Introduction: Human induced pluripotent stem cells (hiPSCs) hold enormous potential for cell-based therapy applications as they are capable of giving rise to unlimited number of terminally differentiated cell types for use in tissue engineering, drug development, and autologous cell therapy.Most of the cardiac 2D cell therapy studies exhibit poor survival of transplanted cells and diffuse distribution of cell grafts. This has prompted us to develop a scaffold-free 3D spheroid model from hiPSC-derived cardiomyocytes (hiPSC-CM's) to increase cell survival and improve cardiac function.
Methods: We developed and characterized 3D spheroid culture from hiPSC-CM's. Optical mapping was used to measure electrical properties of individual spheroids and fused spheroids in vitro. We evaluated spheroid transplantation and its potency for myocardial repair in the infarcted immunocompromised mice. Cardiac function was determined via echocardiography (Mice). Infarction size was assessed by bioluminescence and histology, and engraftment rate was assessed by histology.
Results: We observed few necrotic cells in spheroids generated from 3D spheroid culture of hiPSC-CM's. Both individual and fused spheroids derived from hiPSC-CM’s began generating calcium transients and beat synchronously in vitro. Comparing to those receiving cell injection, animals receiving spheroids displayed significantly improved cardiac function, evaluated by LV ejection fraction (EF) and fractional shortening (FS). Histological analysis showed significant engraftment of hiPSC-derived cardiac spheroids up to 4 weeks post transplantation.
Conclusions: Our study established the promising therapeutic potential of spheroids derived from hiPSC-differentiated CMs.