Project/Area Number |
20K20471
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Project/Area Number (Other) |
19H05563 (2019)
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Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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Allocation Type | Multi-year Fund (2020) Single-year Grants (2019) |
Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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Research Institution | The 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)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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Project Status |
Completed (Fiscal Year 2023)
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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)
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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。
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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.
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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。
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