Application of human iPS cell-derived intestinal epithelial cells as a novel prediction system for drug disposition and drug interaction

• Project/Area Number: 17K08421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: Iwao Takahiro 名古屋市立大学, 医薬学総合研究院(薬学), 准教授 (50581740)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 小腸 / 薬物動態 / iPS細胞 / ヒトiPS細胞 / 薬学

Outline of Final Research Achievements

We were able to find some useful small molecule compounds in the differentiation of human iPS cells to intestinal epithelial cells in this study. It was indicated that the human iPS cell-derived intestinal epithelial cells had drug metabolizing enzyme activities, CYP3A4 inducibility, drug transporter activities, and barrier functions. In addition, it was suggested that the cells would be available as an evaluation system to predict intestinal drug absorption quantitatively.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトiPS細胞から作製した腸管上皮細胞が医薬品の消化管吸収を定量的に評価できる系としての有用性を示すことができた。現在、よりよい医薬品の消化管吸収予測系の開発が望まれていることから、本研究で得られた成果はこの分野において有用であると考えられる。

Research Products

• [Journal Article] Intestinal cells differentiated from human induced pluripotent stem cells for use in drug development studies (2019)
  • Author(s): Iwao Takahiro、Matsunaga Tamihide
  • Journal Title: Translational and Regulatory Sciences Volume: 1 Issue: 1 Pages: 24-30
  • DOI: 10.33611/trs.1_24
  • NAID: 130007691379
  • ISSN: 2434-4974
  • Peer Reviewed / Open Access
• [Journal Article] Generation of human iPS cell-derived hepatocytes and enterocytes for application to drug disposition studies (2019)
  • Author(s): Iwao Takahiro、Matsunaga Tamihide
  • Journal Title: Folia Pharmacologica Japonica Volume: 154 Issue: 2 Pages: 72-77
  • DOI: 10.1254/fpj.154.72
  • NAID: 130007689400
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] Development of an <i>In Vitro</i> System for Evaluating Intestinal Drug Disposition Using Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Cells (2018)
  • Author(s): Iwao Takahiro
  • Journal Title: YAKUGAKU ZASSHI Volume: 138 Issue: 10 Pages: 1241-1247
  • DOI: 10.1248/yakushi.18-00120
  • NAID: 130007491474
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2018-10-01
  • Peer Reviewed
• [Journal Article] Cyclic AMP signaling promotes the differentiation of human induced pluripotent stem cells into intestinal epithelial cells. (2018)
  • Author(s): Kabeya T, Qiu S, Hibino M, Nagasaki M, Kodama N, Iwao T, and Matsunaga T
  • Journal Title: Drug Metab. Dispos. Volume: 46 Issue: 10 Pages: 1411-1419
  • DOI: 10.1124/dmd.118.082123
  • Peer Reviewed
• [Journal Article] Functional Analysis of Carboxylesterase in Human Induced Pluripotent Stem Cell-derived Enterocytes. (2017)
  • Author(s): Kabeya T, Matsumura W, Iwao T, Hosokawa M, Matsunaga T
  • Journal Title: Biochem Biophys Res Commun Volume: 486 Issue: 1 Pages: 143-148
  • DOI: 10.1016/j.bbrc.2017.03.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 幹細胞からの薬物動態関連臓器細胞の分化誘導技術 (2017)
  • Author(s): 岩尾岳洋，松永民秀
  • Journal Title: 生物工学会誌 Volume: 95 Pages: 461-464
• [Presentation] ヒトiPS細胞由来腸管上皮細胞（F-hiSIEC）の機能解析：薬物吸収予測モデルへの応用とアプリケーション開発 (2019)
  • Author(s): 美馬伸治，今倉悠貴，小椋 泉，後藤 俊，柿沼千早，岩尾岳洋，松永民秀，畠賢一郎
  • Organizer: 日本薬物動態学会第34回年会
• [Presentation] Generation of intestinal cells from human iPS cells for application to drug development study (2019)
  • Author(s): Takahiro Iwao
  • Organizer: NCU Contact Points in Asia Symposium
  • Int'l Joint Research / Invited
• [Presentation] ヒトiPS細胞由来腸管上皮細胞（FUJIFILM human iPS cell-derived Small Intestinal Epithelial like Cell; F-hiSIEC）の特性と腸管吸収評価モデルとしての有用性 (2019)
