Engineered heart tissues formed with cardiac progenitors and differentiated cardiomyocytes exhibit similar physiologic properties at differentiation-matched timepoints

Abstract Congenital heart diseases, including single ventricle heart defects such as hypoplastic left and right heart syndromes, remain a leading cause of neonatal death and long-term morbidity. Regenerative medicine approaches hold great therapeutic promise for treating single ventricle disease, specifically through the use of human pluripotent stem cell-derived cardiomyocytes (iPSC-CM) to generate pulsatile conduits capable of growing and developing over time within the recipient. However, current strategies for rapidly fabricating large-scale engineered heart muscle to create such conduits face limitations, including the shear stress generated during most bioprinting processes along with harsh enzymatic treatments required for initial singularization of cells prior to bioprinting, which together can compromise cell viability and downstream tissue function. Here, we explored the use of derived cardiovascular progenitors (iPSC-CVP) as an alternative to fully differentiated cardiomyocytes as a potential cell source for future biomanufacturing efforts. We demonstrate that iPSC-CVP can be used to form functional engineered heart tissues with similar electrophysiological properties to tissues formed from fully differentiated iPSC-CM, while also being more amenable to enzymatic dissociation and mechanical manipulation. Our results suggest that iPSC-CVP may be an ideal cell population for future efforts in biofabrication of contractile structures such as engineered heart muscle and pulsatile conduits.