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Development of liver regeneration therapy using super exosomes with multiple and high volume protein delivery systems

Research Project

Project/Area Number 22K19933
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionNiigata University

Principal Investigator

Tsuchiya Atsunori  新潟大学, 医歯学系, 准教授 (70464005)

Co-Investigator(Kenkyū-buntansha) 佐野 将之  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (80415687)
西村 健  筑波大学, 医学医療系, 教授 (80500610)
Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsエクソソーム / 間葉系幹細胞 / マクロファージ / 肝硬変 / 細胞外小胞
Outline of Research at the Start

日本で40万人程度が罹患する国民病の一つである肝硬変では、元々ある再生能力が低下するが、現在肝線維化改善・再生促進を誘導する薬はなく高いニーズがある。
今までの研究で肝臓内に集積し組織修復に関わるマクロファージを以下に良い状態に変化させるかが重要であることがわかっている。
今回我々は、間葉系幹細胞を改変し、そこから産生されてくるエクソソームをマクロファージに対して効果的に働く様に改変し、将来の治療薬となり得るか検討を行いたい。

Outline of Final Research Achievements

In this study, we succeeded in introducing tdTomato and Annexin A1 into exosomes, and confirmed that tdTomato is taken up by macrophages in large amounts in cirrhosis, providing basic data on the dynamics of exosomes for therapeutic purposes. In addition, the introduction of Annexin A1, which we consider to be one of the potential factors that may lead macrophages to become anti-inflammatory, was confirmed, but did not lead to a dramatic increase in therapeutic efficacy. Although there are issues to be addressed in the future, such as the possibility that a single protein was not sufficient and that the overall contents may have been altered, the establishment of the introduction system was very significant and provided fundamental data for the future.

Translated with DeepL.com (free version)

Academic Significance and Societal Importance of the Research Achievements

エクソソームは細胞培養上清から修飾を施さずにそのまま採取される天然型や特定の細胞株培養上清液や特定の動植物やその培養細胞などからエクソソームを精製・回収した後にペプチド付与などの修飾を施したり、エクソソームの供給元である細胞あるいは動植物等に遺伝子改変を施したりすることで、特定の機能をEVsに付与するもの、また特定の治療薬を内包することでドラッグデリバリーシステム(DDS)の担体として利用する改変型EVsがあり、今回の結果は、改変型エクソソームを将来、目指す上での重要な基盤データを得ることができた。

Report

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

    (9 results)

All 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Analysis of distribution, collection, and confirmation of capacity dependency of small extracellular vesicles toward a therapy for liver cirrhosis2023

    • Author(s)
      Takeda Nobutaka、Tsuchiya Atsunori、Mito Masaki、Natsui Kazuki、Natusi Yui、Koseki Yohei、Tomiyoshi Kei、Yamazaki Fusako、Yoshida Yuki、Abe Hiroyuki、Sano Masayuki、Kido Taketomo、Yoshioka Yusuke、Kikuta Junichi、Itoh Tohru、Nishimura Ken、Ishii Masaru、Ochiya Takahiro、Miyajima Atsushi、Terai Shuji
    • Journal Title

      Inflammation and Regeneration

      Volume: 43 Issue: 1 Pages: 48-48

    • DOI

      10.1186/s41232-023-00299-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Small extracellular vesicles and liver diseases: From diagnosis to therapy2022

    • Author(s)
      Tsuchiya Atsunori、Natsui Kazuki、Ishii Yui、Koseki Yohei、Takeda Nobutaka、Tomiyoshi Kei、Yamazaki Fusako、Yoshida Yuki、Terai Shuji
    • Journal Title

      World Journal of Hepatology

      Volume: 14 Issue: 7 Pages: 1307-1318

    • DOI

      10.4254/wjh.v14.i7.1307

    • Related Report
      2022 Research-status Report
  • [Journal Article] Basic points to consider regarding the preparation of extracellular vesicles and their clinical applications in Japan2022

    • Author(s)
      Tsuchiya Atsunori、Terai Shuji、Horiguchi Ikki、Homma Yasuhiro、Saito Atsuhiro、Nakamura Norimasa、Sato Yoji、Ochiya Takahiro、Kino-oka Masahiro
    • Journal Title

      Regenerative Therapy

      Volume: 21 Pages: 19-24

    • DOI

      10.1016/j.reth.2022.05.003

    • Related Report
      2022 Research-status Report
  • [Presentation] New normalへの提言-肝硬変に対する線維化改善を目指したトランスレーショナルリサーチ2023

    • Author(s)
      土屋淳紀、渡邉雄介、寺井崇二
    • Organizer
      JDDW
    • Related Report
      2023 Annual Research Report
  • [Presentation] 肝硬変に対する細胞治療、細胞外小胞(エクソソーム)治療、ペプチド治療の開発状況2023

    • Author(s)
      土屋淳紀、寺井崇二
    • Organizer
      日本再生医療学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝硬変に対してのデザイナー細胞外小胞(エクソソーム)治療の可能性2023

    • Author(s)
      土屋淳紀、寺井崇二
    • Organizer
      日本再生医療学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Therapies using mesenchymal stem cells and their small extracellular vesicle for liver cirrhosis2022

    • Author(s)
      Atsunori Tsuchiya, Shuji Terai
    • Organizer
      JDDW
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝硬変のマクロファージをターゲットとしたエクソソーム治療の可能性2022

    • Author(s)
      土屋淳紀、寺井崇二
    • Organizer
      消化器免疫学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 間葉系幹細胞由来細胞外小胞を用いた肝硬変治療法の開発(基礎研究から臨床応用へ)2022

    • Author(s)
      寺井崇二、土屋淳紀
    • Organizer
      日本細胞外小胞学会
    • Related Report
      2022 Research-status Report

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Published: 2022-07-05   Modified: 2025-01-30  

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