Differentiation potential of an immortalized non-tumorigenic human liver epithelial cell line as liver progenitor cells.
We report the differentiation potential of an immortalized non-tumorigenic human liver epithelial cell line, THLE-5b. Under basic culture conditions THLE-5b showed undifferentiated phenotypes. When grown as cell aggregates, THLE-5b exhibited a hepatocyte-like ultrastructure, ammonia metabolic activity and several other indicators that suggest hepatocytic maturation, including up-regulation or induction of liver-specific genes such as albumin and tryptophane 2,3-dioxygenase, and down-regulation of biliary cell markers such as gamma-glutamyl transpeptidase (GGT). Under these conditions, transcriptional factors such as HNF-1 and HNF-4alpha were also up-regulated or induced. In Matrigel culture, expression of GGT was up-regulated. THLE-5b expressed both albumin and alpha 1-antitrypsin, but lost expression of CK19 in severe combined immunodeficient mice. Thus, THLE-5b can be aligned with progenitor cells, which are committed to the hepatocytic or biliary epithelial cell lineage. These results imply that bipotent progenitor cell populations similar to THLE-5b cells may exist in adult human liver.
Tokiwa
T
T
Department of Liver Cell Biology, Kohno Clinical Medicine Research Institute, 3-4-4 Kitashinagawa, Shinagawa, 140-0001 Tokyo, Japan. t.tokiwa@kcmi.or.jp
Yamazaki
T
T
Xin
W
W
Sugae
N
N
Noguchi
M
M
Enosawa
S
S
Tsukiyama
T
T
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology* / Q000637:transplantation / Q000648:ultrastructure; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure
D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human