Comparative Analysis of Blood-Derived Endothelial Cells for Designing Next-Generation Personalized Organ-on-Chips

Background Organ-on-chip technology has accelerated in vitro preclinical research of the vascular system, and a key strength of this platform is its promise to impact personalized medicine by providing a primary human cell-culture environment where endothelial cells are directly biopsied from individual tissue or differentiated through stem cell biotechniques. However, these methods are difficult to adopt in laboratories, and often result in impurity and heterogeneity of cells. This limits the power of organ-chips in making accurate physiological predictions. In this study, we report the use of blood-derived endothelial cells as alternatives to primary and induced pluripotent stem cell-derived endothelial cells. Methods and Results Here, the genotype, phenotype, and organ-chip functional characteristics of blood-derived outgrowth endothelial cells were compared against commercially available and most used primary endothelial cells and induced pluripotent stem cell-derived endothelial cells. The methods include RNA-sequencing, as well as criterion standard assays of cell marker expression, growth kinetics, migration potential, and vasculogenesis. Finally, thromboinflammatory responses under shear using vessel-chips engineered with blood-derived endothelial cells were assessed. Blood-derived endothelial cells exhibit the criterion standard hallmarks of typical endothelial cells. There are differences in gene expression profiles between different sources of endothelial cells, but blood-derived cells are relatively closer to primary cells than induced pluripotent stem cell-derived. Furthermore, blood-derived endothelial cells are much easier to obtain from individuals and yet, they serve as an equally effective cell source for functional studies and organ-chips compared with primary cells or induced pluripotent stem cell-derived cells. Conclusions Blood-derived endothelial cells may be used in preclinical research for developing more robust and personalized next-generation disease models using organ-on-chips.