The next generation of endothelial differentiation: Tissue-specific ECs

Endothelial cells (ECs) sense and respond to fluid flow and regulate immune cell trafficking in all organs. Despite sharing the same mesodermal origin, ECs exhibit heterogeneous tissue-specific characteristics. Human pluripotent stem cells (hPSCs) can potentially be harnessed to capture this heterogeneity and further elucidate endothelium behavior to satisfy the need for increased accuracy and breadth of disease models and therapeutics. Here, we review current strategies for hPSC differentiation to blood vascular ECs and their maturation into continuous, fenestrated, and sinusoidal tissues. We then discuss the contribution of hPSC-derived ECs to recent advances in organoid development and organ-on-chip approaches. Human pluripotent stem cells (hPSCs) can be harnessed to capture the heterogeneous tissue-specific characteristics of endothelial cells (ECs) toward disease models and therapeutics. This review focuses on hPSC-EC derivation and maturation into continuous, fenestrated, and sinusoidal tissues and the contribution of hPSC-ECs to recent advances in organoid development and organ-on-chip approaches.