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Isolation of human iPS-cell derived intestinal stem cells and constitution of pharmacokinetic evaluation system

Research Project

Project/Area Number 15K18929
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionNagoya City University

Principal Investigator

Iwao Takahiro  名古屋市立大学, 大学院薬学研究科, 准教授 (50581740)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsiPS細胞 / 小腸 / 幹細胞 / 薬物動態 / ヒトiPS細胞 / 消化管
Outline of Final Research Achievements

This study indicated to be possible to isolate and maintain human iPS cell-derived intestinal cells. The isolated cells were intestinal stem cell-like cells and had a capacity of differentiation to the enterocytes. The maintained cells remained having a stemness after a certain period of a maintenance culture. When the maintained cells were differentiated to the enterocytes, the cells had pharmocokinetic functions such as CYP3A4 activity, CYP3A4 inducibility, and transporter activities of efflux transporters. It was thought that these results could be useful technical information to use of human iPS cell-derived enterocytes in drug development studies.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characteristic analysis of intestinal absorption in enterocyte-like cells differentiated from human induced pluripotent stem cells.2016

    • Author(s)
      Kodama N, Iwao T, Ohta K, Yuasa H, Matsunaga T
    • Journal Title

      Drug Metab. Dispos.

      Volume: 44 Issue: 10 Pages: 1662-1667

    • DOI

      10.1124/dmd.116.069336

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヒトiPS細胞の分化誘導の現状と創薬研究への応用2016

    • Author(s)
      岩尾岳洋,松永民秀
    • Journal Title

      HAB Newsletter

      Volume: 22 Pages: 6-7

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes2016

    • Author(s)
      Kodama N, Iwao T, Kabeya T, Horikawa T, Niwa T, Kondo Y, Nakamura K, Matsunaga T
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: in press Issue: 3 Pages: 193-200

    • DOI

      10.1016/j.dmpk.2016.02.002

    • NAID

      50014431261

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of a human intestinal epithelial cell monolayer to the prediction of oral drug absorption in humans as a superior alternative to the Caco-2 cell monolayer2016

    • Author(s)
      Takenaka T, Harada N, Kuze J, Chiba M, Iwao T, Matsunaga T
    • Journal Title

      J Pharm Sci

      Volume: 105 Issue: 2 Pages: 915-924

    • DOI

      10.1016/j.xphs.2015.11.035

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of enterocyte-like cells with pharmacokinetic functions from human induced pluripotent stem cells using small-molecule compounds2015

    • Author(s)
      Iwao T, Kodama N, Kondo Y, Kabeya T, Nakamura K, Horikawa T, Niwa T, Kurose K, Matsunaga T
    • Journal Title

      Drug Metab Dispos

      Volume: 43 Issue: 4 Pages: 603-610

    • DOI

      10.1124/dmd.114.062604

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 個別化(オーダーメイド)医療を志向した薬物動態研究および毒性試験へのヒトiPS細胞の利用2015

    • Author(s)
      岩尾岳洋,松永民秀
    • Journal Title

      Organ Biology

      Volume: 22 Pages: 39-48

    • NAID

      130005098698

    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトiPS細胞由来腸管上皮細胞におけるカルボキシルエステラーゼの機能解析2017

    • Author(s)
      壁谷知樹,松村若菜,岩尾岳洋,細川正清,松永民秀
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 基底膜成分を用いたヒトiPS細胞由来小腸幹細胞の単離2017

    • Author(s)
      邱 施萌,長崎瑞佳,壁谷知樹,岩尾岳洋,松永民秀
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] カニクイザルiPS細胞由来腸管オルガノイドの長期培養2017

    • Author(s)
      木田有里子,小野里太智,赤川 巧,小枝暁子,岩尾岳洋,松永民秀
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] カニクイザルiPS細胞由来腸管オルガノイドを用いた薬物動態学的機能解析2017

    • Author(s)
      小野里太智,山下美紗季,木田有里子,小枝暁子,岩尾岳洋,松永民秀
    • Organizer
      細胞アッセイ研究会シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトiPS細胞由来腸管オルガノイドの機能評価2017

