 6) and alpha 1, anti-trypsin deficiency (alpha 1,AT) (n = 4), CK -19 and HEA-125 immunostained ductular proliferative cells that tended to form finely anastomosing ductules, whereas OV-6 staining was found more on discrete cells confined to portal tract margins. Additionally , in diseased liver, OV-6 was strongly positive in hepatocyte lobules with greatest intensity in the periseptal regions. This widespread hep atocyte OV-6 positivity suggests that the antibody may identify cells of a less differentiated phenotype (transitional hepatocytes) that hav e replaced the mature cells. Therefore, it is proposed that in human l iver, OV-6 is recognizing cells with a progenitor stem cell-like pheno type with the capacity to differentiate into OV-6 positive ductular ce lls or lobular hepatocytes.