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Development of novel anti-inflammatory therapy using mesenchymal stem cells

Research Project

Project/Area Number 18K07903
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionNiigata University

Principal Investigator

Tsuchiya Atsunori  新潟大学, 医歯学総合病院, 講師 (70464005)

Co-Investigator(Kenkyū-buntansha) 寺井 崇二  新潟大学, 医歯学系, 教授 (00332809)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords急性肝障害 / 間葉系幹細胞 / エクソソーム / miRNA
Outline of Final Research Achievements

We tried to develop mouse acute liver injury model using anti-Fas antibody, carbon tetrachloride (CCl4), CCl4 + lipopolysaccharide, acetaminophen and D-Galactosamine, and found that CCl4 induced acute liver injury model was most stable model for our analysis. Using this model, we tried to inject mesenchymal stem cells (MSCs) or their exosomes by three different ways around the time of acute liver damage; 1) pre-injection, 2) simultaneous injection, 3) post-injection. Our analysis showed that pre-injection of MSCs was most effective for acute liver injury. However, in clinical setting, pre-treatment of MSCs is very difficult, thus we concluded that MSC therapy is more appropriate for chronic liver injury model than acute liver injury model.

Academic Significance and Societal Importance of the Research Achievements

現在、慢性肝障害である肝硬変に対して、間葉系幹細胞やマクロファージなど様々な細胞治療や細胞を用いないセルフリー治療が日本、そして世界で開発されてきている一方、急性肝障害に対して、これらの細胞が、効果があるのかの検証はまだ十分とは言えない。急性肝障害に関しては、ステロイドをはじめとした治療があるものの、間葉系幹細胞治療の効果を検証すること、そして効果があるのであればその原因物質や機序を明らかにすることは有意義で有り、本研究を行うこととした。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019

All Journal Article (11 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (9 results)

  • [Journal Article] Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis2021

    • Author(s)
      Takeuchi S, Tsuchiya A, Iwasawa T、Nojiri S、Watanabe T、Ogawa M、Yoshida T、Fujiki K、Koui Y、Kido T、Yoshioka Y、Fujita M、Kikuta J、Itoh T、Takamura M、Shirahige K、Ishii M、Ochiya T、Miyajima A、Terai S
    • Journal Title

      npj Regenerative Medicine

      Volume: 6 Issue: 1

    • DOI

      10.1038/s41536-021-00132-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future2021

    • Author(s)
      Watanabe Yusuke、Tsuchiya Atsunori、Terai Shuji
    • Journal Title

      Clinical and Molecular Hepatology

      Volume: 27 Issue: 1 Pages: 70-80

    • DOI

      10.3350/cmh.2020.0194

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases2020

    • Author(s)
      Tsuchiya Atsunori、Takeuchi Suguru、Iwasawa Takahiro、Kumagai Masaru、Sato Takeki、Motegi Satoko、Ishii Yui、Koseki Youhei、Tomiyoshi Kei、Natsui Kazuki、Takeda Nobutaka、Yoshida Yuki、Yamazaki Fusako、Kojima Yuichi、Watanabe Yusuke、Kimura Naruhiro、Tominaga Kentaro、Kamimura Hiroteru、Takamura Masaaki、Terai Shuji
    • Journal Title

      Inflammation and Regeneration

      Volume: 40 Issue: 1

    • DOI

      10.1186/s41232-020-00121-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles2020

    • Author(s)
      Watanabe Takayuki、Tsuchiya Atsunori、Takeuchi Suguru、Nojiri Shunsuke、Yoshida Tomoaki、Ogawa Masahiro、Itoh Michiko、Takamura Masaaki、Suganami Takayoshi、Ogawa Yoshihiro、Terai Shuji
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 252-261

    • DOI

      10.1016/j.reth.2020.03.012

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptomic Dissection of Hepatocyte Heterogeneity: Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics2020

    • Author(s)
      Katsuda Takeshi、Hosaka Kazunori、Matsuzaki Juntaro、Usuba Wataru、Prieto-Vila Marta、Yamaguchi Tomoko、Tsuchiya Atsunori、Terai Shuji、Ochiya Takahiro
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 9 Issue: 1 Pages: 161-183

    • DOI

      10.1016/j.jcmgh.2019.08.011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions2019

    • Author(s)
      Kojima Yuichi、Tsuchiya Atsunori、Ogawa Masahiro、Nojiri Shunsuke、Takeuchi Suguru、Watanabe Takayuki、Nakajima Kenji、Hara Yukio、Yamashita Junji、Kikuta Junichi、Takamura Masaaki、Ishii Masaru、Terai Shuji
    • Journal Title

