The role of nerve-vascular wiring and perivascular stem cells in peripheral nerve regeneration
| Project/Area Number |
19K16905
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
TOMITA YUI 旭川医科大学, 大学病院, 助教 (50836450)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| 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 |
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| 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。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(7 results)
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[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
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Journal Title
American Journal of Physiology Heart and Circulatory Physiology
Volume: -
Issue: 6
Pages: H2438-H2447
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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