    • Author(s)
      山下美紗季,小野里太智,赤川 巧,岩尾岳洋,松永民秀
    • Organizer
      細胞アッセイ研究会シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトiPS細胞由来腸管上皮細胞の薬物動態学的機能特性2016

    • Author(s)
      岩尾岳洋
    • Organizer
      日本薬物動態学会第31回年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 機能的なカニクイザルiPS細胞由来腸管オルガノイドの作製2016

    • Author(s)
      小野里太智,赤川 巧,山下美紗季,木田有里子,小枝暁子,岩尾岳洋,松永民秀
    • Organizer
      日本薬物動態学会第31回年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトiPS細胞からの腸管オルガノイドの作製2016

    • Author(s)
      山下美紗季,小野里太智,赤川 巧,岩尾岳洋,松永民秀
    • Organizer
      日本薬物動態学会第31回年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Small molecule compounds enhance the differentiation of human induced pluripotent stem cells to enterocytes with pharmacokinetic functions2016

    • Author(s)
      Tomoki Kabeya, Takahiro Iwao, Nao Kodama, Tamihide Matsunaga
    • Organizer
      11th International ISSX Meeting
    • Place of Presentation
      Busan, Korea
    • Year and Date
      2016-06-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Small molecule compounds enhance the differentiation of human induced pluripotent stem cells to enterocytes with pharmacokinetic functions2016

    • Author(s)
      Kabeya T, Iwao T, Kodama N, Matsunaga T
    • Organizer
      11th International ISSX Meeting
    • Place of Presentation
      釜山(韓国)
    • Year and Date
      2016-06-12
    • Related Report
      2015 Research-status Report
    • 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小腸特異的葉酸トランスポーター機能の検証2016

    • Author(s)
      鈴木香帆,片野貴大,太田欣哉,保嶋智也,壁谷知樹,小玉菜央,岩尾岳洋,松永民秀
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      岐阜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Presentation] ヒトiPS細胞由来腸管上皮細胞への分化と薬物動態機能評価2016

    • Author(s)
      岩尾岳洋
    • Organizer
      日本薬物動態学会第10回ショートコース
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Invited
  • [Presentation] ヒト人工多能性幹細胞の腸管への分化に対する低分子化合物の有用性2015

    • Author(s)
      壁谷知樹,岩尾岳洋,小玉菜央,中村克徳,松永民秀
    • Organizer
      日本薬物動態学会第30回年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト人工多能性幹細胞から分化誘導した腸管上皮細胞様細胞の薬物動態学的特性解析2015

    • Author(s)
      小玉菜央,岩尾岳洋,壁谷知樹,中村克徳,松永民秀
    • Organizer
      日本薬物動態学会第30回年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト人工多能性幹細胞由来腸管上皮細胞の薬物動態学的機能評価2015

    • Author(s)
      岩尾岳洋,小玉菜央,壁谷知樹,松永民秀
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2015
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 低分子化合物によるヒトiPS細胞から機能的な腸管上皮細胞への分化促進2015

    • Author(s)
      小玉菜央,岩尾岳洋,松永民秀
    • Organizer
      第22回HAB研究機構学術年会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトiPS細胞の腸管上皮細胞への分化と薬物動態機能評価2015

    • Author(s)
      岩尾岳洋
    • Organizer
      第22回HAB研究機構学術年会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 人工多能性幹細胞の腸管上皮細胞への分化誘導2017

    • Inventor(s)
      岩尾岳洋,壁谷知樹,松永民秀
    • Industrial Property Rights Holder
      岩尾岳洋,壁谷知樹,松永民秀
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-03-03
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 人工多能性幹細胞由来腸管幹細胞の維持培養2017

    • Inventor(s)
      岩尾岳洋,松永民秀,近藤聡志
    • Industrial Property Rights Holder
      岩尾岳洋,松永民秀,近藤聡志
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-029448
    • Filing Date
      2017-02-20
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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