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

止血是控制血液凝结的重要生物过程。这是一个复杂的过程，涉及血管壁、血液中的细胞和血浆中循环的蛋白质。了解止血是如何调节的是至关重要的，因为当止血出现问题时，可能会导致危及生命的出血或血栓。目前，研究影响止血的因素的主要方法是使用尾部出血模型。这包括切断啮齿动物尾巴的末端，并计算止血需要多长时间。然后，可以在动物身上测试不同的药物和治疗方法，看看它们是否改变了出血时间。这些实验是非常多变的，因此需要大量的动物。由于啮齿类动物和人类在生物学上存在许多差异，它们也不能很好地代表人类的止血。本研究的目的是开发一种替代止血模型，使用人类血液和人类血管来取代尾巴出血模型。为了做到这一点，我们将从胎盘中取出人体血管，这些血管通常在婴儿出生后被丢弃。我们将从血管中冲洗现有的血液，并通过它输送人类捐赠者的血液。当血液通过血管时，我们会用一根小针刺穿血管壁，造成出血。这将刺激血液凝块的形成，我们将计算止血需要多长时间。除了在我们的人体止血模型中测量出血时间之外，我们还将使用高倍显微镜详细观察血液凝块的组成。这将告诉我们更多关于止血过程和如何控制止血的信息。为了使其他科学家能够使用我们的模型并产生更大的影响，减少研究中使用的动物数量，他们需要接触到人类胎盘血管。因此，我们将测试不同的血管储存方法，以便血管可以储存更长时间，科学家可以在不接触新鲜胎盘的情况下使用该模型。综上所述，这项研究将提供一种不使用动物来测量止血的新方法。它还将产生更可靠的结果，并提供有关如何控制止血的更详细信息。使用人体血液和人体血管也意味着，与目前的尾巴出血模型相比，结果与人类止血更相关。

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.