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Development of immune tolerance method for clinical application of allogeneic iPS cells

Research Project

Project/Area Number 26293311
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionOsaka University

Principal Investigator

Miyagawa Shigeru  大阪大学, 医学(系)研究科(研究院), 特任教授(常勤) (70544237)

Co-Investigator(Kenkyū-buntansha) 戸田 宏一  大阪大学, 医学(系)研究科(研究院), 准教授 (40379235)
福嶌 五月  大阪大学, 医学(系)研究科(研究院), 助教 (80596867)
今西 悠基子  大阪大学, 医学(系)研究科(研究院), 特任研究員 (10707582)
川村 匡  大阪大学, 医学(系)研究科(研究院), 助教 (70583011)
秦 広樹  大阪大学, 医学(系)研究科(研究院), 助教 (80638198)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsiPS細胞 / iPS細胞由来心筋細胞 / 他家移植 / 免疫寛容 / MHC適合移植 / MSC併用移植 / 自然免疫 / 免疫抑制剤 / 免疫拒絶 / MHC / アロジェネイック / 心筋細胞
Outline of Final Research Achievements

The immune response against allogeneic cells is imperative issue in regenerative therapy using iPS cells. In MHC-matching transplantation of allogeneic iPS derived cardiomyocytes, infiltrating immune cells were less observed and transplanted cells were much survived compared with non-matching transplantation. The simultaneous transplanted MSCs showed the immune tolerance in allogeneic iPS derived cardiomyocytes transplantation without immunosupressants. In addition, we revealed the mechanism of innate immune response against iPS derived cardiomyocytes, leading to supression of innate and asociated acquired immune responce. Thus, the immunosupressants could be stopped or reduced in allogeneic iPS derived cardiomyocytes transplantation by using these methods. The immune responce could be evaluated using TSPO-PET, leading to exact adjustment of immunosupressants.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (18 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates.2016

    • Author(s)
      河村 拓史
    • Journal Title

      Stem Cell Reports

      Volume: 6 (3) Issue: 3 Pages: 312-320

    • DOI

      10.1016/j.stemcr.2016.01.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart.2016

    • Author(s)
      Miyagawa S, Fukushima S, Imanishi Y, Kawamura T, Mochizuki-Oda N, Masuda S, Sawa Y.
    • Journal Title

      Current Gene Therapy

      Volume: 16 Pages: 5-13

    • Related Report
      2015 Annual Research Report
    • Open Access / Acknowledgement Compliant
  • [Journal Article] Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.2016

    • Author(s)
      Kawamura A, Miyagawa S, Fukushima S, Kawamura T, Kashiyama N, Ito E, Watabe T, Masuda S, Toda K, Hatazawa J, Morii E, Sawa Y.
    • Journal Title

      Scientific Reports

      Volume: 29 Issue: 1 Pages: 22130-22130

    • DOI

      10.1038/srep19464

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural Changes in N-Glycans on Induced Pluripotent Stem Cells Differentiating Toward Cardiomyocytes.2015

    • Author(s)
      Kawamura T, Miyagawa S, Fukushima S, Kashiyama N, Kawamura A, Ito E, Saito A, Maeda A, Eguchi H, Toda K, Miyagawa S, Okuyama H, Sawa Y.
    • Journal Title

      Stem Cells Transl Med

      Volume: 4 Issue: 11 Pages: 1258-1264

    • DOI

      10.5966/sctm.2015-0029

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 再生医学を用いた重症心不全に対する挑戦2015

    • Author(s)
      宮川繁
    • Organizer
      第53回日本人工臓器学会
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Preventing Tumor Formation Following iPS Cell-Derived Cardiomyocytes Transplantation Therapy by Carbohydrate Vaccine Therapy Targeting Undifferentiated iPS Cell-Specific Antigen2015

