Method article: an in vitro blood flow model to advance the study of platelet adhesion utilizing a damaged endothelium
Method article: an in vitro blood flow model to advance the study of platelet adhesion utilizing a damaged endothelium
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DOI：
10.1080/09537104.2021.1988550
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发表时间：
2021-12-19
期刊：
影响因子：
3.3
通讯作者：
Eniola-Adefeso, Omolola
中科院分区：
文献类型：
--
作者：
Banka, Alison Leigh;Eniola-Adefeso, Omolola
利用微流控装置的体外流量测定通常用于研究人类血小板，作为昂贵的止血和血栓形成动物模型的替代方法，这些模型可能不能准确地代表体内人类血小板的行为。在这里，我们提出了一个可调的体外模型来研究血小板在人类全血流动中的行为，包括炎症、受损的内皮和暴露的细胞外基质。我们证明，该模型适用于各种抗凝血剂、剪切速率和内皮细胞培养的蛋白质，而不需要复杂的定制设计设备。此外，我们验证了这种“内皮受损”模型作为筛选P2Y（12）受体拮抗剂（替格瑞洛）、泛选择素抑制剂（Bimosiamose）和组胺受体拮抗剂（西咪替丁）潜在抗血小板或抗血栓化合物的方法的能力。这些化合物显著降低血小板对受损内皮的粘附，表明该模型可以成功筛选直接靶向血小板或间接靶向内皮的抗血小板化合物。
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 P2Y(12) 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.