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The role of nerve-vascular wiring and perivascular stem cells in peripheral nerve regeneration

Research Project

Project/Area Number 19K16905
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionAsahikawa Medical College

Principal Investigator

TOMITA YUI  旭川医科大学, 大学病院, 助教 (50836450)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords末梢神経再生 / NG2 / Ninjurin1 / 神経血管ワイヤリング / シュワン細胞 / Ninjurin
Outline of Research at the Start

先行実験で毛細血管を構成する周細胞の一部に神経分化能を持つ幹細胞(CapSCs)、さらに同細胞のシュワン細胞分化能を制御する因子(Ninjurin1 (Ninj1))を見出した。このことから、「CapSCsは、Ninj1を介して血管周囲でシュワン細胞に分化し、神経軸索再生を促す」という仮説をたて、周細胞特異的にNinj1欠損を誘導するマウスの坐骨神経障害モデルなどを利用して検証していくことにより、神経血管伴走化の機序、さらに末梢神経の機能維持や再生の機序解明を目指す。

Outline of Final Research Achievements

Ninjurin 1 (Ninj1) was originally identified as a protein induced by peripheral nerve injury. Schwann cells (SCs) and microvasculature are critical for peripheral nerve regeneration. Recent studies including ours have shown that some perivascular mural cells (PCs) are multipotent and contribute to tissue regeneration as a source of regenerative cells. Multipotent PCs, namely capillary stem cells (CapSCs) have a high potential to differentiate into neuronal lineages. Nerve/glial antigen 2 (NG2)-positive cells are recognized as immature Schwann cells and microvascular pericytes (PCs) in the peripheral nervous system.
In this study, we investigated the role of Ninj1 in peripheral nerve regeneration using NG2-Ds red mice, NG2+cell-specific inducible deletion of Ninj1 mice, SC cell lines, and CapSC cell lines.
We demonstrated that Ninj1 plays an important role particularly in the myelination process of regenerating nerves through NG2 positive cells including CapSCs.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会を背景に増加する多くの難治性慢性疾患の病態に末梢神経系の異常が関連していることが知られているが、末梢神経の機能維持や再生システムの知見は限られている。末梢神経は毛細血管と伴走し、その機能維持や再生に密接に関与していることが知られているが、神経と血管の伴走化がどのように成立するのかという根本的な課題は解明されていない。本研究では「神経に伴走する毛細血管」や「毛細血管に局在する新規の幹細胞」に着目し、末梢神経の髄鞘化にNinjurin1が重要な役割を示すことを示した。末梢神経再生の機序解明および治療法の開発につながると期待される。

Report

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

    (7 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Pericyte-specific deletion of Ninjurin-1 induces fragile vasa vasorum formation and enhances intimal hyperplasia of injured vasculature2021

    • Author(s)
      Kiwamu Horiuchi, Kohei Kano, Akiho Minoshima, Taiki Hayasaka, Atsushi Yamauchi, Takamitsu Tatsukawa, Risa Matsuo, Yuri Yoshida, Yui Tomita, Maki Kabara, Naoki Nakagawa, Naofumi Takehara, Naoyuki Hasebe, and Jun-ichi Kawabe
    • Journal Title

      American Journal of Physiology Heart and Circulatory Physiology

      Volume: - Issue: 6 Pages: H2438-H2447

    • DOI

      10.1152/ajpheart.00931.2020

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] EphA7+ perivascular cells as myogenic and angiogenic precursors improving skeletal muscle regeneration in a muscular dystrophic mouse model2020

    • Author(s)
      Kano Kohei、Horiuchi Kiwamu、Yoshida Yuri、Hayasaka Taiki、Kabara Maki、Tomita Yui、Tatsukawa Takamitsu、Matsuo Risa、Sawada Jun、Nakagawa Naoki、Takehara Naofumi、Hasebe Naoyuki、Kawabe Jun-ichi
    • Journal Title

      Stem Cell Research

      Volume: 47 Pages: 101914-101914

    • DOI

      10.1016/j.scr.2020.101914

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ninjurin 1 mediates peripheral nerve regeneration through Schwann cell maturation of NG2-positive cells2019

    • Author(s)
      Tomita Yui、Horiuchi Kiwamu、Kano Kohei、Tatsukawa Takamitsu、Matsuo Risa、Hayasaka Taiki、Yoshida Yuri、Kabara Maki、Yasuda Satoshi、Nakajima Keiichi、Nakagawa Naoki、Takehara Naofumi、Okizaki Atsutaka、Hasebe Naoyuki、Kawabe Jun-ichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 519 Issue: 3 Pages: 462-468

    • DOI

      10.1016/j.bbrc.2019.09.007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] EphA7陽性周細胞は、筋ジストロフィーモデルマウスの病態を改善する2020

    • Author(s)
      鹿野耕平、堀内 至、吉田有里、早坂太希、鹿原真樹、富田 唯、竜川貴光、松尾梨沙、安田 哲、澤田 潤、中川直樹、竹原有史、長谷部直幸、川辺淳一
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Transplantation of capillary stem cells improves skeletal muscle regeneration in muscular dystrophy.2020

    • Author(s)
      Kohei Kano, Kiwamu Horiuchi, Yuri Yoshida, Taiki Hayasaka, Maki Kabara, Yui Tomita, Takamitsu Tatsukawa, Risa Matsuo, Satoshi Yasuda, Jun Sawada, Naoki Nakagawa, Naofumi Takehara, Naoyuki Hasebe, and Jun-ichi Kawab
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Ninjurin1は、NG2陽性シュワン前駆細胞の成熟化を調整することにより末梢神経再生に関わる2019

    • Author(s)
      富田 唯
    • Organizer
      日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 毛細血管由来幹細胞、その用途、および、その製造方法2020

    • Inventor(s)
      川辺淳一
    • Industrial Property Rights Holder
      川辺淳一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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