Evaluation of Human Embryonic Stem Cell-derived Hepatocyte-like Cells for Detection of CYP1A Inducers
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- TSUCHIYA Hiroyuki
- Department of Pharmacy, Shinshu University Hospital
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- MATSUNAGA Tamihide
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- AIKAWA Kaori
- Department of Pharmacy, Shinshu University Hospital
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- KAMADA Noboru
- Basic Discovery Research, R&D Kissei Pharmaceutical Co., Ltd.
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- NAKAMURA Katsunori
- Department of Pharmacy, Shinshu University Hospital
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- ICHIKAWA Hinako
- Department of Histology and Embryology, Medical School of Shinshu University
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- SASAKI Katsunori
- Department of Histology and Embryology, Medical School of Shinshu University
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- OHMORI Shigeru
- Department of Pharmacy, Shinshu University Hospital
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Abstract
There is a great deal of interest in differentiation of human embryonic stem cells (hESCs) into hepatocyte-like cells for application in pharmaceutical screening. Cytochrome P450 (CYP) 1A is involved in the metabolic activation of procarcinogenic compounds as well as in detoxification of drugs. We differentiated hESCs into hepatocyte-like cells (hESC-derived hepatocyte-like cells) and examined whether CYP1A was induced in these cells by typical inducers of CYP1A. hESC-derived hepatocyte-like cells expressed albumin, α-fetoprotein, CYP3A4, CYP3A7, CYP1A1, CYP1A2, and UDP-glucuronyl transferase (UGT) 1A1 mRNA. The levels of CYP1A1, CYP1A2, and UGT1A1 mRNA expression were increased by omeprazole and 3-methylcholanthrene. Furthermore, the enzyme activity of CYP1A was also increased by these compounds. In conclusion, hESC-derived hepatocyte-like cells are available for the detection of CYP1A inducers.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 27 (6), 598-604, 2012
The Japanese Society for the Study of Xenobiotics