Abstract
Regeneration therapy using derivatives of induced pluripotent stem cells(iPSCs)is a promising treatment for advanced cardiac failure. We herein document our studies for allogeneic transplantation therapy using iPSCs-derived cardiac myocytes(CMs), which were prepared as a scaffold-free cell-sheet form, for treating chronic cardiac failure in a large animal model. Cardiomyogenic differentiation was induced in iPSCs of human origin in vitro, showing that more than 80% of the cells were positive for cardiac specific markers. Scaffold-free cell-sheets of the iPSC-CMs, which were prepared by thermoresponsive culture dish, were then transplanted into the cardiac surfac e of the immune-suppressed pigs which were subjected to myocardial infarction 4 weeks prior to the treatment.As a result, global and regional cardiac function was significantly improved until 8 weeks after the treatment, as assessed by echocardiography and multi-slice CT scanning, without generating arrhythmia or tumor. The transplanted cells expressing cardiacspecific contractile proteins remained in the heart for 8 weeks.In conclusion, transplantation of the iPSC-CM cell-sheets into the pig chronic myocardial infarction model was feasible, safe and effective. Although pre-clinical proof-of-concept established, this treatment needs to be developed by further basic studies to ensure safety and enhance therapeutic efficacy to launch clinical study.
