Elucidation of embryological maturation switch of cardiomyocytes and application to human iPS cell-derived cardiomyocytes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kansai Medical University
• Principal Investigator: HATTORI Fumiyuki 関西医科大学, 医学部, 教授 (50398624)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒトiPS細胞 / 心筋 / 成熟

Outline of Final Research Achievements

The low maturity of human iPS cell-derived cardiomyocytes is a practical obstacle. The representatives gained new insights that switch on cardiomyocyte maturation at specific stages of development. In this study, we attempted to clarify the components of the cardiomyocyte maturation switch. The cardiomyocytes and the non-cardiomyocytes were sorted and purified from each heart before and after the developmental switch-period, and comprehensive gene expression analyses were performed. We obtained the original immature and maturation markers. Furthermore, when the changes in gene expression were measured in cardiomyocytes to which the newly discovered myocardial maturation switch candidate factor group was added alone, some of them suggested the effect of increasing maturity.

Free Research Field

創薬、再生医療

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞から分化誘導した心筋細胞の成熟性が低いという事実は、これらを医療や創薬に応用するための大きな障害である。そのため、これを改善することは、医療の向上や創薬の効率化に繋がる。また、ヒトの発生において心筋細胞が分化し、その後成熟して行く過程に、どのような刺激や環境が重要であるのかを明らかにすることは、発生学的な意義がある。従来知識では、継続的に心筋細胞をトレーニングするような刺激が重要とされてきたが、報告者は、発生期における一過性の刺激が成熟化スイッチのような役割を担っていることを示唆し、この一端を解明した。