Development of a fully humanised model for understanding platelet function

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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.