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Development of heart failure treatment with micro-cardiac tissues with vascular network

Research Project

Project/Area Number 16K09507
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKeio University

Principal Investigator

Fujita Jun  慶應義塾大学, 医学部(信濃町), 特任准教授 (10306706)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords心不全 / 多能性幹細胞 / 心筋細胞 / 微小心筋組織 / 血管構築 / iPS細胞 / ES細胞 / 再生医療 / 心筋球 / 溶存酸素 / 成熟化 / 血管新生 / 再生医学
Outline of Final Research Achievements

The optimal conditions for preparation of micro-cardiac tissues (MCT) were determined. Their maturity and the importance of the oxygen supply were confirmed. We established a massive two-dimensional culture method of human iPS cell-derived cardiomyocytes to obtain high-quality cardiomyocytes. MCT were transplanted to hearts of immunodeficient mice. The transplanted MCT were engrafted in large quantities even in the long term after transplantation, and vascular network was confirmed. MCT was transplanted to myocardial infarction models in immunodeficient rats, as well. A large number of transplanted MCT were engrafted, and their cardiac function significantly improved even in the long term after transplantation. The engrafted MCT expressed connexin 43 and did not induce any lethal arrhythmia. From these results, it has become clear that MCT based on high-quality human cardiomyocytes has vascular network, and safely and efficiently improves cardiac function in heart failure.

Academic Significance and Societal Importance of the Research Achievements

ヒトES細胞、iPS細胞由来の再生心筋細胞を用いた心不全治療は、ドナー不足で移植数が伸び悩む心臓移植の代替療法として期待されている。しかし、細胞治療の成功は移植細胞がレシピエントの心臓に長期間生着できるかどうかにかかっている。本研究成果より高品質な心筋細胞を基盤として構築された微小心筋組織は血管網を有し、レシピエントの血流から酸素と栄養が供給されることによって長期生着することが明らかになった。さらに、有意な致死性不整脈を惹起せずに心機能を改善することが確認された。この方法により、再生心筋細胞を用いた重症心不全治療の革新的成果が期待できることより学術的および社会的意義は極めて大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 5 results,  Invited: 8 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell-derived cardiomyocytes2019

    • Author(s)
      Tabei R, Kawaguchi S, Kanazawa H, Tohyama S, Hirano A, Handa N, Hishikawa S, Teratani T, Kunita S, Fukuda J, Mugishima Y, Suzuki T, Nakajima K, Seki T, Kishino Y, Okada M, Yamazaki M, Okamoto K, Shimizu H, Kobayashi E, Tabata Y, Fujita J, Fukuda K
    • Journal Title

      The Journal of heart and lung transplantation

      Volume: 38 Issue: 2 Pages: 203-214

    • DOI

      10.1016/j.healun.2018.11.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 臨床応用前夜となったヒトiPS細胞を用いた再生医療 ~心臓再生医療でみる産業化への歩み~2019

    • Author(s)
      神宿 元、藤田 淳、遠山 周吾、福田 恵一
    • Journal Title

      医工学治療

      Volume: in press

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 臨床応用前夜となったiPS細胞による心筋再生医療の今後の展開2018

    • Author(s)
      岸野 喜一、遠山周吾、藤田 淳、福田 恵一
    • Journal Title

      循環制御

      Volume: 39 Pages: 152-154

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 心筋再生とiPS細胞2018

    • Author(s)
      岡田 麻里奈、藤田 淳、福田 恵一
    • Journal Title

      臨床と研究

      Volume: 95 Pages: 649-652

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Efficient large-scale 2D culture system for human induced pluripotent stem cells and differentiated cardiomyocytes.2017

    • Author(s)
      Toyama S, Fujita J*, Fujita C, Yamaguchi M, Kanaami S, Ohno R, Sakamoto K, Kodama M, Kurokawa J, Kanazawa H, Seki T, Kishino Y, Okada M, Nakajima K, Tanosaki S, Someya S, Hirano A, Kawaguchi S, Kobayashi E, Fukuda K
    • Journal Title

      Stem Cell Rep

      Volume: 9 Issue: 5 Pages: 1406-1414

    • DOI

      10.1016/j.stemcr.2017.08.025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 心筋スフェロイド移植法を用いた心臓再生医療の開発2019

    • Author(s)
      藤田 淳
    • Organizer
      第19回 京大病院 iPS細胞・再生医学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regenerative therapy for heart failure with iPS-derived cardiac spheroid2018

    • Author(s)
      藤田 淳
    • Organizer
      Keio University International Symposium on Advanced Technologies for Mechano-biology and Regenerative Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 拡張型心筋症に対する再生心筋細胞移植療法2018

    • Author(s)
      藤田 淳
    • Organizer
      第22回日本心不全学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 心臓再生医療の実現に向けて2018

    • Author(s)
      藤田 淳
    • Organizer
      第39回日本炎症・再生医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた心臓再生医療の開発2018

    • Author(s)
      藤田 淳
    • Organizer
      3.Collaborative Evolution Laboratories Leading the acceleration of bioengineering: CELLab セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of a Massive Cardiac Spheroids Production and Transplantation System in Human Pluripotent Stem Cells2018

    • Author(s)
      Tohyama S, Fujita J, Kanazawa H, Tabei R, Kawaguchi S, Kobayashi E, Fukuda K.
    • Organizer
      The 16th annual scientific meeting of the International Society for Stem Cell Research (ISSCR).
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic Selection System for Large Numbers of Human iPSC-Derived Cardiomyocytes2018

    • Author(s)
      Tohyama S, Fujita J, Fujita C, Yamaguchi M, Ohno R, Fukuda K
    • Organizer
      Weinstein 2018 (Cardiovascular Developmental and Regeneration Conference)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic Selection System for Large Numbers of Human iPSC-Derived Cardiomyocytes2018

    • Author(s)
      Tohyama S, Fujita J, Fujita C, Yamaguchi M, Ohno R, Fukuda K
    • Organizer
      Keystone Symposia (Kyoto)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞を用いた心臓再生医療の開発2018

    • Author(s)
      藤田淳
    • Organizer
      第17回日本再生医療学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] iPS細胞を用いた再生心筋細胞移植による心不全治療法2017

    • Author(s)
      藤田淳
    • Organizer
      第21回心不全学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Development of a Transplant Injection Device for the Optimal Distribution and Retention of iPS Cell-Derived Cardiomyocytes.2017

    • Author(s)
      Tabei R, Kanazawa H, Fujita J, Tohyama S, Hirano A, Kawaguchi S, Nakajima K, Seki T, Kishino Y, Okada M, Shimizu H, Kobayashi E, Tabata Y, Fukuda K.
    • Organizer
      American Heart Association, Scientific Sessions 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞の代謝システム2017

    • Author(s)
      藤田淳
    • Organizer
      第9回泌尿器抗加齢医学研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] iPS由来心筋細胞を用いた重症心不全に対する心筋再生医療における 移植デバイスの開発2016

    • Author(s)
      田部井亮太、金澤英明、藤田淳、遠山周吾、平野暁教、川口新治、志水秀行、田畑泰彦、小林英司、福田恵一
    • Organizer
      第20回日本適応医学会学術集会
    • Place of Presentation
      東京コンベンションホール (東京都中央区)
    • Year and Date
      2016-12-16
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞培養装置及びその使用2017

    • Inventor(s)
      藤田淳、福田恵一、遠山周吾
    • Industrial Property Rights Holder
      藤田淳、福田恵一、遠山周吾
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-193600
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2022-12-28  

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