      Regenerative Therapy

      Volume: 11 Pages: 269-281

    • DOI

      10.1016/j.reth.2019.08.005

    • Related Report
      2019 Research-status Report
  • [Journal Article] Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration2019

    • Author(s)
      Tsuchiya Atsunori、Takeuchi Suguru、Watanabe Takayuki、Yoshida Tomoaki、Nojiri Shunsuke、Ogawa Masahiro、Terai Shuji
    • Journal Title

      Inflammation and Regeneration

      Volume: 39 Issue: 1

    • DOI

      10.1186/s41232-019-0107-z

    • Related Report
      2019 Research-status Report
  • [Journal Article] Efficacy of gelatin hydrogels incorporating triamcinolone acetonide for2019

    • Author(s)
      Nao Nakajima, Satoru Hashimoto, Hiroki Sato, Kazuya Takahashi, Takuro Nagoya, Kenya Kamimura, Atsunori Tsuchiya, Junji Yokoyama, Yuichi Sato, Hanako Wakatsuki, Masayuki Miyata, Yusuke Akashi, Ryusuke Tanaka, Ken Matsuda, Yasuhiko Tabata, Shuji Terai
    • Journal Title

      Regenerative Therapy

      Volume: 11 Pages: 41-46

    • DOI

      10.1016/j.reth.2019.04.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver stem cells: Plasticity of the liver epithelium2019

    • Author(s)
      Tsuchiya Atsunori、Lu Wei-Yu
    • Journal Title

      World Journal of Gastroenterology

      Volume: 25 Issue: 9 Pages: 1037-1049

    • DOI

      10.3748/wjg.v25.i9.1037

    • Related Report
      2019 Research-status Report
  • [Journal Article] Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells2019

    • Author(s)
      Kawata Yuzo、Tsuchiya Atsunori、Seino Satoshi、Watanabe Yusuke、Kojima Yuichi、Ikarashi Shunzo、Tominaga Kentaro、Yokoyama Junji、Yamagiwa Satoshi、Terai Shuji
    • Journal Title

      Cell and Tissue Research

      Volume: 376 Issue: 2 Pages: 257-271

    • DOI

      10.1007/s00441-018-02981-w

    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Journal Article] Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice2019

    • Author(s)
      Watanabe Yusuke、Tsuchiya Atsunori、Seino Satoshi、Kawata Yuzo、Kojima Yuichi、Ikarashi Shunzo、Starkey Lewis Philip J.、Lu Wei-Yu、Kikuta Junichi、Kawai Hirokazu、Yamagiwa Satoshi、Forbes Stuart J.、Ishii Masaru、Terai Shuji
    • Journal Title

      STEM CELLS Translational Medicine

      Volume: 8 Issue: 3 Pages: 271-284

    • DOI

      10.1002/sctm.18-0105

    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] 肝硬変に対するExosome治療2021

    • Author(s)
      寺井崇二,土屋淳紀
    • Organizer
      日本再生医療学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 間葉系幹細胞のエクソソームによる肝線維化改善抗炎症性マクロファージ誘導法の開発2020

    • Author(s)
      竹内卓、土屋淳紀、寺井崇二
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 間葉系幹細胞の治療効果メカニズム検証に基づく肝硬変に対するより効果的な治療法開発2020

    • Author(s)
      土屋淳紀、高村昌昭、寺井崇二
    • Organizer
      JDDW
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝硬変に対する間葉系幹細胞由来エクソソーム療法の開発に向けて2020

    • Author(s)
      土屋淳紀、竹内卓、寺井崇二
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] IFN-γ刺激下間葉系幹細胞由来エクソソームの肝線維化改善における効果・メカニズムの検証2020

    • Author(s)
      土屋淳紀, 竹内卓, 寺井崇二
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 消化器疾患での間葉系幹細胞を用いた治療法開発2019

    • Author(s)
      土屋淳紀、高村昌昭、寺井崇二
    • Organizer
      JDDW2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 間葉系幹細胞を指揮細胞として用いた肝硬変に対する再生医療の治療戦略2019

    • Author(s)
      寺井崇二、土屋淳紀、竹内卓
    • Organizer
      JDDW2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝硬変に対する間葉系幹細胞由来のエクソソーム療法の開発に向けて2019

    • Author(s)
      土屋淳紀、竹内卓、寺井崇二
    • Organizer
      日本肝臓学会西部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 消化器疾患での間葉系幹細胞を用いた再生医療の治療戦略2019

    • Author(s)
      土屋淳紀、小川雅裕、野尻俊介、渡邉貴之、竹内卓、小島雄一、川田雄三、寺井崇二
    • Organizer
      日本再生医療学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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