Elucidation of mitochondrial regulation and actin dynamics of umbilical cord-derived mesenchymal cells on microglia

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22892
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Mukai Takeo 東京大学, 医学部附属病院, 助教 (60871324)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 臍帯由来間葉系細胞 / ミクログリア / アクチンダイナミクス / ミトコンドリア

Outline of Final Research Achievements

We analyzed the changes in characteristics of umbilical cord-derived mesenchymal cells (UC-MSC) on LPS-activated microglial primary cultures. It was demonstrated that the inflammatory cytokine NFκB pathway of activated microglia was significantly reduced by UC-MSC, and that the reduced phagocytic ability and actin dynamics were improved by UC-MSC co-culture. We also demonstrated that cdc42 and Rac1 were significantly elevated in UC-MSC as the mechanism of these phenomena, which was contributed by the activation of the PI3K / Akt-Rho GTPase pathway. LPS stimulation did not significantly change the degree of mitochondrial depolarization.

Free Research Field

新生児学

Academic Significance and Societal Importance of the Research Achievements

UC-MSCが活性化ミクログリアに及ぼす形態変化・貪食能変化とそのメカニズムをアクチンダイナミクスの観点から解明した比較実験はなく、本研究が国内外初となる。従って本研究は損傷脳組織において活性型ミクログリアを鎮静化させる新規治療の基盤となり、将来のMSCを用いた細胞治療へと繋がる可能性を示すと考えられる。