Spheroids of cardiomyocytes derived from human induced-pluripotent stem cells improve recovery from myocardial injury in mice

The microenvironment of native heart tissue may be better replicated when cardiomyocytes are cultured in three-dimensional clusters (i.e., spheroids) than in monolayers or as individual cells. Thus, we differentiated human, cardiac-lineage, induced-pluripotent stem cells into cardiomyocytes (hiPSC-CMs) and allowed them to form spheroids and spheroid fusions, which were characterized in vitro and evaluated in mice after experimentally induced myocardial infarction (MI). Synchronized contractions were observed within 24 hours of spheroid formation, and optical mapping studies confirmed the presence of both calcium transients and propagating action potentials. In spheroid fusions, the intraspheroid conduction velocity (CV) was 7.0{plus minus}3.8 cm/s on day 1-2 after formation, while the CV between spheroids increased significantly (p=0.003) from 0.8{plus minus}1.1 cm/s on day 1-2 to 3.3{plus minus}1.4 cm/s on day 7. For the murine MI model, five-spheroid fusions (200,000 hiPSC-CMs/spheroid) were embedded in...