  • Author(s): 小椋 泉，美馬伸治，今倉悠貴，後藤 俊，柿沼千早，岩尾岳洋，松永民秀，山田忠範，畠賢一郎
  • Organizer: 日本動物実験代替法学会第32回大会
• [Presentation] 医薬品の消化管吸収や毒性評価に利用可能なヒトiPS細胞由来小腸上皮細胞の開発 (2019)
  • Author(s): 岩尾岳洋
  • Organizer: 第4回トランスポーター研究会関東部会
  • Invited
• [Presentation] 創薬研究での利用に向けた小腸-肝臓連結デバイスの開発 (2019)
  • Author(s): 岩尾岳洋
  • Organizer: 第46回日本毒性学会学術大会
  • Invited
• [Presentation] Differentiation of human iPS cells into enterocyte-like cells using cAMP-activating compounds and its function (2019)
  • Author(s): Tamihide Matsunaga, Tomoki Kabeya, Shimeng Qiu, Takahiro Iwao
  • Organizer: International Conference on Cytochrome P450
  • Int'l Joint Research
• [Presentation] ヒトiPS細胞を用いた腸管吸収評価モデルの開発 (2019)
  • Author(s): 今倉悠貴，美馬伸治，小椋 泉，柿沼千早，壁谷知樹，岩尾岳洋，松永民秀，山田忠範，山本 武
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] ヒトiPS細胞由来小腸上皮細胞への分化誘導に対する機能性ポリマーの検討 (2019)
  • Author(s): 邱 施萌，壁谷知樹，岩尾岳洋，松永民秀
  • Organizer: 細胞アッセイ研究会シンポジウム
• [Presentation] ヒトiPS細胞を活用した腸管吸収評価モデルの開発 (2019)
  • Author(s): 美馬伸治，今倉悠貴，小椋 泉，柿沼千早，壁谷知樹，岩尾岳洋，松永民秀，山田忠範，山本 武
  • Organizer: 細胞アッセイ研究会シンポジウム
• [Presentation] cAMP signaling promotes the intestinal differentiation of human induced pluripotent stem cells (2018)
  • Author(s): Tomoki Kabeya, Shimeng Qiu, Momona Hibino, Mizuka Nagasaki, Nao Kodama, Takahiro Iwao, Tamihide Matsunaga
  • Organizer: 2018 International Meeting on 22nd MDO and 33rd JSSX
  • Int'l Joint Research
• [Presentation] Characteristics of human small intestinal epithelial cells derived from induced pluripotent stem cells (2018)
  • Author(s): Shinji Mima, Yuki Imakura, Izumi Ogura, Chihaya Kakinuma, Tomoki Kabeya, Takahiro Iwao, Tamihide Matsunaga, Tadanori Yamada, Takeshi Yamamoto
  • Organizer: 2018 International Meeting on 22nd MDO and 33rd JSSX
  • Int'l Joint Research
• [Presentation] Effects of high-molecule compounds on differentiation to enterocytes derived from human induced pluripotent stem cells (2018)
  • Author(s): Shimeng Qiu, Tomoki Kabeya, Takahiro Iwao, Tamihide Matsunaga
  • Organizer: 2018 International Meeting on 22nd MDO and 33rd JSSX
  • Int'l Joint Research
• [Presentation] ヒトiPS細胞由来腸管上皮細胞モデルにおけるリボフラビントランスポーター機能の検証 (2018)
  • Author(s): 鈴木香帆，太田欣哉，保嶋智也，壁谷知樹，岩尾岳洋，松永民秀，湯浅博昭
  • Organizer: 日本薬学会第138年会
• [Presentation] ヒトiPS細胞由来腸管上皮細胞モデルにおけるclonidine輸送の解析 (2018)
  • Author(s): 難波莉子，保嶋智也，鈴木香帆，壁谷知樹，岩尾岳洋，松永民秀，湯浅博昭
  • Organizer: 日本薬学会第138年会
• [Presentation] ヒトiPS細胞由来組織細胞の作製と薬物動態試験への応用に関する研究 (2017)
  • Author(s): 岩尾岳洋
  • Organizer: 日本薬物動態学会第32回年会
  • Invited
• [Presentation] ヒトiPS細胞由来腸管上皮細胞モデルにおけるPCFT及びASBTの機能の比較検討 (2017)
  • Author(s): 鈴木香帆，太田欣哉，保嶋智也，壁谷知樹，岩尾岳洋，松永民秀，湯浅博昭
  • Organizer: 日本薬物動態学会第32回年会
• [Presentation] 機能性ポリマーはヒトiPS細胞から腸管上皮細胞への分化を促進する (2017)
  • Author(s): 邱 施萌，壁谷知樹，岩尾岳洋，松永民秀
  • Organizer: 日本薬物動態学会第32回年会
• [Presentation] ヒトiPS細胞由来腸管上皮細胞を用いたカルボキシルエステラーゼによる医薬品代謝の予測評価系の開発 (2017)
  • Author(s): 壁谷知樹，松村若菜，岩尾岳洋，細川正清，松永民秀
  • Organizer: 第24回HAB研究機構学術年会
• [Book] 臓器チップの技術と開発動向 (2018)
  • Author(s): 岩尾岳洋，松永民秀
  • Total Pages: 293
  • Publisher: シーエムシー出版
• [Patent(Industrial Property Rights)] 多能性幹細胞の腸管上皮細胞への分化誘導 (2018)
  • Inventor(s): 松永民秀，岩尾岳洋，邱 施萌，金木達朗
  • Industrial Property Rights Holder: 公立大学法人 名古屋市立大学、日産化学工業株式会社
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-210951
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 多能性幹細胞から腸管上皮細胞への分化誘導方法 (2018)
  • Inventor(s): 松永民秀，岩尾岳洋，壁谷知樹，美馬伸治，宮下敏秀
  • Industrial Property Rights Holder: 公立大学法人 名古屋市立大学、富士フイルム株式会社
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-021545
  • Filing Date: 2018