Construction of chamber-specific engineered cardiac tissues in vitro with human iPSC-derived cardiomyocytes and human foreskin fibroblasts

Human-induced pluripotent stem cell (hiPSC) technology and directed cardiac differentiation technology can provide a continuous supply of cells for disease modeling, drug screening, and cell therapy. However, two-dimensional (2D) cells often fail to faithfully reflect the physiological structure and function of the heart. Considering the contractile function is the most critical and easy-to-understand function of cardiomyocytes, the engineered cardiac tissues (ECT) with mechanical properties may serve as an appropriate three-dimensional (3D) platform for drug evaluation. At present, there are various methods to generate ECTs, some of which are quite costly. In the present study, we proposed that human foreskin fibroblast (HFF) cells, as a cost-effective and accessible cell source, can promote the compaction and remodeling of ECTs. The HFFs derived ECTs displayed stable structural and functional characteristics with a higher performance-to-price ratio. Moreover, both ECTs made from atrial and ventricular cardiomyocytes showed an excellent drug response, demonstrating that the ECT with HFFs as an easy and reliable platform for drug evaluation.