title: Isolation of EpCAM(+)/CD133 (-) hepatic progenitor cells.
abstract: Progenitor cell-derived hepatocytes are critical for hepatocyte replenishment. Therefore, we established a line of human hepatic progenitor (HNK1) cells and determined their biological characteristics for experimental and therapeutic applications. HNK1 cells, isolated from human noncirrhotic liver samples with septal fibrosis, showed high expression of the hepatic progenitor cell (HPC) markers EpCAM, CK7, CK19, alpha-fetoprotein (AFP), CD90 (Thy1), and EFNA1. Expression of CD133 was very low. Ductular reactions at the periphery of cirrhotic nodules were immunohistochemically positive for these HPC markers, including EFNA1. Sodium butyrate, a differentiation inducer, induced hepatocyte-like morphological changes in HNK1 cells. It resulted in down-regulation of the hepatic progenitor cell markers EpCAM, CK7, CK19, AFP, and EFNA1 and up-regulation of mature hepatocyte markers, including albumin, CK8, and CK18. Furthermore, sodium butyrate treatment and a serial passage of HNK1 cells resulted in enhanced albumin secretion, ureagenesis, and CYP enzyme activity, all of which are indicators of differentiation in hepatocytes. However, HNK1 cells at passage 50 did not exhibit anchorage-independent growth capability and caused no tumors in immunodeficient mice, suggesting that they had no spontaneous malignant transformation ability. From this evidence, HNK1 cells were found to be EpCAM(+)/CD133(-) hepatic progenitor cells without spontaneous malignant transformation ability. We therefore conclude that HNK1 cells could be useful for experimental and therapeutic applications.
authors.affiliation: Division of Gastroenterology and Hepatology, Departments of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju, 561-712, Korea.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Hao
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Goung-Ran
authors.initials: GR
authors.lastname: Yu
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Kim
authors.forename: Yong-Gon
authors.initials: YG
authors.lastname: Cho
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D020148:Butyric Acid / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000032:analysis*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D020148:Butyric Acid