Endothelialized Microchannels as In Vitro Model of Small Vessels

Orateur : Daria TSVIRKUN (Moscow State University, Russia)

Microfluidic technology highly developed in physics is now widely used to create tools for cell biology. A variety of bioassays and investigations can be carried on in microfluidic systems where living cells can be cultured : cell migration and interaction, cancer cell invasion, drug delivery assays, wound healing, angiogenesis, thrombosis, studies of blood flow and shear stress etc. The vascular endothelium is considered as a complex organ, which is responsible for the dynamic control of vessel functions. The endothelium is continuously exposed both to shear stress and changes in pressure, including rhythmic fluctuations due to heart beating and to the signals from surrounding tissues. The luminal surface of endothelial cells is coated by gel-like endothelial glycocalyx layer. It is currently known that its main functions include modulation of vessel permeability to water and macromolecules ; mechanotransduction of fluid shear stress and pressure to the endothelial cytoskeleton and regulation of shear stress-mediated NO production ; regulation of red and white blood cells’ adhesion as well as modulation of the inflammatory response via binding of inflammatory factors. In order to test endothelial cells’ behavior in a three dimensional dynamic model reproducing the influence of physiological flow and shear stress as an important part of “everyday life” of the endothelium, we developed and tested a “microvasculature-on-a-chip” microfluidic device and performed several tests to verify its possible biomedical applications. We confirmed possibility to implement our chip to study changes in endothelium permeability in order to study capillary leak syndrome, and the endothelial remodeling in response to changes in glucose concentration like what happens during diabetes mellitus disease. We shall show that our system presents a promising tool to thoroughly study endothelial cells and its interaction with blood.

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