Evaluation of Post-Transplant Arrhythmia in Human iPSC-Derived Purified Ventricular Cardiomyocytes

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22626
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Keio University
• Principal Investigator: Tohyama Shugo 慶應義塾大学, 医学部(信濃町), 講師 (90528192)
• Co-Investigator(Kenkyū-buntansha): 柴 祐司 信州大学, 学術研究院医学系, 教授 (70613503)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: ヒトiPS細胞 / 心筋細胞 / サル / 催不整脈作用 / 再生医療

Outline of Final Research Achievements

Since human iPSCs can differentiate into various types of cells including cardiomyocytes, they are expected to be applied to regenerative medicine. However, to realize cardiac regenerative medicine, there is a risk of post-transplant arrhythmia. Therefore, we prepared purified ventricular cardiomyocytes from clinical-grade HLA homozygous human iPSCs by our developed clinical-grade culture system. Then, after production of cardiac spheroids, they were transplanted into cynomolgus monkey myocardial infarction models under immunosuppressive drug administration, and post-transplant arrhythmia and cardiac function were evaluated. As a result, we observed long-term engraftment of cardiac tissue and demonstrated that cardiac function was significantly improved and the risk of ventricular tachycardia was extremely low. Therefore, the transplanted purified ventricular cardiomyocytes were suitable for safer transplantation.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

本研究において、臨床用iPS細胞を用いて臨床グレードの純化心筋細胞および微小心筋組織球を大量に作製し、カニクイザルに移植を行い、長期生着を達成しながら、心機能の改善および催不整脈作用の評価ができたことは非常に大きな意義があると考えられる。また、我々のシステムで作製したヒトiPS細胞由来心筋組織球を移植した際には催不整脈作用が既存の報告に比べて極めて少ないことも特筆すべきである。今後は、どのような特性を持つ心筋細胞を移植した場合に催不整脈作用を有するのかに関しても解明していく必要があると考えている。