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Bioinformatics approach to establish preconditioning method for beta cell replacement

Research Project

Project/Area Number 15K10033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionKyoto University

Principal Investigator

Anazawa Takayuki  京都大学, 医学研究科, 助教 (90566811)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords膵島移植 / 細胞移植 / 糖尿病 / 再生医療 / 免疫寛容 / 移植外科学
Outline of Final Research Achievements

Strategies to reduce the immunogenicity of pancreatic islets is essential for successful islet engraftment. We previously demonstrated that mitomycin C (MMC) pretreatment significantly prolonged graft survival. Fully understanding the biological process could result in the development of a protocol. The gene expression analysis identified downregulation of annotated functions associated with cellular movement and revealed significant downregulation of multiple genes encoding proinflammatory mediators with chemotactic activity. Validation studies revealed significantly decreased levels of IL-6, MCP-3, and MMP-2 in culture supernatants of MMC-treated islets. We also showed that MMC-treated islets secreted lower levels of chemoattractants that synergistically reduced the immunogenic potential of islets. The pretreatment of islets with MMC can reduce the immunogenic potential and prolong the survival of islet grafts by inducing the suppression of multiple leukocyte chemotactic factors.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Journal Article] β Cell Replacement Therapy: The Next 10 Years2018

    • Author(s)
      Schuetz Christian、Anazawa Takayuki、Cross Sarah E.、Labriola Leticia、Meier Raphael P.H.、Redfield Robert R.、Scholz Hanne、Stock Peter G.、Zammit Nathan W.
    • Journal Title

      Transplantation

      Volume: 102 Issue: 2 Pages: 215-229

    • DOI

      10.1097/tp.0000000000001937

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ex vivo Pretreatment of Islets with Mitomycin C2017

    • Author(s)
      Sato Naoya、Haga Junichiro、Anazawa Takayuki、Kenjo Akira、Kimura Takashi、Wada Ikuo、Mori Tsutomu、Marubashi Shigeru、Gotoh Mitsukazu
    • Journal Title

      Cell Transplantation

      Volume: 26 Issue: 8 Pages: 1392-1404

    • DOI

      10.1177/0963689717721233

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ex vivo pretreatment of islets with mitomycin C: Reduction in immunogenic potential of islets by suppressing secretion of multiple chemotactic factors2017

    • Author(s)
      Sato N, Anazawa T et al.
    • Journal Title

      Cell Transplantation

      Volume: In press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] A simple and promising strategy for pancreatic islet preconditioning to reduce immunogenicity and improve islet graft longevity2018

    • Author(s)
      Takayuki Anazawa, Kei Yamane, Seiichiro Tada, Kenta Inoguchi, Toshihiko Masui, Kazuyuki Nagai, Naoya Sato, Shoichiro Sumi, Hideaki Okajima, Shinji Uemoto
    • Organizer
      27th International Congress of The Transplantation Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A comparative analysis of the clinical outcome of islet transplantation using donors after cardiac death vs intensive insulin therapy in patients with type 1 diabetes with severe hypoglycaemia unawareness: a 10-year follow-up at a single centre2017

    • Author(s)
      Takayuki Anazawa, Hideaki Okajima, Yasuhiro Iwanaga, Toshihiko Masui, Seiichiro Tada, Kei Yamane,Kenta Inokuchi, Kyoichi Takaori, Yoshiya Kawaguchi, Shinji Uemoto
    • Organizer
      16th International Congress of International Pancreas and Islet Transplant Association
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵島移植の現状と今後の展開:膵島移植技術は日本で活かせるのか?2017

    • Author(s)
      穴澤貴行
    • Organizer
      第72回日本消化器外科学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵島移植の方向性:臨床経験からの成果と課題2017

    • Author(s)
      穴澤貴行、岡島英明、増井俊彦、伊藤孝司、多田誠一郎、山根 佳、井ノ口健太、海道利美、上本伸二
    • Organizer
      第53回日本移植学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵島移植が拓く近未来の組織・細胞治療2017

    • Author(s)
      穴澤貴行
    • Organizer
      第16回日本組織移植学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] A 10-year outcome of pancreatic islet transplantation2016

    • Author(s)
      Anazawa T, et al
    • Organizer
      IAP and JPS and AOPA 2016
    • Place of Presentation
      Sendai, Japan
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 次世代の細胞移植療法開発における探索的医療研究の役割:膵島移植からの成果報告2016

    • Author(s)
      穴澤貴行、他
    • Organizer
      第116回日本外科学会定期学術集会(ワークショップ)
    • Place of Presentation
      大阪
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Pancreatic islet culture induces tolerogenic effects as well as stimulates immune cell trafficking by regulating inflammatory cytokines2015

    • Author(s)
      Takayuki Anazawa, et al.
    • Organizer
      IPITA-IXA-CTS 2015 Joint Congress
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive gene analysis on ex-vivo Mitomycin-C treatment as a potential protocol for inducing unresponsiveness to islet engraftment: harmonized downregulation of multiple chemotaxis factors2015

    • Author(s)
      Naoya Sato, Takayuki Anazawa, et al.
    • Organizer
      IPITA-IXA-CTS 2015 Joint Congress
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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