Synchronous beating between xenografted human cardiomyocytes and host zebrafish embryonic hearts

Injured human hearts are fibrotic, whereas zebrafish hearts functionally regenerate following myocardial injury. The unique regeneration niche microenvironment has been extensively studied in zebrafish hearts. However whether this can be extrapolated to humans remains unclear owing to significant species differences. We xenografted human induced pluripotent stem cell-derived cardiomyocytes (hiCMs) into the cardiac region of one-day post-fertilized zebrafish embryos and established a zebrafish xenograft model of hiCMs. This model can be used to explore the behavior of hiCMs transplanted into zebrafish hearts. Fluctuations in the fluorescence intensity of the genetically encoded calcium indicator protein GCaMP indicated that the donor hiCMs were beating. We analyzed the synchronization of the GCaMP + hiCMs transplanted into the zebrafish heart. We found synchronous beating between the host and 40 % of the zebrafish hearts with beating GCaMP-hiPSCs. Our chimeric heart model has the potential to bridge the regeneration capacity gap between zebrafish and humans and has proming future applications.