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Establishment of a novel therapy for hemiplegia through repair pathways of Reelin/Disabled/GSK3.

Research Project

Project/Area Number 18K09009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Takai Kenji  聖マリアンナ医科大学, 医学部, 教授 (60121167)

Co-Investigator(Kenkyū-buntansha) 鈴木 登  聖マリアンナ医科大学, 医学部, 教授 (40235982)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords大脳皮質運動野損傷 / 片麻痺 / 細胞移植治療 / ニューロスフェア / Reelin / Disabled1 / yotariマウス / 神経再生 / ヒトiPS由来神経前駆細胞 / 片麻痺モデルマウス / 1次運動神経 / ヒトiPS由来神経細胞 / SDF1
Outline of Final Research Achievements

Although the number of patients with cerebrovascular disease in Japan has been decreasing in recent years, it has exceeded 1 million, and 20,000 new cases are seen every year. It requires rehabilitation and long-term care, which is a burden on the person and society, and the current treatment method: suppression of acute neurodegeneration does not change. Therefore, we conducted a mouse transplantation experiment to see if radical treatment could be performed by transplanting neural stem/progenitor cells (NSPCs) derived from human iPS cells or mouse neurosphere constituent cells. The motor area of the cerebral cortex was experimentally damaged to cause hemiplegia, and when NSPCs were transplanted into the striatum below the injured area, motor function was restored. To explore this mechanism, we focused on Reelin, which plays an important role in the developmental stage of the cerebral cortex, and confirmed that it is also involved in nerve regeneration in adult mice.

Academic Significance and Societal Importance of the Research Achievements

脳血管疾患に対して、ヒトiPS細胞由来あるいはマウスニューロスフェア細胞などの神経前駆細胞(NSPCs)の移植によって根治的治療を行えないか、マウスの移植実験を行った。疾患モデルは、マウスの大脳皮質運動野の凍結損傷とし、移植細胞としてはヒトiPS細胞、あるいはマウスニューロスフェアを用いた。iPS細胞を用いることは、ES細胞を用いることに対する免疫学的・倫理的問題や細胞ソースの問題をクリアできる。マウスニューロスフェア細胞については、移植細胞とした場合、回復過程の起点と考えられるDab1遺伝子knockoutマウスに相当するyot/yotマウスを用いて、これと比較が出来るという理由による。

Report

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

    (6 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Defective Reelin/Dab1 signaling pathways associated with disturbed hippocampus development of homozygous yotari mice.2021

    • Author(s)
      Arimitsu N, Mizukami Y, Shimizu J, Takai K, Suzuki T, Suzuki N
    • Journal Title

      Molecular and Cellular Neuroscience

      Volume: 112 Pages: 103614-103614

    • DOI

      10.1016/j.mcn.2021.103614

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between SDF1 and CXCR4 Promotes Photoreceptor Differentiation via Upregulation of NFκB Pathway Signaling Activity in Pax6 Gene-Transfected Photoreceptor Precursors.2020

    • Author(s)
      Shimizu J, Suzuki T, Hirotsu C, Ueno H, Takada E, Arimitsu N, Ueda Y, Wakisaka S, Suzuki N.
    • Journal Title

      Ophthalmic Res.

      Volume: 14 Issue: 4 Pages: 1-12

    • DOI

      10.1159/000503929

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elucidation of predictors of disease progression in patients with relapsing polychondritis at the onset: potential impact on patient monitoring.2020

    • Author(s)
      Shimizu J, Yamano Y, Kawahata K, Suzuki N
    • Journal Title

      BMC Rheumatolgy

      Volume: 4 Issue: 1 Pages: 41-41

    • DOI

      10.1186/s41927-020-00141-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Reelin/Disabled1 pathway on functional recovery of hemiplegic mice after neural cell transplantation; Reelin promotes migration toward motor cortex and maturation to motoneurons of neural grafts.2019

    • Author(s)
      Arimitsu N, Takai K, Fujiwara N, Shimizu J, Ueda Y, Wakisaka S, Hirotsu C, Murayama M A, Suzuki T, Suzuki N
    • Journal Title

      Exp Neurol

      Volume: 320 Pages: 112970-112970

    • DOI

      10.1016/j.expneurol.2019.112970

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet's disease.2019

    • Author(s)
      Shimizu J, Kubota T, Suzuki N et al.
    • Journal Title

      Clinical Rheumatology

      Volume: 9 Issue: 5 Pages: 1-9

    • DOI

      10.1007/s10067-018-04419-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Motor function recovery in hemiplegic mice after neural stem/progenitor cells transplantation.2019

    • Author(s)
      Arimitsu N, Takai K, Hirotsu C, Shimizu J, Suzuki N
    • Organizer
      International Society for Stem Cell Research 2019 Annual Meeting Los Angeles, California, USA
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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