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Establishment of differentiation induction method from iPS cells to mature oligodendrocytes and application to myelin sheath regeneration therapy

Research Project

Project/Area Number 17K07120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Defense Medical College

Principal Investigator

IMAMURA OSAMU  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 生化学, 准教授 (40534954)

Co-Investigator(Kenkyū-buntansha) 瀧嶋 邦夫  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 生化学, 教授 (50531365)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脱髄疾患 / ドネペジル / エストロゲン受容体 / iPS細胞 / オリゴデンドロサイト / 神経幹細胞 / 髄鞘形成
Outline of Final Research Achievements

In this study, we elucidated the mechanism of action of donepezil (DNP) induction of oligodendrocyte differentiation using iPS cells, and developed a DNP-based oligodendrocyte differentiation induction method to be used for demyelination therapy. The results of this study revealed that the estrogen receptor (ER)-mediated pathway is important for DNP-induced differentiation of mouse iPS cell-derived neural stem cells into oligodendrocytes. In addition, we confirmed that DNP also induces differentiation of human iPS cells into oligodendrocytes.

Academic Significance and Societal Importance of the Research Achievements

脱髄疾患の治療標的は免疫系であり、疾患の進行抑制と再発予防を狙った対症療法が主体となっている。本研究においてDNPによるオリゴデンドロサイトへの分化促進作用にはERを介する経路が重要であることを明らかにした。ER経路の活性化は、オリゴデンドロサイトへの分化誘導や髄鞘形成を促進させ、脱髄疾患モデル動物の病態を改善することが報告されているため、今後、本研究成果に基づきオリゴデンドロサイト分化誘導活性を標的にした新たな脱髄疾患治療薬の創出が期待される。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2020 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (1 results)

  • [Journal Article] Donepezil-induced Oligodendrocyte Differentiation Is Mediated Through Estrogen Receptors2020

    • Author(s)
      Osamu Imamura , Masaaki Arai , Minori Dateki , Kazuhiko Oishi , Kunio Takishima
    • Journal Title

      J Neurochem

      Volume: 155(5) Issue: 5 Pages: 494-507

    • DOI

      10.1111/jnc.14927

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Donepezil promotes differentiation of neural stem cells into mature oligodendrocytes at the expense of astrogenesis.2017

    • Author(s)
      Imamura O, Arai M, Dateki M, Takishima K.
    • Journal Title

      J Neurochem.

      Volume: 140 Pages: 231-244

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Donepezil promotes differentiation of neural stem cells into mature oligodendrocytes at the expense of astrogenesis2017

    • Author(s)
      Imamura O, Arai M, Dateki M, Takishima K.
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report

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

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