title: Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers.
abstract: BACKGROUND
  The strenuous procurement of cultured human hepatocytes and their short lives have constrained the cell culture model of cytochrome P450 (CYP450) induction, xenobiotic biotransformation, and hepatotoxicity. The development of continuous non-tumorous cell line steadily containing hepatocyte phenotypes would substitute the primary hepatocytes for these studies.
  
  
  RESULTS
  The hepatocyte-like cells have been developed from hTERT plus Bmi-1-immortalized human mesenchymal stem cells to substitute the primary hepatocytes. The hepatocyte-like cells had polygonal morphology and steadily produced albumin, glycogen, urea and UGT1A1 beyond 6 months while maintaining proliferative capacity. Although these hepatocyte-like cells had low basal expression of CYP450 isotypes, their expressions could be extensively up regulated to 80 folds upon the exposure to enzyme inducers. Their inducibility outperformed the classical HepG2 cells.
  
  
  CONCLUSIONS
  The hepatocyte-like cells contained the markers of hepatocytes including CYP450 isotypes. The high inducibility of CYP450 transcripts could serve as a sensitive model for profiling xenobiotic-induced expression of CYP450.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand.
authors.forename: Khanit
authors.initials: K
authors.lastname: Sa-ngiamsuntorn
authors.forename: Adisak
authors.initials: A
authors.lastname: Wongkajornsilp
authors.forename: Kanda
authors.initials: K
authors.lastname: Kasetsinsombat
authors.forename: Sunisa
authors.initials: S
authors.lastname: Duangsa-ard
authors.forename: Lalana
authors.initials: L
authors.lastname: Nuntakarn
authors.forename: Suparerk
authors.initials: S
authors.lastname: Borwornpinyo
authors.forename: Pravit
authors.initials: P
authors.lastname: Akarasereenont
authors.forename: Somchai
authors.initials: S
authors.lastname: Limsrichamrern
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000032:analysis; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*; D015854:Up-Regulation; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology*; D000099148:UGT1A1 Enzyme
chemical_list: D015415:Biomarkers; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D015262:Xenobiotics; D000099148:UGT1A1 Enzyme