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Expansion of human iPS cell-derived ureteric bud organoids

Research Project

Project/Area Number 19K08703
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionKyoto University

Principal Investigator

Mae Shin-Ichi  京都大学, iPS細胞研究所, 特定拠点助教 (50749801)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsiPS細胞 / 尿管芽 / 腎臓 / 拡大培養 / ヒトiPS細胞 / オルガノイド
Outline of Research at the Start

現在までのところ、ヒトiPS細胞から尿管芽への分化誘導方法は、申請者らを含めて2グル
ープから報告されているが(Taguchi A., 2017; Mae S., 2018)、いずれも生体内の尿管芽で認められるような分枝形態形成がほとんど起こらない。そこで申請者は、尿管芽では常に内腔が存在しながら分枝が起こることに着目し、ヒトiPS細胞から内腔を有する尿管芽オルガノイドを作製する方法を確立し、分枝が起こらない問題点の解決に至っている。本研究では、その成果を発展させ、尿管芽オルガノイドの形成過程における詳細な分子メカニズムと尿管芽の幹細胞である先端細胞の特性の解明を行う。

Outline of Final Research Achievements

We previously established the induction method for branching ureteric bud, one of the renal progenitors, from human induced pluripotent stem cells. In the current study, we have developed a novel expansion culture method for ureteric bud tip cells while maintaining the reconstitution ability of ureteric bud organoids. Moreover, we have clarified that NFkB pathway is crucial for the proliferation of ureteric bud tip cells and found that the long-term expansion culture advances the renal developmental stage to the late branching phase.

Academic Significance and Societal Importance of the Research Achievements

これまでのところ、尿管芽の分枝形態形成における組織幹細胞である尿管芽tip細胞を選択的に拡大培養し、大量の尿管芽オルガノイドを作製する方法は確立されていない。したがって、本研究の成果は新規性および進歩性に優れている。さらに、拡大培養によって発生分化段階が進んだ腎組織を作製可能になることで、腎臓発生機序の解明が進展し、iPS細胞を用いた先天性腎尿路異常の病態解明に貢献することが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

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

  • [Journal Article] Expansion of Human iPSC-Derived Ureteric Bud Organoids with Repeated Branching Potential2020

    • Author(s)
      Mae Shin-Ichi、Ryosaka Makoto、Sakamoto Satoko、Matsuse Kyoko、Nozaki Aya、Igami Maiko、Kabai Ryotaro、Watanabe Akira、Osafune Kenji
    • Journal Title

      Cell Reports

      Volume: 32 Issue: 4 Pages: 107963-107963

    • DOI

      10.1016/j.celrep.2020.107963

    • NAID

      120006876566

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential.2021

    • Author(s)
      Shin-Ichi Mae, Makoto Ryosaka, Kenji Osafune
    • Organizer
      ISSCR 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞を用いた分枝形態形成を行う集合管系譜オルガノイドの作製と再生2021

    • Author(s)
      前伸一、兩坂誠、長船健二
    • Organizer
      第11回分子腎臓フォーラム
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 尿管芽先端部細胞の単離方法2020

    • Inventor(s)
      長船健二、前伸一、兩坂誠
    • Industrial Property Rights Holder
      長船健二、前伸一、兩坂誠
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas

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

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