An Efficient Method for Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-like Cells Retaining Drug Metabolizing Activity
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- KONDO Yuki
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- IWAO Takahiro
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- NAKAMURA Katsunori
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- SASAKI Takamitsu
- Department of Environmental Health Science, Tohoku Pharmaceutical University
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- TAKAHASHI Shogo
- Department of Environmental Health Science, Tohoku Pharmaceutical University
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- KAMADA Noboru
- Kissei Pharmaceutical Co. Ltd.
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- MATSUBARA Tsutomu
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka City University
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- GONZALEZ Frank J.
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health
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- AKUTSU Hidenori
- Department of Reproductive Biology, National Institute for Child Health and Development
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- MIYAGAWA Yoshitaka
- Department of Developmental Biology, National Institute for Child Health and Development
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- OKITA Hajime
- Department of Developmental Biology, National Institute for Child Health and Development
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- KIYOKAWA Nobutaka
- Department of Developmental Biology, National Institute for Child Health and Development
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- TOYODA Masashi
- Department of Reproductive Biology, National Institute for Child Health and Development
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- UMEZAWA Akihiro
- Department of Reproductive Biology, National Institute for Child Health and Development
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- NAGATA Kiyoshi
- Department of Environmental Health Science, Tohoku Pharmaceutical University
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- MATSUNAGA Tamihide
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- OHMORI Shigeru
- Division of Pharmacy, Shinshu University Hospital
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抄録
The use of human induced pluripotent stem (iPS) cells would be of great value for a variety of applications involving drug development studies. Several reports have been published on the differentiation of human iPS cells into hepatocyte-like cells; however, the cells were insufficient for application in drug metabolism studies. In this study, we aimed to establish effective methods for differentiation of human iPS cells into hepatocytes. Two human iPS cell lines were differentiated by addition of activin A, dimethyl sulfoxide, hepatocyte growth factor, oncostatin M, and dexamethasone. The differentiated cells expressed hepatocyte markers and drug-metabolizing enzymes, revealing that the human iPS cells were differentiated into hepatocyte-like cells. Expression of CYP3A4 and UGT1A1 mRNAs increased with treatment with typical inducers of the enzymes, and the response of the cells against the inducers was similar to that of human hepatocytes. Furthermore, the drug-metabolizing activity of CYP3A4, as monitored by testosterone 6β-hydroxylase activity, was elevated by these inducers. In conclusion, we established methods for differentiation of hepatocyte-like cells expressing drug metabolizing activity from human iPS cells. The hepatocyte-like cells derived from human iPS cells will be useful for drug metabolism studies.
収録刊行物
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- Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ
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Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 29 (3), 237-243, 2014
日本薬物動態学会