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Development of a brain environment model and pathological detection system as a basis for iPS cell analysis in Parkinson's disease

Research Project

Project/Area Number 21K07301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionJuntendo University

Principal Investigator

SHIGA Takahiro  順天堂大学, 大学院医学研究科, 特任助教 (50784378)

Co-Investigator(Kenkyū-buntansha) 野中 里紗  順天堂大学, 大学院医学研究科, 特任助教 (90614248)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords老化 / iPS細胞 / 成熟 / 神経変性疾患 / 病態モデル / パーキンソン病
Outline of Research at the Start

我が国の高齢化が進むにつれて、高齢発症神経変性疾患を患う人の割合が増大することが危惧される。神経変性疾患に対するアプローチとしてiPS細胞を用いた神経変性疾患モデルの研究が多く報告されているが、時間軸・脳構造・解析技術を考慮していない研究が多く、患者剖検脳に見られる病態を確認できている例はほとんど存在しない。本研究計画の目的は、申請者が確立している①老化を促進させる低分子化合物、②効率的なグリア系細胞への誘導、③ゲノム編集を用いた最適モデルの構築の3つの技術を応用して、平面上に高齢期の脳構造を模倣した新たなデバイスを作成し、高齢発症神経変性疾患の病態解析に応用することを目指す。

Outline of Final Research Achievements

As our country ages, there is growing concern about the increasing proportion of people suffering from late-onset neurodegenerative diseases. Although many studies have reported on neurodegenerative disease models using iPS cells, most do not consider the time axis, brain structure, or analysis techniques, resulting in few examples that replicate the pathology observed in postmortem brains. This research aimed to apply the applicant's established techniques-using low molecular compounds that promote aging and efficient induction of glial cells-to create a new device that mimics the brain structure of old age on a flat surface, and to use it for the pathological analysis of late-onset neurodegenerative diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究で確立された技術は、多検体の高齢発症神経変性疾患病態解析や創薬スクリーニングに適した手法の開発を目的として構築した基盤システムであり、従来の単層培養法と比較してして高精度な結果を得ることができる。さらに、時間軸・脳内環境を模倣したモデルのため、ヒト剖検脳に近いデータを取得できる可能性を秘めている。また、様々な神経変性疾患にも応用可能なシステムなため、効率的に病態表現型や創薬スクリーニング行うことができる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (1 results)

  • [Journal Article] Involvement of kallikrein‐PAR2‐proinflammatory pathway in severe trastuzumab‐induced cardiotoxicity2022

    • Author(s)
      Sasaki Ritsuko、Kurebayashi Nagomi、Eguchi Hidetaka、Horimoto Yoshiya、Shiga Takahiro、Miyazaki Sakiko、Kashiyama Taku、Akamatsu Wado、Saito Mitsue
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 10 Pages: 3449-3462

    • DOI

      10.1111/cas.15508

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased excitability of human iPSC-derived neurons in HTR2A variant-related sleep bruxism2022

    • Author(s)
      Sarkar Avijite Kumer、Nakamura Shiro、Nakai Kento、Sato Taro、Shiga Takahiro、Abe Yuka、Hoashi Yurie、Inoue Tomio、Akamatsu Wado、Baba Kazuyoshi
    • Journal Title

      Stem Cell Research

      Volume: 59 Pages: 102658-102658

    • DOI

      10.1016/j.scr.2022.102658

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of an in vitro model for analyzing mitochondrial ultrastructure in PRKN-mutated patient iPSC-derived dopaminergic neurons2021

    • Author(s)
      Yokota Mutsumi、Kakuta Soichiro、Shiga Takahiro、Ishikawa Kei-ichi、Okano Hideyuki、Hattori Nobutaka、Akamatsu Wado、Koike Masato
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 58-58

    • DOI

      10.1186/s13041-021-00771-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells2021

    • Author(s)
      Nakai Kento、Shiga Takahiro、Yasuhara Rika、Sarkar Avijite Kumer、Abe Yuka、Nakamura Shiro、Hoashi Yurie、Kotani Keisuke、Tatsumoto Shoji、Ishikawa Hiroe、Go Yasuhiro、Inoue Tomio、Mishima Kenji、Akamatsu Wado、Baba Kazuyoshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15437-15437

    • DOI

      10.1038/s41598-021-95041-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of two iPSC lines from siblings of a homozygous patient with hearing loss and a heterozygous carrier with normal hearing carrying p.G45E/Y136X mutation in GJB22021

    • Author(s)
      Fukunaga Ichiro、Oe Yoko、Danzaki Keiko、Ohta Sayaka、Chen Cheng、Iizumi Madoka、Shiga Takahiro、Matsuoka Rina、Anzai Takashi、Hibiya-Motegi Remi、Tajima Shori、Ikeda Katsuhisa、Akamatsu Wado、Kamiya Kazusaku
    • Journal Title

      Stem Cell Research

      Volume: 53 Pages: 102290-102290

    • DOI

      10.1016/j.scr.2021.102290

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 細胞老化を誘導する化合物の同定と高齢発症神経変性疾患iPS細胞モデルへの活用2023

    • Author(s)
      志賀 孝宏
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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