A human ex vivo model of haemostasis: A replacement for rodent tail bleeding assays

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Haemostasis is the important biological process that controls blood clotting. It is a complicated process involving the blood vessel wall, cells in the blood and proteins circulating in plasma. Understanding how haemostasis is regulated is crucial, as when it goes wrong it can lead to life threatening bleeding or clotting.Currently the main way to investigate factors which affect haemostasis is by using the tail bleeding model. This involves cutting off the end of a rodents tail and timing how long it takes to stop bleeding. Different drugs and treatments can then be tested on the animals to see if they change the bleeding time. These experiments are very variable and therefore require lots of animals. They are also not a very good representation of haemostasis in humans as there are many biological differences between rodents and humans.The aim of this study is to develop an alternative haemostasis model that uses human blood and human blood vessels to replace the tail bleeding model. To do this we will take human blood vessels from placentas, which are usually discarded following the birth of a baby. We will flush out existing blood from the vessel and flow human donor blood through it. When blood is passing through the vessel, we will use a small needle to puncture the blood vessel wall causing bleeding. This will stimulate the formation of a blood clot and we will time how long it take to stop bleeding. As well as measuring bleeding time in our human haemostasis model, we will also use high power microscopes to look in detail at what the blood clots are made up of. This will tell us more information about the process of haemostasis and how it is controlled. To enable other scientists to use our model and have a greater impact reducing the number of animals used in research, they need access to human placental vessels. We will therefore test different ways of storing the blood vessels, so that vessels can be stored for longer and scientists can use the model without access to fresh placentas.In summary, this study will provide a new way to measure haemostasis that does not use animals. It will also produce more reliable results and provide more detailed information about how haemostasis is controlled. The use of human blood and human blood vessels also means that the results are more relevant to human haemostasis than the current tail bleeding model.