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2018 年度 実績報告書

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

研究課題

研究課題/領域番号 16K21360
研究機関慶應義塾大学

研究代表者

ルノー三原 フランソワ  慶應義塾大学, 医学部(信濃町), 特任講師 (20570427)

研究期間 (年度) 2016-04-01 – 2019-03-31
キーワードSpinal cord injury / reactive astrocytes / glial scar / chronic scar / stem cell / STAT3 / RhoA
研究実績の概要

#1: Effects of molecule X in spinal cord injury. We found that molecule X, regulates the expression of several proteases and induces lesion remodeling, but the survival rate and distribution of transplanted neural stem cells are unchanged, which led us to abandon this research theme.
#2 The characterization of the gene expression profile of lesion scar-forming reactive astrocytes has been reported by another Japanese research group (Hara M. et al., Nature Medicine, 2017 Jul;23(7):818-828) before we could complete our own study.
#3: We found that the transcription factor STAT3 regulates the dynamics of reactive astrocytes in vitro and glial scar formation in vivo. We have shown that regulation of the GTPase RhoA by STAT3 modulates glial scar formation in vivo. This study is published in the Journal of Cell Biology (Renault-Mihara et al., 2017, PMID: 28642362).
#4: Central nervous system healing mechanisms. Two different experimental models were used to characterize novel markers of pathological nerve scars. This marker is not seen in simulated animals. Interestingly, this marker is also expressed in wild-type mice in the chronic phase of spinal cord injury, which may indicate that this marker is useful in the study of the incomplete healing that characterizes neural tissue. By comparing gene expression levels in these different models, we are trying to identify candidate genes responsible for the emergence of this marker. Our hypothesis is that these genes may be associated with incomplete healing in the central nervous system. This study is still in progress.

備考

The research done is somehow different from the proposed project, but has brought significant results in directly related areas (glial scar after spinal cord injury, and markers of chronic scars).

  • 研究成果

    (3件)

すべて 2019 2018

すべて 雑誌論文 (3件) (うち国際共著 3件、 査読あり 3件)

  • [雑誌論文] Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury.2019

    • 著者名/発表者名
      Kojima K, Miyoshi H, Nagoshi N, Kohyama J, Itakura G, Kawabata S, Ozaki M, Iida T, Sugai K, Ito S, Fukuzawa R, Yasutake K, Renault-Mihara F, Shibata S, Matsumoto M, Nakamura M, Okano H
    • 雑誌名

      Stem Cells Transl Med

      巻: 8 ページ: 260-270

    • DOI

      doi: 10.1002/sctm.18-0096

    • 査読あり / 国際共著
  • [雑誌論文] CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations.2018

    • 著者名/発表者名
      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.
    • 雑誌名

      Elife

      巻: 6 ページ: 23-24

    • DOI

      doi: 10.7554/eLife.21114

    • 査読あり / 国際共著
  • [雑誌論文] STAT3: Down the R(h)oAd2018

    • 著者名/発表者名
      Renault-Mihara F, Okano H
    • 雑誌名

      Cytokine

      巻: 102 ページ: 149-150

    • DOI

      doi: 10.1016/j.cyto.2017.08.003

    • 査読あり / 国際共著

URL: 

公開日: 2019-12-27  

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