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Construction of a model for intestinal toxicity test using human and monkey iPS cells and search for toxic biomarker

Research Project

Project/Area Number 16K15164
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

Matsunaga Tamihide  名古屋市立大学, 大学院薬学研究科, 教授 (40209581)

Co-Investigator(Renkei-kenkyūsha) IWAO Takahiro  名古屋市立大学, 大学院薬学研究科, 准教授 (50581740)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsヒトiPS細胞 / カニクイザルiPS細胞 / 腸管上皮細胞 / 腸管オルガノイド / 抗がん剤 / 細胞毒性 / 腸管毒性試験 / サルiPS細胞 / 低分子化合物 / 分化誘導 / 毒性試験 / 分化 / 薬学 / iPS細胞 / オルガノイド
Outline of Final Research Achievements

In the differentiation of human iPS cells into enterocytes, the mRNA expression levels of intestinal markers and pharmacokinetic-related factors were increased by addition of small molecule compounds. On the other hand, these mRNA expression levels were increased by high molecule compounds. These results suggested that these compounds contribute obtain of intestinal functions.
Intestinal organoids were useful as a toxicity evaluation system, because dose-dependent cytotoxicity was observed by an anti-cancer drug 5-FU. The mRNA expression of inflammatory cytokines and markers of regenerative intestinal epithelial stem cells was increased by 5-FU. These results suggested that these expression changes are promising as cytotoxic markers.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (29 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Efficient generation of cynomolgus monkey induced pluripotent stem cell-derived intestinal organoids.2018

    • Author(s)
      Onozato D, Yamashita M, Fukuyama R, Akagawa T, Kida Y, Koeda A, Iwao T, Matsunaga T.
    • Journal Title

      Stem Cells and Development

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of intestinal organoids suitable for pharmacokinetic studies from human induced pluripotent stem cells.2018

    • Author(s)
      Onozato D, Yamashita M, Nakanishi A, Akagawa T, Kida Y, Ogawa I, Hashita T, Iwao T, and Matsunaga T
    • Journal Title

      Drug Metab. Dispos.

      Volume: 46 Issue: 11 Pages: 1572-1580

    • DOI

      10.1124/dmd.118.080374

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規浮遊剤を用いたヒトiPS細胞由来腸管オルガノイドの作製.2018

    • Author(s)
      小川 勇,小野里太智,岩尾岳洋,松永民秀
    • Organizer
      細胞アッセイ研究会シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトiPS細胞由来腸管オルガノイドを用いた炎症性腸疾患モデルの構築.2018

    • Author(s)
      小野里太智,赤川 巧,木田有里子,小川 勇,岩尾岳洋,松永民秀
    • Organizer
      細胞アッセイ研究会シンポジウム
    • Related Report
      2017 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
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [Presentation] 薬物動態学的機能を有するヒトiPS細胞由来腸管オルガノイドの作製.2017

    • Author(s)
      小野里太智,山下美紗季,赤川 巧,木田有里子,中西杏奈,岩尾岳洋,松永民秀
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 効率的な3次元培養によるヒトiPS細胞由来腸管オルガノイドの作製.2017

    • Author(s)
      小川 勇,小野里太智,坡下真大,岩尾岳洋,金木達朗,松永民秀
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞由来小腸幹細胞維持培養法の確立.2017

    • Author(s)
      水野翔太,近藤聡志,岩尾岳洋,松永民秀
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトiPS細胞由来腸管オルガノイドを用いた抗がん剤による消化管障害の評価系の構築.2017

    • Author(s)
      赤川 巧,小野里太智,木田有里子,山下美紗季,岩尾岳洋,松永民秀
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Efficient generation of human and cynomolgus monkey induced pluripotent stem cell-derived intestinal organoids with pharmacokinetic functions.2017

    • Author(s)
      Daichi Onozato, Misaki Yamashita, Anna Nakanishi, Takumi Akagawa, Yuriko Kida, Akiko Koeda, Takahiro Iwao, Tamihide Matsunaga
    • Organizer
      21st North American ISSX Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of novel culture method for maintaining stemness of human iPS cell-derived intestinal stem cells.2017

    • Author(s)
      Satoshi Kondo, Shota Mizuno, Yue Yu, Wakana Matsumura, Takahiro Iwao, Tamihide Matsunaga
    • Organizer
      21st North American ISSX Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞由来原始下部消化管幹細胞を用いた培養下発がん研究系の開発.2017

    • Author(s)
      小宮雅美,藤井 元,宮本真吾,中西るり,鱧屋隆博,田村秀哉,黒川友理絵,高橋麻衣子,岩尾岳洋,松永民秀,武藤倫弘
    • Organizer
      第24回日本がん予防学会総会
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 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
      シンポジウム:細胞アッセイ技術の現状と将来
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] マイクロカプセル内でのヒトiPS細胞由来肝細胞の作製.2017

    • Author(s)
      大西 琢,小野里太智,岩尾岳洋,境 慎司,田谷正仁,松永民秀
    • Organizer
      シンポジウム:細胞アッセイ技術の現状と将来
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status 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
      シンポジウム:細胞アッセイ技術の現状と将来
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] Generation of functional cynomolgus monkey iPS cell-derived intestinal organoids.2016

    • Author(s)
      Onozato D, Akagawa T, Yamashita M, Kida Y, Koeda A, Iwao T, Matunaga T
    • 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 Research-status Report
  • [Presentation] Microencapsulation of human induced pluripotent stem cell-derived hepatocytes.2016

    • Author(s)
      Onish T, Onozato D, Iwao T, Sakai S, Taya M, Matsunaga T
    • 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 Research-status 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 Research-status 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,松永民秀
    • Organizer
      日本薬物動態学会第31回年会 日本再生医療学会共催シンポジウム
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 消化管の薬物動態及び毒性試験における新規創薬研究支援材料.2016

    • Author(s)
      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 Research-status Report
    • Invited
  • [Presentation] Small molecule compounds enhance the differentiation of human induced pluripotent stem cells to enterocytes with pharmacokinetic functions.2016

    • 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
      2016 Research-status Report
    • Int'l Joint Research
  • [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)
      松永民秀、岩尾岳洋、近藤聡志
    • Industrial Property Rights Holder
      松永民秀、岩尾岳洋、近藤聡志
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-029448
    • Filing Date
      2017-02-20
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 人工多能性幹細胞から腸管上皮細胞への分化誘導2017

    • Inventor(s)
      松永民秀、岩尾岳洋、壁谷知樹
    • Industrial Property Rights Holder
      松永民秀、岩尾岳洋、壁谷知樹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-03-03
    • Related Report
      2016 Research-status Report
    • Overseas

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Published: 2016-04-21   Modified: 2021-01-27  

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