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Trials to reconsitute stem cell system in the heart for cardiac regeneration

Research Project

Project/Area Number 20K20471
Project/Area Number (Other) 19H05563 (2019)
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund (2020)
Single-year Grants (2019)
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionThe University of Tokyo (2022-2023)
Kyoto University (2019-2021)

Principal Investigator

Yamashita Jun  東京大学, 医学部附属病院, 特任教授 (50335288)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2021: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2020: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords心筋前駆細胞 / 心臓再生 / iPS細胞 / 幹細胞 / 増殖 / 心筋幹細胞 / 心臓幹細胞 / 心臓前駆細胞
Outline of Research at the Start

本研究は心臓の「幹細胞システムそのものを再構築すること」により、永続的な心臓再生と若々しい心機能維持が実現可能な「新しい心臓」を作り出す画期的な新規心臓再生戦略を開発することを目的とする。研究代表者らが最近報告したヒト多能性幹細胞由来心筋特異的前駆細胞を元に、同細胞の幹細胞化と移植効果を小動物心不全モデルを用いて検討する。幹細胞システム構築による再生戦略は、他の臓器にも適用拡大可能であり、永続的再生と機能維持が可能な新たな臓器改変をもたらし、飛躍的な健康寿命の延伸につながる大きな潜在的ポテンシャルを有する。

Outline of Final Research Achievements

The principal investigators previously induced and identified "cardiomyocyte-fated progenitor cells (CFP cells)" from human iPS cells, which specifically differentiate into cardiomyocytes even after transplantation into the heart. In this study, we investigated culture conditions that allow CFP cells to proliferate while maintaining their cardiomyocyte differentiation potential and use them as cardiomyocyte-fated stem cells (CF-Stem cells). As a result, CFP cells were able to proliferate for up to 7 days. Upon transplantation of CFP cells into rat hearts, almost all (>95%) of the CFP cells differentiated into cardiomyocytes positive for cardiac troponin, and maturation at the cellular and tissue levels was observed 8 weeks after transplantation. Although complete stem cell transformation of CFP cells was challenging, the potential for efficient cardiac regenerative cell therapy based on CFP cells has expanded.

Academic Significance and Societal Importance of the Research Achievements

自己再生能がない心臓は再生医療の重要なターゲットである。本研究は幹細胞生物学を元に再生と機能維持が実現可能な「新しい心臓」を作り出す新規心臓再生戦略を開発することを目的とした。研究代表者らが誘導・同定した新しい心筋前駆細胞-1個の細胞から約7個の心筋細胞を生み出すことができる心筋前駆細胞―を用いることにより、従来よりも高効率な新たな心臓再生治療の可能性が広がった。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Annual Research Report
  • Research Products

    (22 results)

All 2024 2023 2022 2021 2020 2019 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 7 results) Remarks (1 results)

  • [Journal Article] The pathways of pluripotent stem cells to clinical applications.2024

    • Author(s)
      Jun K. Yamashita
    • Journal Title

      Inflamm Regen.

      Volume: 44 Issue: 1 Pages: 5-5

    • DOI

      10.1186/s41232-024-00317-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues2024

    • Author(s)
      Maurissen TL, Kawatou M, Lopez-Davila V, Minatoya K, Yamashita JK, Woltjen K.
    • Journal Title

      Sci Rep.

      Volume: 14 Issue: 1 Pages: 2586-2586

    • DOI

      10.1038/s41598-024-52871-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic potential of human induced pluripotent stem cell?derived cardiac tissue in an ischemic model with unloaded condition mimicking left ventricular assist device2023

    • Author(s)
      Heima Daisuke、Takeda Masafumi、Tabata Yasuhiko、Minatoya Kenji、Yamashita Jun K.、Masumoto Hidetoshi
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: in press Issue: 3 Pages: 01095-4

    • DOI

      10.1016/j.jtcvs.2023.11.019

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific induction and long-term maintenance of high purity ventricular cardiomyocytes from human induced pluripotent stem cells.2020

    • Author(s)
      Fukushima H, Yoshioka M, Kawatou M, Lopez-Davila V, Takeda M, Kanda Y, Sekino Y, Yoshida Y,Yamashita JK
    • Journal Title

      PLoS One

      Volume: 15 Issue: 11 Pages: 0241287-0241287

    • DOI

      10.1371/journal.pone.0241287

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 再生医療への幹細胞/ティッシュエンジニアリング融合技術の役割と新展開2024

    • Author(s)
      山下潤
    • Organizer
      日本再生医療学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 再生医療への幹細胞/ティッシュエンジニアリング融合技術の役割と新展開2023

    • Author(s)
      山下 潤
    • Organizer
      日本再生医療学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 血管内塞栓を形成しない安全な基材による新しい効率的心筋前駆細胞移植法の開発2023

    • Author(s)
      山下 潤
    • Organizer
      日本再生医療学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Cardiovascular regeneration with human iPS cell-derived heart tissue2022

    • Author(s)
      Jun K. Yamashita
    • Organizer
      Symposium on Medical Exchange of Shanghai University and the University of Tokyo
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ミニ3D心臓組織によるTdPの再現:適度な不均一性と3D構造による創発2021

    • Author(s)
      山下潤
    • Organizer
      第67回日本不整脈心電学会学術大会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 臨床応用に至ったiPS/ ES細胞研究の最前線2021

    • Author(s)
      山下潤
    • Organizer
      第42回日本炎症・再生医学会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞研究でいったい何ができるのか? -基礎から臨床、産業化へ-2021

    • Author(s)
      山下潤
    • Organizer
      日本医科大学大学院特別講義
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Keynote Lecture「再生」多能性幹細胞からの心血管細胞分化研究 -構成的アプローチによる Organoid, 再生医療、病態モデル-2021

    • Author(s)
      山下潤
    • Organizer
      CVMW2021心血管代謝週間 第29回日本血管生物医学会学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 多能性幹細胞由来3次元的構造形成と機能再現における間葉系細胞の意義2021

    • Author(s)
      山下潤
    • Organizer
      第7回日本筋学会学術総会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞を用いたヒト心筋細胞増殖機構の解析2021

    • Author(s)
      吉岡 美樹 , 山下 潤
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] iPS細胞由来内皮細胞の効率的な分化誘導及び安定的増殖法2020

    • Author(s)
      吉岡 美樹 , 山下 潤
    • Organizer
      第19回再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Stem cells meet tissue engineering -幹細胞生物学と組織工学による3D組織構築-2020

    • Author(s)
      山下 潤
    • Organizer
      第19回再生医療学会総会シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] 細胞から組織へ -多能性幹細胞由来心臓組織の作製とその治療応用-2020

    • Author(s)
      山下 潤
    • Organizer
      第19回再生医療学会総会シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒトiPS細胞由来心臓組織を用いた心臓再生及び病態モデル2020

    • Author(s)
      山下 潤
    • Organizer
      第41回日本炎症・再生医学会シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] iPS細胞で心臓を再生する2019

    • Author(s)
      山下 潤
    • Organizer
      奈良大宮ロータリークラブ 第1920回例会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた分化再生研究 ーStem cells meet chemical biology-2019

    • Author(s)
      山下 潤
    • Organizer
      早稲田大学先進理工学部講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた心血管分化再生研究2019

    • Author(s)
      山下 潤
    • Organizer
      Kyushu Vascular Biology & Medicine
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Remarks] 東京大学大学院医学系研究科

    • URL

      https://www.m.u-tokyo.ac.jp/

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2019-07-04   Modified: 2025-01-30  

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