Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells

Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-derived vascular cells self-organized to form stable microvascular networks reproducibly, in which the vessels were lumenized and functional, responding as expected to vasoactive stimulation. Vascular organization and intracellular Ca2+ release kinetics in VSMCs could be quantified using automated image analysis based on open-source software CellProfiler and ImageJ on widefield or confocal images, setting the stage for use of the platform to study vascular (patho)physiology and therapy.

Automated summary

The study developed a 3D vessel-on-chip model based on human induced pluripotent stem cells to recapitulate the crosstalk between endothelial cells and pericytes or vascular smooth muscle cells, enabling the study of vascular (patho)physiology and therapy. The hiPSC-derived vascular cells organized into stable microvascular networks within a fibrin hydrogel microenvironment and responded to vasoactive stimulation, demonstrating the model's potential for quantifying vascular organization and intracellular Ca2+ release kinetics.