Identification of optimal fibroblasts for peripheral nerve regeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18016
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido University
• Principal Investigator: Endo Takeshi 北海道大学, 大学病院, 助教 (50849148)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 線維芽細胞 / 軸索再生 / 末梢神経損傷

Outline of Final Research Achievements

The current study investigated the capacity of fibroblasts (Fb) derived from peripheral nerves to stimulate the neurite outgrowth of DRG neurons and clarified their molecular characteristics. The Fb derived from epineurium (Fb-Epn) showed the greatest neurite outgrowth, followed by the Fb derived from parenchyma, indicating that nerve-derived Fb promote neurite outgrowth more effectively than skin-derived Fb. In in vivo, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb-Epn might be involved more than was previously thought in axon regeneration after PNI.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、末梢神経由来Fbは皮膚由来Fbよりも神経突起伸長能に優れ、中でも神経上膜由来Fbが神経実質由来Fbよりも優れていること、Fbは神経組織内の局在によって分子的・機能的に異なること、神経上膜由来Fbが末梢神経損傷後の軸索再生に関与している可能性を示し、末梢神経内の局在の異なるFbは、異なる機能を有するという仮説を支持した。Fbは一般的に調製や増殖が容易であることから、細胞治療の材料として探索されてきたが、本研究の知見は、神経組織特異的Fbはこれらの細胞治療材料としての可能性を示している。