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

Research Project

Project/Area Number 21K17887
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 63020:Radiation influence-related
Research InstitutionHirosaki 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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 / 致死線量放射線 / 放射線誘発組織障害 / TPO受容体作動薬 / 個体救命 / 組織修復幹細胞
Outline of Research at the Start

間葉系組織内に存在するMuse細胞は、自己複製能や多分化能に加えて腫瘍形成能を示さない多能性の組織修復幹細胞であり、幅広い疾患に対する細胞治療ソースとして注目されている。特に、傷害部位に遊走・生着し、環境に合わせた自発的分化により組織の修復と機能回復を担うことから、放射線被ばくによる急性放射線症候群、さらにはそれに起因する組織障害や機能不全に対する治癒効果が考えられるものの、Muse細胞の放射線応答や分泌小胞の特性、放射線誘発組織障害軽減作用等に関する報告は未だない。本研究では、放射線誘発組織障害に対するMuse細胞の致死回避や治癒・軽減効果と細胞から分泌される小胞の関与を検討する。

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.

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。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The Acute Radiation Syndrome-Mitigator Romiplostim and Secreted Extracellular Vesicles Improved Survival in Mice Acutely Exposed to Myelosuppressive Doses of Ionizing Radiation2023

    • Author(s)
      Yamaguchi Masaru、Kashiwakura Ikuo
    • Journal Title

      Biomolecules

      Volume: 13 Issue: 5 Pages: 837-837

    • DOI

      10.3390/biom13050837

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem/progenitor cells using integrated bioinformatics methods2023

    • Author(s)
      Sato Yoshiaki、Yoshino Hironori、Ishikawa Junya、Monzen Satoru、Yamaguchi Masaru、Kashiwakura Ikuo
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-023-37981-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune status of people living in the Tande-Tande sub-village (Indonesia), an area with high indoor radon concentration2023

    • Author(s)
      Purnami Sofiati、Ramadhani Dwi、Oktariyani Tiara Andalya、Suvifan Viria Agesti、Tetriana Devita、Sugoro Irawan、Rahajeng Nastiti、Wanandi Septelia Inawati、Wibowo Heri、Yamaguchi Masaru、Kashiwakura Ikuo、Syaifudin Mukh、Widowati Retno
    • Journal Title

      Radiation and Environmental Biophysics

      Volume: 62 Issue: 4 Pages: 449-463

    • DOI

      10.1007/s00411-023-01047-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative Modification Status of Human Serum Albumin Caused by Chronic Low-Dose Radiation Exposure in Mamuju, Sulawesi, Indonesia2022

    • Author(s)
      Yamaguchi Masaru、Tatara Yota、Nugraha Eka Djatnika、Tamakuma Yuki、Sato Yoshiaki、Miura Tomisato、Hosoda Masahiro、Yoshinaga Shinji、Syaifudin Mukh、Tokonami Shinji、Kashiwakura Ikuo
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 12 Pages: 2384-2384

    • DOI

      10.3390/antiox11122384

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum Proteomic and Oxidative Modification Profiling in Mice Exposed to Total Body X-Irradiation2022

    • Author(s)
      Yamaguchi Masaru、Tatara Yota、Nugraha Eka Djatnika、Sato Yoshiaki、Miura Tomisato、Hosoda Masahiro、Syaifudin Mukh、Tokonami Shinji、Kashiwakura Ikuo
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 9 Pages: 1710-1710

    • DOI

      10.3390/antiox11091710

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of biological responses to low-dose radiation in humans2022

    • Author(s)
      Yamaguchi Masaru、Tatara Yota、Nugraha Eka Djatnika、Ramadhani Dwi、Tamakuma Yuki、Sato Yoshiaki、Miura Tomisato、Hosoda Masahiro、Yoshinaga Shinji、Syaifudin Mukh、Kashiwakura Ikuo、Tokonami Shinji
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 184 Pages: 196-207

    • DOI

      10.1016/j.freeradbiomed.2022.04.006

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Analysis of the Serum Metabolomic Profile for the Radiomitigative Effect of the Thrombopoietin Receptor Agonist Romiplostim in Lethally Whole-Body-Irradiated Mice2022

    • Author(s)
      Sato Yoshiaki、Yamaguchi Masaru、Kashiwakura Ikuo
    • Journal Title

