Human Pluripotent Stem Cell-Derived Endothelial Cells in Disease Modeling and Drug Screening

Abstract

Endothelial dysfunction plays a critical role in the pathophysiology of numerous cardiovascular diseases, the leading cause of mortality globally. Accurate endothelial models are essential for disease modeling, understanding mechanisms of disease development, and drug screening. Animal models, though informative, often fail to replicate human disease conditions, as well as ethical considerations advocate for reducing animal experimentation in drug research. Human primary endothelial cells offer mature endothelial characteristics but are limited by availability, complicating reproducibility. Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) emerge as a promising alternative, providing an unlimited cell source. This study presents multiple useful methods to evaluate the phenotypic and functional properties of hiPSC-ECs. Immunohistochemistry and fluorescence-activated cell sorting (FACS) validated endothelial characteristics, morphology, texture, and marker presence, ensuring differentiation efficacy and cell culture viability. Functional assays, including wound healing and 3D spheroid-based angiogenesis, demonstrated that hiPSC-ECs mimic native endothelial cells. High-content screening approaches analyzed the endothelial phenotype, highlighting the potential of hiPSC-ECs in cardiovascular disease research and drug development.

Keywords: 3D cell culture; Artery; Endothelial cells; Endothelial differentiation; Functional test; High-content screening; Vascular disease model; hiPSC.