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Neural regeneration and signal pathway after neural stem / progenitor cells transplantation in hemiplegic mice mice

Research Project

Project/Area Number 16K10743
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

Chieko Hirotsu  聖マリアンナ医科大学, 医学部, 研究技術員 (90647174)

Co-Investigator(Kenkyū-buntansha) 有光 なぎさ  聖マリアンナ医科大学, 医学部, 助教 (40408688)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords神経 / 移動 / iPS / 神経細胞 / 移植 / 再生 / シグナル伝達 / 再生医療 / 細胞移植 / 神経再生 / 移植・再生医療 / 脳・神経 / 細胞・組織
Outline of Final Research Achievements

The hemiplegic mice whose motor cortex had been cryoinjured were subject to transplantation with NSPCs derived from human iPS cells. Another set of hemiplegic mice were injected with PBS as controls. This remedy for hemiplegia was evaluated by repeated beam walking tests and rotarod tests whether it was effective for recovery of their motor functions. To detect the grafted cells more clearly, we used human specific antibody staining. The grafts migrated from the striatum and reached to the injured cortex.The transplantation significantly improved their motor functions. The grafted cells distributed widely but appeared to have a tendency to accumulate predominantly near the damaged region at day 28. Reelin which regulated CNS development was expressed 1 day after cryogenic injury of right motor cortex.
Our results suggest that neurons or paracrine factor may become applicable for restoring the motor functions of patients suffering from hemiplegia.

Academic Significance and Societal Importance of the Research Achievements

中枢神経障害には現在、対症療法しかなく症状の悪化を緩和させることが治療の中心だが、神経細胞移植で脱落した神経を再生し根治への道が開ける点、発生過程での神経走行構造形成に関わる分泌性因子の関わりに着目した点に独創性がある。見出した因子は移植細胞が目的の部位に適した状態で的確に定着、分化できるよう補える作用を持つことから併用治療などによりさらなる効果が期待できる。さらに今回個体レベルにおける移植前後の生体内での挙動を検証することにより、神経前駆細胞の運命決定機構、定着機構、神経ネットワーク形成機構のより深い理解につながる点に意義がある。

Report

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

    (8 results)

All 2018 2017 2016

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 3 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
  • [Journal Article] Human iPS cell derived neural cell sheets exhibit mature neural and extendable scaffold functions and promote recovery in injured mouse spinal cords.2016

    • Author(s)
      Arimitsu N, Shimizu J, Iinuma M, Umehara T, Fujiwara N, Takai K, Wakisaka S, Hirotsu C, Suzuki T, Beppu M, Niki H, Suzuki N.
    • Journal Title

      J Stem Cell Res Med.

      Volume: 1 Issue: 2 Pages: 41-47

    • DOI

      10.15761/jscrm.1000106

    • Related Report
      2016 Research-status Report
    • Open Access
  • [Presentation] NEURAL REGENERATION MECHANISMS IN TRANSPLANTATION OF NEURONAL CELLS DERIVED FROM HUMAN INDUCED PLURIPOTENT STEM CELLS WITH THE EFFECT OF THEIR PARACRINE SECRETION.2018

    • Author(s)
      Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Naruyoshi Fujiwara, Chieko Hirotsu, Yoko Okada and Noboru Suzuki
    • Organizer
      International society for stem cell research 14th annual meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neural regeneration after transplantation of Neuronal cell sheet of cortical motor neuron phenotype.2018

    • Author(s)
      Nagisa Arimitsu-Nakata, Chieko Hirotsu,Kenji Takai, Jun Shimizu,Naruyoshi Fujiwara, Yoko Okada,Noboru Suzuki
    • Organizer
      the 5th TERMIS-WC 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reelin Signal Activation is Associated With Motor Function Recovery in the Neuron Transplantation of Hemiplegic Mice.2018

    • Author(s)
      Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Naruyoshi Fujiwara , Chieko Hirotsu, Yoko Okada , and Noboru Suzuki.
    • Organizer
      the 51st Winter Conference on Brain Research (WCBR) .
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS由来神経細胞移植による認知機能改善と改善メカニズムについての検討2017

    • Author(s)
      藤原成芳、岡田容子、 高井憲治、廣津千恵子、有光なぎさ、 高田えりか、清水潤、鈴木登.
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      宮城県仙台市(仙台国際センター)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 幹細胞由来神経細胞移植による脳損傷マウスにおける神経再生.2017

    • Author(s)
      有光なぎさ, 廣津千恵子, 高井憲治, 藤原成芳, 岡田容子, 清水潤, 鈴木登.
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      宮城県仙台市(仙台国際センター)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳損傷マウスに対する幹細胞由来神経細胞移植による神経再生.2016

    • Author(s)
      有光なぎさ, 廣津千恵子, 高井憲治, 藤原成芳, 清水潤, 鈴木登.
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      神奈川県横浜市(パシフィコ横浜)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report

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

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