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Research on regenerative treatment of traumatic brain injury by combining neural stem cell transplantation and neurite outgrowth-promoting compounds

Research Project

Project/Area Number 22K16696
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionKeio University

Principal Investigator

Yoshitaka Kase  慶應義塾大学, 医学部(信濃町), 特任講師 (00830655)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords神経幹細胞 / 神経細胞 / 脳挫傷 / 神経再生 / 再生治療 / iPS細胞 / ニューロン / 神経軸索 / 再生医療 / γ-secretase inhibitor
Outline of Research at the Start

申請者が発見し、特許申請済みの神経突起伸長効果を有する化合物RK-682とγ-secretase inhibitorの中でも特に神経幹細胞からニューロンへ分化させる作用の強いCompound 34を添加したhiPSC-NS/PCを損傷箇所に移植し、これまでに報告のない欠損した脳のニューロンネットワークをも再構築させた脳組織レベルでの回復を促す。そして運動機能障害と高次脳機能障害の両面の回復を達成させる。

Outline of Final Research Achievements

Traumatic brain injuries, such as cerebral contusions, often result from car accidents or other external impacts, leading to irreversible damage to brain tissue.
In response to this challenge, our study sought to explore regenerative therapy in a mouse model of brain contusion. Our approach involved combining insights from regenerative research on spinal cord injury treatment, utilizing human-induced pluripotent stem cell-derived neural stem/progenitor cell transplantation, with a compound identified by the principal investigator for its neurite outgrowth-promoting properties.
We transplanted human-induced pluripotent stem cell-derived neural stem/progenitor cells along with a neurite outgrowth-promoting compound to the site of brain contusion injury in mice, successfully promoting recovery at the tissue level in the damaged brain.

Academic Significance and Societal Importance of the Research Achievements

外傷性脳損傷は交通事故やその他の外的衝撃により引き起こされ、基本的に一度損傷した脳組織は再生することはない。交通事故などによる傷害により外傷性脳損傷を受傷し脳機能障害をきたすと、救命はできたとしても、その後の生活様式は一変してしまう。
そもそも脳挫傷は、脳梗塞に比べて組織自体が欠損してしまうため、再生がより困難という背景もあり、脳挫傷の再生治療研究は脳梗塞に比べるとその報告数は圧倒的に少ないのが現状であり、これまで、外傷による脳組織の欠損自体を回復させ、運動機能に加え、高次脳機能障害をも回復させた報告はなかったため、本研究は意義あるものである。

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (5 results)

All 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] A set-theoretic definition of cell types with an algebraic structure on gene regulatory networks and application in annotation of RNA-seq data.2023

    • Author(s)
      Okano Y, Kase Y, Okano H.
    • Journal Title

      Stem Cell Reports.

      Volume: 18 Issue: 1 Pages: 113-130

    • DOI

      10.1016/j.stemcr.2022.10.015

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The GADD45G/p38 MAPK/CDC25B signaling pathway enhances neurite outgrowth by promoting microtubule polymerization2022

    • Author(s)
      Yoshitaka kase, Tsukika Sato, Yuji Okano, Hideyuki Okano
    • Journal Title

      iSicence

      Volume: 25 Issue: 4 Pages: 104089-104089

    • DOI

      10.1016/j.isci.2022.104089

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヒトのニューロンにおける神経突起伸長メカニズムの解析2022

    • Author(s)
      加瀬義高
    • Journal Title

      神経化学 (Bulletin of Japanese Society for Neurochemistry )

      Volume: 61 Pages: 96-100

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Presentation] 神経再生医学の最前線 ー細胞移動・軸索伸展から機能回復までー 神経突起伸展の分子機構と脊髄損傷および 外傷性脳損傷の再生医療への応用2023

    • Author(s)
      加瀬義高
    • Organizer
      第22回 日本再生医療学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] The GADD45G/p38 MAPK/CDC25B signaling pathway enhances neurite outgrowth by promoting microtubule polymerization2022

    • Author(s)
      加瀬義高
    • Organizer
      第43回日本炎症・再生医学会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2025-01-30  

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