Dual function of hPSC-derived pericyte-like cells in vascularization and fibrosis-related cardiac tissue remodeling in vitro

In the heart, cardiomyocytes (CMs) are coupled to capillary endothelial cells (EC), mural cells (e.g. pericytes) and fibroblasts (Fb) promoting structural and electrophysiological tissue maturation as well as vascular network formation. Here, an in vitro model is shown for the investigation of the role of ECs, cardiac pericyte-like cells (PC) and different Fb sources in hPSC-derived bioartificial cardiac tissue (BCT) formation and function. The hPSC-based CMs, ECs, and PCs were differentiated, purified, and characterized for cell-type specific marker expression and function. Differentiated hPSC-PCs were used with hPSC-ECs to generate BCTs and to address their effect on tissue morphology and electromechanical parameters compared to control tissues containing primary dermal or cardiac Fbs. The transcriptome of three bioartificial cardiac tissue (BCT) groups with hPSC-derived cardiomyocytes (CM), hPSC-derived endothelial cells (EC) and different fibroblast-like cell types was compared to the differentiated CM source and adult human ventricle. The fibroblast-like cell types included human foreskin fbroblasts (group: CM+hFF+EC), human cardiac fibroblasts (group: CM+hCF+EC), and hPSC-derived cardiac pericyte-like cells (group: CM+PC+EC).