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Inhibiting Scar Development for Promoting Stem Cell Engraftment in Chronic Spinal Cord Injuries.

Research Project

Project/Area Number 16K21360
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Neurochemistry/Neuropharmacology
Research InstitutionKeio University

Principal Investigator

Renault-Mihara Francois  慶應義塾大学, 医学部(信濃町), 特任講師 (20570427)

Research Collaborator SON Iki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsSpinal cord injury / reactive astrocytes / glial scar / chronic scar / stem cell / STAT3 / RhoA / astrocytes / spinal cord injury / stat3 / gene regulation / 脊椎脊髄病学 / 幹細胞生物学 / 再生 / 修復
Outline of Final Research Achievements

#1: We found that molecule X, regulates the expression of several proteases and induces lesion remodeling after SCI, but the survival rate and distribution of transplanted neural stem cells are unchanged, which led us to abandon the theme. #2 The characterization of the gene expression profile of scar-forming reactive astrocytes has been reported by another research group (Hara M. et al., Nature Medicine, 2017). #3: We found that the transcription factor STAT3 regulates the dynamics of reactive astrocytes in vitro and glial scar formation in vivo. This study was published in the Journal of Cell Biology (Renault-Mihara et al., 2017).#4: Two different experimental models were used to characterize novel markers of pathological nerve scars. Our hypothesis is those genes are associated with incomplete healing in the central nervous system. This study is still in progress.

Academic Significance and Societal Importance of the Research Achievements

Spinal cord injury is a major medical problem as all the surviving patients inevitably become chronic patients. Our research focusing on the mechanisms of scar formation and stabilization in the subacute and chronic phases respectively may help design new therapeutic strategies.

Report

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

    (7 results)

All 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury2018

    • Author(s)
      Kojima Kota、Miyoshi Hiroyuki、Nagoshi Narihito、Kohyama Jun、Itakura Go、Kawabata Soya、Ozaki Masahiro、Iida Tsuyoshi、Sugai Keiko、Ito Shuhei、Fukuzawa Ryuji、Yasutake Kaori、Renault-Mihara Francois、Shibata Shinsuke、Matsumoto Morio、Nakamura Masaya、Okano Hideyuki
    • Journal Title

      STEM CELLS Translational Medicine

      Volume: 8 Issue: 3 Pages: 260-270

    • DOI

      10.1002/sctm.18-0096

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STAT3: Down the R(h)oAd2018

    • Author(s)
      Renault-Mihara F, Okano H
    • Journal Title

      Cytokine

      Volume: 102 Pages: 149-150

    • DOI

      10.1016/j.cyto.2017.08.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] STAT3: Down the R(h)oAd.2018

    • Author(s)
      Renault-Mihara F, Okano H
    • Journal Title

      Cytokine

      Volume: 102 Pages: 149-150

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations2017

    • Author(s)
      Okuno H, Renault Mihara F, Ohta S, Fukuda K, Kurosawa K, Akamatsu W, Sanosaka T, Kohyama J, Hayashi K, Nakajima K, Takahashi T, Wysocka J, Kosaki K, Okano H.
    • Journal Title

      elife

      Volume: 6 Pages: 23-24

    • DOI

      10.7554/elife.21114

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STAT3-regulated RhoA drives reactive astrocyte dynamics.2017

    • Author(s)
      Renault-Mihara F, Okano H
    • Journal Title

      Cell Cycle.

      Volume: 16 Pages: 1995-1996

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulation of RhoA by STAT3 coordinates glial scar formation.2017

    • Author(s)
      Renault-Mihara F, Mukaino M, Shinozaki M, Kumamaru H, Kawase S, Baudoux M, Ishibashi T, Kawabata S, Nishiyama Y, Sugai K, Yasutake K, Okada S, Nakamura M, Okano H.
    • Journal Title

      J Cell Biol

      Volume: 216 Pages: 2533-2550

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Regulation of RhoA by STAT3 coordinates glial scar formation.2017

    • Author(s)
      Francois Renault-Mihara
    • Organizer
      American Society of Cell Biology/European Molecular Biology Organization) 2017 meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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