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

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K20471
• Project/Area Number (Other): 19H05563 (2019)
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund (2020); Single-year Grants (2019)
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• 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)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 心筋前駆細胞 / 心臓再生 / iPS細胞 / 幹細胞

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.

Free Research Field

幹細胞生物学・循環器内科学

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。