Search for extracellular vesicles that contribute to the reduction of radiation-induced tissue damage and application to radiation emergency medicine

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18K18190
• Research Institution: Hirosaki University
• Principal Investigator: 山口 平 弘前大学, 保健学研究科, 助教 (00782822)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 細胞外小胞 / 致死線量放射線 / 急性放射線症候群 / TPO受容体作動薬 / 個体救命

Outline of Annual Research Achievements

本研究では、細胞外小胞の体内循環情報伝達物資としての性質を活用し、全身放射線曝露個体に組織障害軽減や致死回避をもたらす薬剤投与により血中で増加する細胞外小胞を探索・特定し、それら細胞外小胞の放射線障害軽減作用を評価する事で今後の新たな放射線リスクの防護に資する事を目的としている。本年度は、マウスに致死線量全身照射後、放射線緩和剤としてTPO受容体作動薬を照射直後から腹腔内投与し、経時的に生存マウスを麻酔下で採血後、血清中のエクソソーム（Exo）及びLarge Extracellular vesicles （LEVs）を回収した。続いて、新たに用意したマウスに対して致死線量全身照射後、Exo及びLEVs抽出液を生理食塩水で10^7 ~ 10^8 particles/100 μlとなるように調製し、照射後30分以内から1日1回3日間連続で腹腔内投与（100 μl/回）を行い、30日間生存率を指標として細胞外小胞がもたらす致死線量放射線ばく露個体の救命効果を検討した。放射線照射細胞外小胞非投与群では2週間程度で全個体の死亡が認められた。一方、照射後14日目に回収したExo又はLEVs投与群では、照射20日目前後から個体の死亡が確認されたものの、30日間生存率は両群ともに50%であった。照射後21日目に回収したExo又はLEVs投与群では、30日間生存率はそれぞれ50%及び75%まで改善した。照射後30日目に回収したLEVs投与群では照射後14日目には全個体の死亡が認められた一方で、Exo投与群の30日間生存率は75%であった。これらの結果から、放射線障害軽減/致死回避個体から回収した細胞外小胞により、致死線量放射線ばく露個体に障害軽減作用や救命効果がもたらされる可能性が示唆された。

Research Products

• [Journal Article] A unique high natural background radiation area ? Dose assessment and perspectives (2021)
  • Author(s): Hosoda Masahiro, Nugraha Eka Djatnika, Akata Naofumi, Yamada Ryohei, Tamakuma Yuki, Sasaki Michiya, Kelleher Kevin, Yoshinaga Shinji, Suzuki Takahito, Rattanapongs Chanis Pornnumpa, Furukawa Masahide, Yamaguchi Masaru, et al.
  • Journal Title: Science of The Total Environment Volume: 750 Pages: 142346～142346
  • DOI: 10.1016/j.scitotenv.2020.142346
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Discriminative Measurement of Absorbed Dose Rates in Air from Natural and Artificial Radionuclides in Namie Town, Fukushima Prefecture (2021)
  • Author(s): Ogura Koya, Hosoda Masahiro, Tamakuma Yuki, Suzuki Takahito, Yamada Ryohei, Negami Ryoju, Tsujiguchi Takakiyo, Yamaguchi Masaru, Shiroma Yoshitaka, Iwaoka Kazuki, Akata Naofumi, Shimizu Mayumi, Kashiwakura Ikuo, Tokonami Shinji
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 18 Pages: 978～978
  • DOI: 10.3390/ijerph18030978
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of Antioxidant Stress-Responsive Transcription Factor Nrf2 Target Gene in the Reduction of Radiation Damage by the Thrombocytopenia Drug Romiplostim (2020)
  • Author(s): Chiba Akane、Kawabata Nanami、Yamaguchi Masaru、Tokonami Shinji、Kashiwakura Ikuo
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 43 Pages: 1876～1883
  • DOI: 10.1248/bpb.b20-00442
  • Peer Reviewed / Open Access
• [Journal Article] Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome (2020)
  • Author(s): Yamaguchi Masaru、Suzuki Marino、Funaba Moeri、Chiba Akane、Kashiwakura Ikuo
  • Journal Title: Stem Cell Research & Therapy Volume: 11 Pages: 339
  • DOI: 10.1186/s13287-020-01861-x
  • Peer Reviewed / Open Access
• [Journal Article] Proteomic changes by radio-mitigative thrombopoietin receptor agonist romiplostim in the blood of mice exposed to lethal total-body irradiation (2020)
  • Author(s): Nishida Teruki、Yamaguchi Masaru、Tatara Yota、Kashiwakura Ikuo
  • Journal Title: International Journal of Radiation Biology Volume: 96 Pages: 1125～1134
  • DOI: 10.1080/09553002.2020.1787546
  • Peer Reviewed / Open Access
• [Presentation] Research activities related to the radiation biodosimetry and reduction of radiation-induced disorders (2020)
  • Author(s): M. Yamaguchi, I. Kashiwakura
  • Organizer: 2020 KIRAMS - Hirosaki University Webinar on Radiation Emergency Medicine
  • Int'l Joint Research / Invited
• [Presentation] Development of e-learning materials of the trauma treatment for the patients with radioactive contamination (2020)
  • Author(s): T. Koiwa, M. Narita, M. Sakamoto, Y. Suzuki, K. Narumi, K. Yamanouchi, M. Yamaguchi, T. Tsujiguchi, K. Ito, E. Tsuruga
  • Organizer: The 3rd Workshop on Radiation Research and Its Related Issue 2020 & The 7th Educational Symposium on RADIATION and HEALTH by young scientists (ESRAH2020)
  • Int'l Joint Research
• [Presentation] Regulation of antioxidant stress-responsive transcription factor Nrf2 target gene in the reduction of radiation damage by the thrombocytopenia drug Romiplostim (2020)
  • Author(s): A Chiba, M yamaguchi, I Kashiwakura
  • Organizer: The 3rd Workshop on Radiation Research and Its Related Issue 2020 & The 7th Educational Symposium on RADIATION and HEALTH by young scientists (ESRAH2020)
  • Int'l Joint Research