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Title: Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
Authors: Khanit Sa-ngiamsuntorn
Adisak Wongkajornsilp
Kanda Kasetsinsombat
Sunisa Duangsa-ard
Lalana Nuntakarn
Suparerk Borwornpinyo
Pravit Akarasereenont
Somchai Limsrichamrern
Suradej Hongeng
Mahidol University. Faculty of Medicine Siriraj Hospital. Department of Pharmacology
Keywords: Open Access article;hepatocyte-like cell;immortalization;CYP450;MSC
Issue Date: 2011
Citation: BMC Biotechnology. Vol. 11, (2011), 89
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. Conclusion: 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.
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