Why the study?
Animal models of hemostasis and thrombosis are costly and may not accurately represent human platelet behavior in vivo, prompting the need for alternative in vitro flow assays.
This tunable in vitro model successfully screens anti-platelet compounds targeting platelets or the endothelium, offering an alternative to animal models.
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May enable human platelet studies without animal models; leaves open clinical translation in thrombosis.
In vitro flow assays utilizing microfluidic devices are often used to study human platelets as an alternative to the costly animal models of hemostasis and thrombosis that may not accurately represent human platelet behavior in vivo. Here, we present a tunable in vitro model to study platelet behavior in human whole blood flow that includes both an inflamed, damaged endothelium and exposed extracellular matrix. We demonstrate that the model is adaptable across various anticoagulants, shear rates, and proteins for endothelial cell culture without the need for a complicated, custom-designed device. Furthermore, we verified the ability of this ‘damaged endothelium’ model as a screening method for potential anti-platelet or anti-thrombotic compounds using a P2Y12 receptor antagonist (ticagrelor), a pan-selectin inhibitor (Bimosiamose), and a histamine receptor antagonist (Cimetidine). These compounds significantly decreased platelet adhesion to the damaged endothelium, highlighting that this model can successfully screen anti-platelet compounds that target platelets directly or the endothelium indirectly.
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Banka et al. (2021) studied this question.
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