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Transplantation of iPS cell derived motoneuron precursors to damaged motor cortex

Research Project

Project/Area Number 16K10744
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Ueda Yuji  聖マリアンナ医科大学, 医学部, 講師 (00223470)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords皮質運動神経 / Reelin / 片麻痺 / 神経細胞移植 / ニューロスフェア / Disabled1 / 再生医学 / 移植・再生医療
Outline of Final Research Achievements

We previously reported that human iPS cell-derived neurons transplanted to hemiplegic mice improved their motor function. Reelin is a giant protein that helps control nerve cell migration and formation of motor cortex layer structures. In our transplantation, the transplanted cells produced Reelin and resulted in nerve tissue repair. At the same time, the transplanted cells expressed Reelin's receptor and caused phosphorylation of Disabled1 located downstream thereof. Subsequently, neurons expressed adhesion molecules integrin and N cadherin, and reconstructed neural networks in the injured cortex. These results indicate that Reelin plays an important role in histologic repair and functional recovery in neural cell transplantation into hemiplegic animal models.

Academic Significance and Societal Importance of the Research Achievements

脳卒中では多くの患者さんがその後遺症と戦っている。我々が研究を進めているリーリンは神経細胞の移動と運動皮質の層構造形成の制御を補助する巨大蛋白質として同定され、現在では神経の機能発現に重要に関わることが知られている。統合失調症、自閉症をはじめとした種々の中枢神経系の関わる疾患で異常を示す。
我々の実施した片麻痺モデルマウスに神経細胞移植を行う実験系においても、炎症細胞と移植細胞はリーリンを産生していた。この産生されたリーリンはオートクリンとパラクリンの両者のメカニズムで神経組織修復をもたらした。今後、神経細胞移植と共にリーリンを投与することが、神経機能の修復をもたらす可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (1 results)

All 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Neuronal cell sheets of cortical motor neuron phenotype derived from human iPS cells.2017

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

      Cell Transplant.

      Volume: 26 Issue: 8 Pages: 1355-1364

    • DOI

      10.1177/0963689717720280

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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