Elucidation of the cardiac repair-mechanism by pluripotent stem cell-derived cardiomyocytes

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17554
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• 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, 助教 (70799064)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 多能性幹細胞 / 特性変化 / 心筋成熟化

Outline of Final Research Achievements

When human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively mature ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of mature ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

多能性幹細胞由来心筋細胞を用いた心筋再生療法は臨床試験が開始されたが、移植後の心室性不整脈出現が解決すべき課題として残されている。本研究で明らかになった生着心筋細胞の特性変化は、不整脈が移植1ヵ月後をピークとして徐々に減少するメカニズムの1つであると考えられた。今後、ペースメーカー細胞の割合を減らした場合や、成熟させた心筋を移植した場合に、不整脈の出現が減少するかを大動物を用いた実験で検証する必要がある。