    • Author(s)
      Kawamura T, Miyagawa S, Fukushima S, Kawamura A, Kashiyama N, Sawa Y
    • Organizer
      AHA2015 (American Heart Association Scientific Sessions)
    • Place of Presentation
      Orlando. USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of PET imaging to visualize activated macrophages in immune rejection of allogeneic iPS cell derived Cardiomyocytes in mice2015

    • Author(s)
      Kashiyama N, Miyagawa S, Fukushima S, Kawamura T, Yoshida S, Sawa Y
    • Organizer
      AHA2015 (American Heart Association Scientific Sessions)
    • Place of Presentation
      Orlando. USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immunogenic Verification of MHC-homo iPS Cell-derived Cardiomyocytes transplantation to an MHC-matched Non-human Primate Ischemic Cardiomyopathy model: Pre-Clinical Study for Allogeneic Therapy using iPS cells2015

    • Author(s)
      Kashiyama N, Miyagawa S, Fukushima S, Kawamura T, Yoshida S, Sawa Y
    • Organizer
      AHA2015 (American Heart Association Scientific Sessions)
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 重症心不全に対するiPS細胞由来心筋細胞シート治療の現状と展望2015

    • Author(s)
      宮川繁
    • Organizer
      第68回日本胸部外科学会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] PET imaging to visualize activated macrophages for detection of immune rejection in allotransplantation of iPS cell-derived cardiomyocytes in mice.2015

    • Author(s)
      樫山紀幸
    • Organizer
      第79回日本循環器学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Translational Research of iPS Cell Sheet-based Myocardial Regeneration Therapy2015

    • Author(s)
      宮川繁
    • Organizer
      第79回日本循環器学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Preventing allogeneic immune rejection by transplanting MHC-homo induced pluripotent stem cell-derived cardiomyocytes to an MHC-matched non-human primate2015

    • Author(s)
      河村拓史
    • Organizer
      第79回日本循環器学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞移植による心筋再生療法の開発と推進2015

    • Author(s)
      福嶌五月
    • Organizer
      第115回日本外科学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] iPS 細胞由来心筋細胞における糖鎖構造の解析とその意義2015

    • Author(s)
      河村拓史
    • Organizer
      第115回日本外科学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] MHCホモカニクイザルiPS細胞を用いたMHC一致移植の有用性の検討2015

    • Author(s)
      河村卓史、宮川繁、福嶌五月、齋藤充弘、前田晃、樫山紀幸、河村愛、吉田昇平、椎名隆、宮川周士、澤芳樹
    • Organizer
      第14回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] PET画像を用いたマウスiPS細胞由来心筋細胞の同種異系移植における免疫拒絶反応の評価2015

    • Author(s)
      樫山紀幸、宮川繁、仲村輝也、増田茂夫、吉川泰司、福嶌五月、齋藤充弘、斎藤俊介、吉岡大輔、斎藤哲也、河村拓史、河村愛、吉田昇平、上野孝義、戸田宏一、倉谷徹、澤芳樹
    • Organizer
      第14回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] カニクイザル用いたMHC ホモiPS 細胞由来心筋細胞移植の有用性の検討2015

    • Author(s)
      河村拓史、宮川繁、福嶌五月、齋藤充弘、前田晃、樫山紀幸、河村愛、吉田昇平、椎名隆、宮川周士、澤芳樹
    • Organizer
      第45回日本心臓血管外科学会
    • Place of Presentation
      京都
    • Year and Date
      2015-02-16 – 2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Preventing Allogeneic Immune Rejection by Transplanting MHC-homo Induced Pluripotent Stem Cell-derived Cardiomyocytes to an MHC-matched non-Human Primate2014

    • Author(s)
      Kawamura T, Miyagawa Shigeru, Fukushima S, Masuda S, Kashiyama N, Kawamura A, Ito E, Maeda A, Toda K, Miyagawa Shuji, Sawa Y.
    • Organizer
      AHA(American Heart Association)
    • Place of Presentation
      Chicago (USA)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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