Elucidation of the role of MRC1 macrophages after peripheral nerve injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16758
• 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: Matsui Yuki 北海道大学, 医学研究院, 客員研究員 (60908193)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 末梢神経損傷 / マクロファージ / 軸索再生

Outline of Final Research Achievements

Using a rat sciatic nerve crush injury and transection injury models, the current study identified that the locations of MRC1 macrophages were associated with the tips of regenerating axons. Furthermore, when MRC1 macrophages were depleted using mannosylated clodronate liposome, axon regeneration after rat sciatic nerve crush injury was impaired. Moreover, when MRC1 like macrophages were created by the stimulation with IL4, uPA secreted by them has an axon regeneration effect, and the axon regeneration effect of MRC1 like macrophages disappears when the uPA gene is deleted. Lastly, syngeneic Mrc1 like macrophages have an axon regeneration effect, whereas the axon regeneration effect is significantly attenuated in allogeneic Mrc1 like macrophages, suggesting that Mrc1 like macrophages needs to be autograft rather than allograft for clinical application.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

マクロファージが末梢神経損傷の修復機転の主たる細胞の一つであることは判明していたが、その亜種の一つが、軸索再生に直接関わっていることが判明した。特に、軸索の先端部位に集積し、その再生を支持していたことから、末梢神経の修復機転における高度な細胞相互作用が具体的に解明された。さらに、今回、マクロファージが発現するuPAが軸索再生効果を持ち、分子治療に応用できる可能性を示した。さらに、MRC1マクロファージ移植を臨床応用する際には、自家移植でなくては効果を発揮できないことを同定し、MRC1マクロファージ移植の現実的な応用には限界があることも明らかにした。