Abstract 11425: Vascular Organ-Chips Made from Blood
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Introduction: 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. But these methods are difficult to adopt in labs and limit the power of organ-chips in making accurate physiological predictions. Hypothesis: In this study, we report Blood Outgrowth Endothelial Cells as a suitable alternative to primary and iPSC-derived endothelial cells. Through organ-chip and RNA sequencing, we further demonstrate that patient-blood derived BOECs are disease-specific and can differentiate sickle cell disease (SCD) patients. Methods: We isolate BOECs from healthy blood samples and compare their genotype, phenotype and organ-chip functional characteristics against commercially available and most commonly used HUVECs and iPSC-derived endothelial cells. To study patient-specificity, we isolate BOECs from two clinically distinct SCD patients and compare the presence of proinflammatory and endothelial activation pathways as predicted by RNA sequencing of autologous BOECs. Finally, we study the differences in thromboinflammation and endothelial activation between patient BOECs through vessel-chips. Results: Blood-derived endothelial cells exhibit the gold-standard hallmarks of typical endothelial cells. BOECs exhibit the classic endothelial cobblestone morphology in vitro and exhibit growth rates, migration abilities, de novo vessel formation, response to fluid shear and exogenous cytokine stimulation in a manner comparable to HUVECs and iECs. When isolated from SCD patients, BOECs exhibit an activated state as predicted by differential gene expression (DGE) and pathway analysis. Finally, real-time healthy whole blood perfusion through endothelialized vessel-chips with BOECs from more severe SCD patient yielded higher platelet adhesion compared to patient with mild severity. Conclusions: Blood-derived endothelial cells may be employed in preclinical research for developing more robust and personalized next-generation disease models.
