Development of a fully humanised model for understanding platelet function

血小板是血液中的小细胞，当被激活时，在防止损伤部位过度出血方面发挥关键作用。相反，不适当的血小板活化会阻断心脏和大脑的血液供应，导致危及生命的心脏病发作或中风，并导致估计40%的心血管死亡。目前预防心脏病发作和中风的治疗是基于抑制正常血小板功能的药物。虽然对大约三分之二的患者有效，但其余的患者死于第二次心脏病发作或中风。由于抗血小板药物抑制正常的血小板功能，它们也可能具有讨厌的出血的不良副作用，这在某些情况下可能成为患者的严重并发症。因此，需要了解控制血小板活化和功能的分子机制以及血小板如何与受损的血管壁相互作用，以了解血小板如何影响健康和疾病，并确定新的和改进的药物靶点。直接在人体中研究这些事件是不道德的，血小板研究目前严重依赖于使用基因改变的小鼠模型来了解蛋白质或特定蛋白质结构域如何在血小板功能中发挥作用。然而，小鼠模型并不总是一个合适的替代研究人类血小板功能和人类血管的模型是必要的。该项目将首次汇集一个模型来复制人类血管，并使用一种允许人类血小板被修饰的方法。这将使新的药物靶点能够使用人体组织进行研究和测试，减少并取代心血管研究中的动物使用。

Platelets are small cells in the blood which, when activated, play a critical role in the prevention of excessive bleeding at sites of injury. Conversely, inappropriate platelet activation can block the blood supply to the heart and brain resulting in life threatening heart attacks or strokes and contribute to an estimated 40% of cardiovascular deaths. Current therapy in the prevention of heart attacks and strokes is based on drugs which suppress normal platelet function. While effective in approximately two thirds of patients, the remainder succumb to a second heart attack or stroke. As anti-platelet drugs suppress normal platelet function they can also have the undesirable side effect of nuisance bleeding, which can in some cases become a serious complication for patients. Therefore, an understanding of the molecular mechanisms governing platelet activation and function and how platelets interact with a damaged blood vessel wall is needed to understand how platelets impact health and disease and for the identification of new and improved drug targets. It is not ethical to study these events directly in people and platelet research is currently heavily reliant on the use of genetically altered mouse models to understand how proteins or specific protein domains play a role in platelet function. However, mouse models are not always a suitable alternative to investigate human platelet function and a model of the human blood vessel is needed. This project will, for the first time, bring together a model to replicate the human blood vessel with a method that will allow human platelets to be modified. This will enable new drug targets to be studied and tested using human tissue, reducing and replacing the use of animals in cardiovascular research.