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Pathological analysis and drug discovery for stomach cancer using human stomach organoids

Research Project

Project/Area Number 17H00861
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Kurisaki AKIRA  奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (60346616)

Co-Investigator(Kenkyū-buntansha) 原本 悦和  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (30540869)
畠山 昌則  東京大学, 大学院医学系研究科(医学部), 教授 (40189551)
高田 仁実  奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (80641068)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2019: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2018: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2017: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Keywords胃 / 分化 / 幹細胞 / 遺伝子 / ES細胞 / iPS細胞 / がん / オルガノイド
Outline of Final Research Achievements

The purpose of this study was to create an in vitro disease model of the stomach infected with H. pylori using stomach organoid. We had developed a culture method to produce functional mini-stomach tissue organoids and the precancerous state model of the organoids from mouse ES cells. In this research, we took advantage of this system to establish several knock-in ES cell lines capable of inducing the major pathogenic gene of H. pylori. However, these ES cells gradually decreased the induction of exogenous genes with unknown reasons. For the differentiation of mini-stomach tissue using human iPS cells, the medium and culture conditions for embryoid body formation, foregut endoderm induction, and gastric progenitor cell differentiation were optimized.

Academic Significance and Societal Importance of the Research Achievements

本研究では既に作製方法を確立済みのマウス胃オルガノイドを利用して、病原タンパク質を発現するES細胞を樹立したが、徐々に発現量が低下する問題があり、原因究明中である。また、ヒトiPS細胞を用いた胃オルガノイドの作製に関しては、胃の前駆細胞を作製する分化培養条件を最適化することができた。今後この研究を進めることで、将来的にはピロリ菌病原タンパク質を発現させたミニ胃組織(胃オルガノイド)を幹細胞からシャーレの中で作製し、ピロリ菌に感染した胃の細胞で起こる現象を詳細に解析することや新たな治療薬の探索が可能になると期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (10 results)

All 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (2 results)

  • [Journal Article] 胃オルガノイド作製と病態モデル2019

    • Author(s)
      栗崎晃、高田仁実
    • Journal Title

      Medical Science Direct

      Volume: 45 Pages: 14-17

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors2018

    • Author(s)
      K. Miyazono, S. Moriwaki, T. Ito, A. Kurisaki, M. Asashima, M. Tanokura.
    • Journal Title

      Sci. Signal.

      Volume: 11 Issue: 523

    • DOI

      10.1126/scisignal.aao7227

    • URL

      https://pure.teikyo.jp/en/publications/2e077a44-cb2b-4816-afa4-eadc9959364c

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis for receptor-regulated SMAD recognition by MAN12018

    • Author(s)
      Miyazono Ken-ichi、Ohno Yosuke、Wada Hikaru、Ito Tomoko、Fukatsu Yui、Kurisaki Akira、Asashima Makoto、Tanokura Masaru
    • Journal Title

      Nucleic Acids Research

      Volume: 46 Issue: 22 Pages: 12139

    • DOI

      10.1093/nar/gky925

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quartz-Seq2: a high-throughput single-cell RNA-sequencing method that effectively uses limited sequence reads2018

    • Author(s)
      Sasagawa Yohei、Danno Hiroki、Takada Hitomi、Ebisawa Masashi、Tanaka Kaori、Hayashi Tetsutaro、Kurisaki Akira、Nikaido Itoshi
    • Journal Title

      Genome Biology

      Volume: 19 Issue: 1 Pages: 1-24

    • DOI

      10.1186/s13059-018-1407-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 成熟胃オルガノイドの分化培養条件検討2019

    • Author(s)
      黒岩隆史、高田仁実、栗崎晃
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Differentiation of pluripotent stem cells and the regulatory mechanisms2019

    • Author(s)
      Akira Kurisaki
    • Organizer
      3rd International Conference on Molecular Biology and Biotechnology 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Differentiation of pluripotent stem cells and the regulatory mechanisms2019

    • Author(s)
      Akira Kurisaki
    • Organizer
      3rd International Conference for Molecular Biology and Biotechnology (ICMBB) 2019
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] THE GLOBAL PICTURE OF CELL-TYPE COMPOSITION IN THE STROMAL VASCULAR FRACTION PREPARED FROM MOUSE ADIPOSE TISSUE2018

    • Author(s)
      Hitomi Takada, Yohei Sasagawa, Hiroki Danno, Masashi Ebisawa, Kaori Tanaka,Tetsutaro Hayashi, Itoshi Nikaido, Akira Kurisaki
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] 決定版 オルガノイド実験スタンダード2019

    • Author(s)
      佐藤 俊朗、武部 貴則、永樂 元次
    • Total Pages
      372
    • Publisher
      羊土社
    • ISBN
      9784758122399
    • Related Report
      2019 Annual Research Report
  • [Book] オルガノイド実験スタンダード (12章 胃オルガノイド)2019

    • Author(s)
      栗崎晃、高田仁実(分担執筆)
    • Total Pages
      368
    • Publisher
      羊土社
    • ISBN
      9784758122399
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2023-01-30  

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