Cardiac repair using autologous iPS cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19521
• 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: Shinshu University
• Principal Investigator: Shiba Yuji 信州大学, 学術研究院医学系, 教授 (70613503)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 心不全 / 再生医療 / iPS細胞

Outline of Final Research Achievements

This study compared autologous and allogeneic transplantation of cardiomyocytes derived from primate iPS cells in a chronic myocardial infarction model. Five lines of cynomolgus monkey iPS cells were created. These were differentiated cardiomyocytes, which were cryopreserved. Five monkeys were used for autologous transplantation and ten for allogeneic. In preclinical trials, monkeys underwent surgery to induce myocardial infarction. Twelve weeks later, they received autologous, allogeneic, or vehicle transplantation. Four weeks post-transplantation, the hearts were analyzed for graft survival, immune rejection, and tumor formation.Autologous transplants showed graft cardiomyocyte survival, while allogeneic transplants exhibited significant immune rejection. No tumors were detected in either group. This indicates autologous iPS cell-derived cardiomyocytes can survive without immunosuppressants, highlighting their potential for treating chronic myocardial infarction.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

自己細胞を用いた心臓再生は、ドナー不足だけでなく、免疫抑制剤の長期使用を解決するための理想的なストラテジーであるが、実現するためには、自家移植の免疫学的優位性の証明と慢性心不全に対する治療効果の検証が必要である。
本研究ではアカデミアにおいて、これらの課題を解決し、理論的に自己細胞を用いた心臓再生が可能であることを証明できた。研究成果をきっかけとして、産学官が一体となって、安価な培養試薬の開発、効率的な細胞製造プロトコールの確立、実効性の高い品質規制などの課題に取り組み、自己細胞を用いた再生医療の普及を目指す。