The transplantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a promising strategy to repair damaged myocardium. However, it often causes arrhythmogenic automaticity because of the poor electrical integration of transplanted cells with the neighboring cardiomyocytes. hiPSC-CMs also exhibit disorganized sarcomeres. In a recent study published in Science, Aoyama et al. use flexible mesh nanoelectronics to map the electrical activity of hiPSC-CMs transplanted into rat hearts in real time and show that the co-injection of hiPSC-CMs with self-assembling peptides such as RADA16 improved the maturation of cardiomyocytes and graft vascularization and reduced the arrhythmogenic automaticity in rat hearts.
RADA16 is a clinically approved hemostatic agent that can control bleeding during surgical procedures and wound healing, and it has the potential to improve cellular retention, organization and vascularization in tissue-engineered applications. Its administration to hiPSC-CMs promoted the acquisition of an adult-like transcriptomic profile. The co-injection of hiPSC-CMs and RADA16 into healthy rat hearts resulted in comparable engraftment but improved the graft vascularization and its interaction with the host blood vessels compared with injection of hiPSC-CMs alone. RADA16 promoted the maturation of sarcomeric isoforms within the first 7 days of cell transplantation, improved the organization of sarcomeres, and increased sarcomere length by 3 months after cell transplantation. By contrast, hiPSC-CMs transplanted alone still showed disorganized sarcomeres at the same time point. Flexible mesh nanoelectronics with a high-density microelectrode array recorded the electrical signals from the transplanted hiPSC-CMs, and the addition of RADA16 was shown to reduce the arrhythmogenic automaticity compared with injection of hiPSC-CMs alone. Further studies are necessary to test whether RADA16 can produce similar effects in damaged myocardial hearts.
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