Analysis of extracellular vesicles derived from microvascular endothelial cells: towards the development of treatment for cerebral white matter infarction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Gunma University
• Principal Investigator: Kurachi Masashi 群馬大学, 大学院医学系研究科, 助教 (20271546)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血管内皮細胞 / 細胞外小胞 / エクソソーム / オリゴデンドロサイト前駆細胞 / 神経科学 / 再生医学 / 認知症 / 脳白質障害

Outline of Final Research Achievements

I found that fibronectin (FN) was abundant on the surface of extracellular vesicles derived from brain microvascular endothelial cells (MVEC-EVs) and that FN on EVs mediated their internalization into oligodendrocyte precursor cells (OPCs) by its binding to heparan sulfate proteoglycan (HSPG) on OPCs. OPC survival and proliferation promoted by EVs were attenuated by blocking the internalization of EVs into OPCs. Moreover, I also found that platelet-derived growth factor-B (PDGF-B) was on the surface of MVEC-EVs and that PDGF-B was tethered to the EV by HSPG. The neutralizing antibody against PDGF-B significantly reduced the promoting activity of MVEC-EVs on OPC proliferation, suggesting that PDGF-B on the surface of MVEC-EV promotes OPC proliferation.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

微小血管内皮細胞由来細胞外小胞の表面にフィブロネクチン、血小板由来成長因子PDGF-Bが存在すること、小胞内にrno-miR-21-5pなどのマイクロRNAが含まれることを明らかにした。また、細胞外小胞表面のPDGF-BBがオリゴデンドロサイト前駆細胞の増殖を促進することを明らかにした。これらの知見は、運動機能や認知機能の障害に関わる白質病変の改善に向けた治療戦略の構築に有用であると考えられる。