1. Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques
- Author
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Lin, Yongshun, Sato, Noriko, Hong, Sogun, Nakamura, Kenta, Ferrante, Elisa A., Yu, Zu Xi, Chen, Marcus Y., Nakamura, Daisy S., Yang, Xiulan, Clevenger, Randall R., Hunt, Timothy J., Taylor, Joni L., Jeffries, Kenneth R., Keeran, Karen J., Neidig, Lauren E., Mehta, Atul, Schwartzbeck, Robin, Yu, Shiqin Judy, Kelly, Conor, Navarengom, Keron, Takeda, Kazuyo, Adler, Stephen S., Choyke, Peter L., Zou, Jizhong, Murry, Charles E., Boehm, Manfred, and Dunbar, Cynthia E.
- Abstract
Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivomaturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.
- Published
- 2024
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