Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers

BMC Biotechnology

Suradej Hongeng⁴  Somchai Limsrichamrern²  Pravit Akarasereenont³  Suparerk Borwornpinyo⁵  Lalana Nuntakarn¹  Sunisa Duangsa-ard³  Kanda Kasetsinsombat³  Adisak Wongkajornsilp³  Khanit Sa-ngiamsuntorn³ 

[1]Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchatewi, Bangkok 10400, Thailand

[2]Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand

[3]Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand

[4]Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchatewi, Bangkok 10400, Thailand

[5]Department of Biotechnology, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchatewi, Bangkok 10400, Thailand

关键词: MSC;    CYP450;    immortalization;    hepatocyte-like cell;   

Others  :  1145820
DOI  :  10.1186/1472-6750-11-89

 received in 2011-04-13, accepted in 2011-09-30,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Sa-ngiamsuntorn et al; licensee BioMed Central Ltd.

【 图 表 】

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