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

<p>Abstract</p> <p>Background</p> <p>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 continu...

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Main Authors: Limsrichamrern Somchai, Akarasereenont Pravit, Borwornpinyo Suparerk, Nuntakarn Lalana, Duangsa-ard Sunisa, Kasetsinsombat Kanda, Wongkajornsilp Adisak, Sa-ngiamsuntorn Khanit, Hongeng Suradej
Format: Article
Language:English
Published: BMC 2011-09-01
Series:BMC Biotechnology
Subjects:
Online Access:http://www.biomedcentral.com/1472-6750/11/89
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author Limsrichamrern Somchai
Akarasereenont Pravit
Borwornpinyo Suparerk
Nuntakarn Lalana
Duangsa-ard Sunisa
Kasetsinsombat Kanda
Wongkajornsilp Adisak
Sa-ngiamsuntorn Khanit
Hongeng Suradej
author_facet Limsrichamrern Somchai
Akarasereenont Pravit
Borwornpinyo Suparerk
Nuntakarn Lalana
Duangsa-ard Sunisa
Kasetsinsombat Kanda
Wongkajornsilp Adisak
Sa-ngiamsuntorn Khanit
Hongeng Suradej
author_sort Limsrichamrern Somchai
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-8b9c6c070b7344f1864b2bf8a375f81e2022-12-21T19:11:14ZengBMCBMC Biotechnology1472-67502011-09-011118910.1186/1472-6750-11-89Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducersLimsrichamrern SomchaiAkarasereenont PravitBorwornpinyo SuparerkNuntakarn LalanaDuangsa-ard SunisaKasetsinsombat KandaWongkajornsilp AdisakSa-ngiamsuntorn KhanitHongeng Suradej<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1472-6750/11/89hepatocyte-like cellimmortalizationCYP450MSC
spellingShingle Limsrichamrern Somchai
Akarasereenont Pravit
Borwornpinyo Suparerk
Nuntakarn Lalana
Duangsa-ard Sunisa
Kasetsinsombat Kanda
Wongkajornsilp Adisak
Sa-ngiamsuntorn Khanit
Hongeng Suradej
Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
BMC Biotechnology
hepatocyte-like cell
immortalization
CYP450
MSC
title Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
title_full Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
title_fullStr Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
title_full_unstemmed Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
title_short Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived from mesenchymal stem cells by enzyme inducers
title_sort upregulation of cyp 450s expression of immortalized hepatocyte like cells derived from mesenchymal stem cells by enzyme inducers
topic hepatocyte-like cell
immortalization
CYP450
MSC
url http://www.biomedcentral.com/1472-6750/11/89
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