Feeder-Free Generation of Endocardial and Cardiac Valve Cells from Human Pluripotent Stem Cells

Valvular heart disease presents a significant health burden, yet advancements in valve biology and novel therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells. Importantly, we show that these endocardial cells are transcriptionally and phenotypically distinct from vascular endothelial cells and can be directed to undergo endothelial-to-mesenchymal transition (EndMT) to generate cardiac valve cell populations. Following this, we identified two distinct populations--one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs). Lastly, we confirmed the identities of our iPSC-derived cell populations and identified putative markers through transcriptomic analyses. By increasing the accessibility to these cell populations, we aim to accelerate discoveries for cardiac valve biology and disease.