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

Abstract

SummaryValvular 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.

Advances in 3D Bioprinted Cardiac Tissue Using Stem Cell-Derived Cardiomyocytes

“… 17-20 Further, protocols for the generation of endocardial and valvular interstitial cells have only recently been established. 21 , 22 Importantly, these stem cell-derived cardiac cell types often exhibit fetal-like phenotypes, making maturation toward adult-like phenotypes an ongoing challenge to achieve improved function.…”

Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

“…One of the major avenues is for cardiac cells to be derived by differentiating human-induced pluripotent stem cells (iPSCs) or embryonic stem cells to cardiac lineages using signaling or environmental cues. Examples range from 2-dimensional cultures of cardiomyocytes, 98 epicardial cells, 99 and endocardial cells 100 to self-organizing organoid models with complex 3-dimensional structures. 101 Clinical implementation of stem cell-based technologies applied to the heart includes the recent development of 3-dimensional cardiac microtissues engineered from iPSCs harboring human mutations, allowing for rapid testing of potential therapeutics for correction of genetic defects and promotion of cardiac regeneration.…”