      Metabolites

      Volume: 12 Issue: 2 Pages: 161-161

    • DOI

      10.3390/metabo12020161

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of a Novel Small-molecule Interleukin-6 Inhibitor ThroughVirtual Screening Using Artificial Intelligence2022

    • Author(s)
      Sato Yoshiaki、Kashiwakura Ikuo、Yamaguchi Masaru、Yoshino Hironori、Tanaka Takeshi、Ikeda Ken、Ye Zhengmao、Komatsu Hirotsugu、Matsuzaki Takao、Hosoda Masato
    • Journal Title

      Medicinal Chemistry

      Volume: 18 Issue: 6 Pages: 694-700

    • DOI

      10.2174/1573406418666211116144243

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comprehensive exposure assessments from the viewpoint of health in a unique high natural background radiation area, Mamuju, Indonesia2021

    • Author(s)
      Eka Djatnika Nugraha, Masahiro Hosoda, Kusdiana, Untara, June Mellawati, Nurokhim, Yuki Tamakuma, Abarrul Ikram, Mukh Syaifudin, Ryohei Yamada, Naofumi Akata, Michiya Sasaki, Masahide Furukawa, Shinji Yoshinaga, Masaru Yamaguchi, Tomisato Miura, Ikuo Kashiwakura, Shinji Tokonami
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 14578-14578

    • DOI

      10.1038/s41598-021-93983-2

    • NAID

      120007170569

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] The acute radiation syndrome mitigator Romiplostim and secreted extracellular vesicles improved survival in mice acutely exposed to myelosuppressive doses of ionizing radiation2024

    • Author(s)
      Masaru Yamaguchi, Kashiwakura Ikuo
    • Organizer
      online seminar for graduate students to exchange their academic information in the fields of radiation protection and/or radiation medicine (biology)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism of action of the thrombopoietin receptor agonist romiplostim in reducing radiation injury.2023

    • Author(s)
      Masaru Yamaguchi, Kashiwakura Ikuo
    • Organizer
      The 17th International Congress for Radiation Research (ICRR2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The acute radiation syndrome mitigator Romiplostim and secreted extracellular vesicles improved survival in mice acutely exposed to myelosuppressive doses of ionizing radiation2023

    • Author(s)
      Masaru Yamaguchi, Kashiwakura Ikuo
    • Organizer
      韓国原子力医学院&台湾・長庚記念醫院&弘前大学合同セミナー
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Prediction of hub genes involved in radiation response of hematopoietic stem/progenitor cells derived from human placental/umbilical cord blood2023

    • Author(s)
      Yoshiaki Sato, Masaru Yamaguchi, Kashiwakura Ikuo
    • Organizer
      韓国原子力医学院&台湾・長庚記念醫院&弘前大学合同セミナー
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Radiation dose-dependent oxidative modification response of serum albumin2023

    • Author(s)
      Masaru Yamaguchi, Kashiwakura Ikuo
    • Organizer
      韓国原子力医学院&台湾・長庚記念醫院&弘前大学合同セミナー
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Detection of biological responses to low-dose radiation in humans2023

    • Author(s)
      Masaru Yamaguchi, Kashiwakura Ikuo, et al.
    • Organizer
      第60回日本放射線腫瘍学会生物部会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細胞外小胞がもたらす致死線量放射線ばく露個体救命効果の基礎的検討2022

    • Author(s)
      山口平
    • Organizer
      日本放射線腫瘍学会 第59回生物部会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ヒト血清タンパク質の酸化修飾に着目した慢性低線量放射線被ばく線量の検出2022

    • Author(s)
      山口平
    • Organizer
      日本放射線影響学会第65回大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Radio-mitigative effect of domestically approved drug Romiplostim and Extracellular Vesicles on mice exposed to lethal high-dose ionizing radiation2021

    • Author(s)
      Masaru Yamaguchi
    • Organizer
      2021 KIRAMS-Hirosaki University Webinar on Radiation Emergency Medicine
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 致死線量放射線ばく露個体に対する国内承認薬ロミプロスチム及び 細胞外小胞の放射線緩和効果2021

    • Author(s)
      山口平
    • Organizer
      日本放射線影響学会第64回大会
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 放射線被ばくバイオマーカー及び治療剤2022

    • Inventor(s)
      山口平、柏倉幾郎
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-201663
    • Filing Date
      2022
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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