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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16905
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Asahikawa 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
• Keywords: 末梢神経再生 / NG2 / Ninjurin1

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.

Free Research Field

末梢神経再生

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。