Platelet accumulation in an endothelium-coated elastic vein valve model of deep vein thrombosis is mediated by GPIbα—VWF interaction

Abstract

Deep vein thrombosis is a life-threatening disease that takes millions of people's lives worldwide. Given both technical and ethical issues of using animals in research, it is necessary to develop an appropriate in vitro model that would recapitulate the conditions of venous thrombus development. We present here a novel microfluidics vein-on-a-chip with moving valve leaflets to mimic the hydrodynamics in a vein, and Human Umbilical Vein Endothelial Cell (HUVEC) monolayer. A pulsatile flow pattern, typical for veins, was used in the experiments. Unstimulated human platelets, reconstituted with the whole blood, accumulated at the luminal side of the leaflet tips proportionally to the leaflet flexibility. Platelet activation by thrombin induced robust platelet accrual at the leaflet tips. Inhibition of glycoprotein (GP) IIb-IIIa did not decrease but, paradoxically, slightly increased platelet accumulation. In contrast, blockade of the interaction between platelet GPIbα and A1 domain of von Willebrand factor completely abolished platelet deposition. Stimulation of the endothelium with histamine, a known secretagogue of Weibel-Palade bodies, promoted platelet accrual at the basal side of the leaflets, where human thrombi are usually observed. Thus, platelet deposition depends on the leaflet flexibility, and accumulation of activated platelets at the valve leaflets is mediated by GPIbα-VWF interaction.

Movable typing of full‐lumen personalized Vein‐Chips to model cerebral venous sinus thrombosis

“…Importantly, our approach holds distinct advantages over traditional in vitro models, as these typically exhibit rectangular cross-sectional areas, having significantly different shear profiles when compared to circular vessels in vivo. [31,37,38] While embedded [39] and coaxial printing [40,41] techniques can generate micronsized blood vessels, replicating patient-specific geometries remains a challenge. Additionally, the substantial costs and single-use nature of these devices present further hurdles.…”

Novel therapeutics and emerging technology in haemostasis and thrombosis: highlights from the British society for haemostasis and thrombosis annual meeting

“…Dr Adela Constantinescu-Bercu (University College London, UK) shared a novel microfluidic assay for monitoring TTP patients. Hosam Alden Baksamawi, (University of Birmingham, UK) showed the endothelial cell-coated microfluidic chamber he has developed which models the moving valve leaflets and hydrodynamics of a large vein ( 23 ). He convincingly demonstrated GPIbɑ-dependent development of thrombi on the valve leaflets under “back and forth” venous flow.…”