Differentiation of human iPS cells into hepatocytes and enterocytes: Development of first pass effect assessment model
| Project/Area Number |
26293036
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大森 栄 信州大学, 医学部附属病院, 教授 (70169069)
永田 清 東北医科薬科大学, 薬学部, 教授 (80189133)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | ヒトiPS細胞 / 分化誘導 / 肝細胞 / 腸管上皮細胞 / 初回通過効果 / 薬物代謝酵素 / 薬物トランスポーター / 薬物動態 / 経口バイオアベイラビリティ / デバイス / 薬学 / iPS細胞 / 分化 / 薬物動態学 / 人工多能性幹細胞 / 薬物代謝 / トランスポーター / 低分子化合物 / スクラーゼ・イソマルターゼ |
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| Outline of Final Research Achievements |
Human induced pluripotent stem (iPS) cells are expected to be applicable not only in regenerative medicine but also in drug development such as pharmacokinetic and toxicokinetic studies. In this study, the differentiation in 3D sphere culture was increased the gene expressions or the activity of drug metabolizing enzymes and improved the function of human iPS cell-derived hepatocytes. The small-molecule compounds, PD98059, 5-aza-2-deoxycytidine and A-83-01, were effective in generating pharmacokinetically functional enterocytes from human iPS cells. MEK, DNMT, and TGF-β inhibitors can be used to promote the differentiation of human iPS cells into pharmacokinetically functional enterocytes.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Histone deacetylase inhibitor valproic acid promotes the differentiation of human induced pluripotent stem cells into hepatocyte-like cells.2014
Author(s)
Kondo Y, Iwao T, Yoshihashi S, Mimori K, Ogihara R, Nagata K, Kurose K, Saito M, Niwa T, Suzuki T, Miyata N, Ohmori S, Nakamura K, Matsunaga T.
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Journal Title
PLoS One.
Volume: 9
Issue: 8
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Selective culture method for hepatocyte-like cells differentiated from human induced pluripotent stem cells.2014
Author(s)
Kondo Y, Yoshihashi S, Mimori K, Ogihara R, Kanehama Y, Maki Y, Enosawa S, Kurose K, Iwao T, Nakamura K, Matsunaga T
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Journal Title
Drug Metab Pharmacokinet
Volume: 29
Pages: 407-413
Related Report
Peer Reviewed / Open Access
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[Journal Article] An efficient method for differentiation of human induced pluripotent stem cells into hepatocyte-like cells retaining drug metabolizing activity.2014
Author(s)
Kondo Y, Iwao T, Nakamura K, Sasaki T, Takahashi S, Kamada N, Matsubara T, Gonzalez FJ, Akutsu H, Miyagawa Y, Okita H, Kiyokawa N, Toyoda M, Umezawa A, Nagata K, Matsunaga T, Ohmori S
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Journal Title
Drug Metab Pharmacokinet
Volume: 29
Pages: 237-243
NAID
Related Report
Peer Reviewed / Open Access
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