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 they are capable of differentiating into hepatocytes or biliary epithelial cells. In this study, the rat oval cell marker, OV-6 has been used to investigate the hypothesis that there are stem cells present in fetal and pediatric human liver. The pattern of OV-6 expression was compared with the established adult biliary cell markers human epithelial antigen-125 (HEA-125) and cytokeratin-19 (CK-19). In normal pediatric liver (n = 7), bile ducts and ductules were immunostained with CK-19 and HEA-125, whereas OV-6 staining was consistently negative. In fetal tissue (n = 10), ductal plate cells, primitive bile ducts, and hepatoblasts were stained with CK-19 and HEA-125 although only some of the ductal plate cells and hepatoblasts were OV-6 positive. In biliary atresia (n = 6) and 1, anti-trypsin deficiency (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 hepatocyte OV-6 positivity suggests that the antibody may identify cells of a less differentiated phenotype (transitional hepatocytes) that have replaced the mature cells. Therefore, it is proposed that in human liver, OV-6 is recognizing cells with a progenitor stem cell-like phenotype with the capacity to differentiate into OV-6 positive ductular cells or lobular hepatocytes.
Department of Biochemistry, University of Birmingham and Liver Units, Queen Elizabeth and Children's Hospital, Birmingham, UK. H.A.Crosby.bcm.bham.ac.uk
H A
HA
Crosby
S G
SG
Hubscher
R E
RE
Joplin
D A
DA
Kelly
A J
AJ
Strain
D000328:Adult; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D001652:Bile Ducts / Q000196:embryology; D001656:Biliary Atresia / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor; D002648:Child; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D007633:Keratins / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology*; D019896:alpha 1-Antitrypsin Deficiency / Q000473:pathology; D000951:Antigens, Neoplasm
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015415:Biomarkers; D014408:Biomarkers, Tumor; D007633:Keratins; C115012:human epithelial antigen-125; D000951:Antigens, Neoplasm; C115011:oval cell marker OV-6