Elucidation of mechanisms for maintaining automaticity by pacemaker cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08100
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Shinshu University
• Principal Investigator: Kadota Shin 信州大学, 学術研究院医学系, 講師 (70799064)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HCN4 / 自動能 / 心筋細胞 / 成熟化

Outline of Final Research Achievements

We differentiated cardiomyocytes from human induced pluripotent stem cells labeled with the HCN4 gene expression and produced mature cardiomyocytes using prolonged culture and maturation-promoting factors. When compared to cardiomyocytes cultured for 40 days, the expression of HCN4 decreased with the addition of prolonged culture or maturation-promoting factors. While cells cultured long-term with the addition of maturation-promoting factors exhibited the highest level of maturity, the expression of HCN4 did not decrease compared to each factor alone, indicating no synergistic effect between maturation-promoting factors and prolonged culture. In another experiment, cardiomyocytes cultured for an extended period showed improved engraftment, maturation, and angiogenesis post-transplantation, suggesting a contribution of CRYAB gene expression to these improvements.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

多能性幹細胞由来の心筋細胞の成熟過程においてHCN4発現の低下が認めたが、HCN4発現メカニズムの解明には更なる研究が必要である。一方で、成熟心筋細胞を移植した後に生着機能および血管新生能が増進することが示され、多能性幹細胞由来心筋細胞の再生医療応用における重要な進展となると考える。