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Establishment of disease models and elucidation of the pathogenesis of inflammatory bowel disease using human iPS cells

Research Project

Project/Area Number 19K08453
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

kakimoto kazuki  大阪医科薬科大学, 医学部, 講師 (20589816)

Co-Investigator(Kenkyū-buntansha) 友田 紀一郎  大阪医科薬科大学, 医学部, 非常勤講師 (50362843)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords炎症性腸疾患 / iPS細胞 / オートファジー / iPS / 腸管上皮細胞 / 腸上皮細胞
Outline of Research at the Start

誘導性多能性幹細胞(induced pluripotent stem cells: iPS細胞)は、再生医療のみならず、疾患の病態解明や創薬研究の基盤技術として期待されている。本研究では、未だ根本的治療法のない原因不明の難病である炎症性腸疾患(Inflammatory Bowel Disease: IBD)における新たな研究基盤となるべく、ヒトiPS細胞を用いてIBD疾患モデリングを確立する。具体的には、健常人およびIBD患者由来iPS細胞から腸管組織へ分化誘導し、in vitroでの腸管炎症モデルを作製した上で、病態解明や新規治療標的の探索を行う。

Outline of Final Research Achievements

Induced pluripotent stem cells (iPS cells) are expected to be a fundamental technology not only for regenerative medicine but also for elucidating the pathophysiology of diseases and drug discovery research. In this study, we attempted to generate a disease model of inflammatory bowel disease using human iPS cells to provide a new research platform for inflammatory bowel disease, for which there is still no fundamental cure. We induced differentiation of intestinal epithelial cells from healthy human iPS cells into intestinal epithelial cells in the small intestine and generated an intestinal inflammatory model in vitro. We also suppressed ATG16L1, a susceptibility gene for inflammatory bowel disease, and elucidated part of the pathological mechanism by which autophagy is involved in intestinal inflammation.

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患の研究手法としては一般的に、マウス等による動物実験や、ヒトの腸管組織検体を用いた研究などが行われているが、動物実験では種間の差異が存在し、ヒト組織においては検体採取に限界がある。ヒトiPS細胞から腸管組織へと分化させ、炎症性腸疾患の疾患モデルとして研究に用いることが可能となれば、種間の差異や検体採取の限界といった従来の課題が解決され、今後、創薬研究や病態メカニズムの解明に繋がることが期待される。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2021 2020

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Examination of autophagy using human induced pluripotent stem cells derived epithelium-like cells2021

    • Author(s)
      Kazuki Kakimoto, Yoshihiro Tatsumi, Yuka Kawasaki, Yasuyoshi Tanaka, Hideki Tawa, Ryouji Koshiba, Yutaka Naka, Yuki Hirata, Takako Miyazaki, Toshihisa Takeuchi, Shiro Nakamura, Kazuhide Higuchi
    • Organizer
      Digestive Disease Week 2021 (国際学会)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞由来の腸管上皮様細胞を用いた炎症性腸疾患関連遺伝子ATG16L1の検討2020

    • Author(s)
      柿本一城
    • Organizer
      第28回日本消化器関連学会週間(第62回 日本消化器病学会大会)
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒトiPS細胞由来の腸管上皮様細胞を用いた炎症性腸疾患関連遺伝子ATG16L1の検討2020

    • Author(s)
      柿本一城、辻本裕之、樋口和秀
    • Organizer
      日本消化器病学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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