Mitigative effect of tissue repair stem cells and their secretory vesicles against radiation-induced tissue damage

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K17887
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Hirosaki University
• Principal Investigator: Yamaguchi Masaru 弘前大学, 保健学研究科, 助教 (00782822)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 急性放射線症候群 / 細胞外小胞 / マイクロRNA / 緊急被ばく医療 / 被ばく個体救命

Outline of Final Research Achievements

In cases of accidental high-dose total-body irradiation (TBI), acute radiation syndrome (ARS) can cause death. We investigated the radio-mitigative effects of extracellular vesicles (EV) on mice with severe ARS. C57BL/6 mice exposed to lethal TBI were treated with romiplostim (RP), and the EVs were isolated from the serum and intraperitoneally injected into other mice with severe ARS. The 30-day survival rate of lethal TBI mice drastically improved by 50-100% with the administration of EVs in the sera collected weekly from the mice in which radiation damage was alleviated and mortality was avoided by the administration of RP. Four responsive miRNAs showed significant expression changes in an array analysis. In particular, miR-144-5p was expressed only in the EVs of RP-treated TBI mice. Specific EVs may exist in the circulating blood of mice that escaped mortality with an ARS mitigator, and their endogenous molecules may be the key to the survival of mice with severe ARS.

Free Research Field

放射線科学、放射線生物学、放射線防護、被ばく医療

Academic Significance and Societal Importance of the Research Achievements

今後の原子力の安全利用や福島第一原発を含めた廃炉作業、将来の宇宙開発や核テロの脅威等に対し、放射線被ばくへの適切な医療安全対策は必須である。グローバルな観点からみても原子炉の数は増え続ける一方であり、人類は放射線事故や放射線被ばくのリスクと常に隣り合わせにある。細胞外小胞には、由来する細胞の種類に依存した多様な種類の分子が含まれ、放射線損傷又は障害軽減応答に特異的な分子が内在している可能性があり、生体内分子を緊急被ばく医療対策に応用することを視野に入れた新たなアプローチとなる。