Next generation personalized blood vesselonchip: Mimicking patientspecific pathophysiology in sickle cell disease through bloodderived endothelial progenitors
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Advances in tissue engineering and organchip technology have accelerated in vitro research of the vascular system. Incorporating patientderived endothelial cells either through direct tissue biopsies or stem cell differentiation techniques further enhance the impact of organchips on precision medicine. However, these methods pose certain challenges and might be difficult to adopt in lab, thereby limiting the predictive power of organchips. Here we report the use of Blood Outgrowth Endothelial Cells (BOECs) directly isolated from patient blood as an alternative to primary and iPSCderived endothelial cells for organchip applications. BOECs exhibit the goldstandard endothelial hallmarks of the cobblestone morphology in vitro. When compared to primary HUVECs and iPSCderived endothelial cells, healthy BOECs reveal similar levels of growth rates, migration capabilities, de novo vessel formation, response to fluid shear stress and exogenous cytokine inflammation in vitro. To study patientspecificity, we derive BOECs from two sickle cell disease (SCD) patients with known differences in clinical severity of the disease. Through next generation RNA sequencing, differential gene expression (DGE) analysis and qRTPCR, we reveal that SCD patientderived BOECs are indeed activated and that the more severe SCD patient exhibited a greater magnitude of activation. This is further confirmed by realtime recalcified whole blood perfusion through endothelialized vesselchips. Bloodderived endothelial cells may be employed in preclinical research for developing more robust and personalized nextgeneration disease models that can ultimately enable clinicians in identifying individuals at high risk of stroke or cardiovascular complications.
