Reducing and replacing mouse use to model the human platelet response in vivo

在英国，大量的小鼠被用来研究肺栓塞等心血管疾病。当卧床不起的患者或偶尔在经济舱长途飞行后腿部形成血块时，就会发生肺血栓。直到最近，对小鼠肺栓塞原因的研究是通过在清醒动物中诱导大量肺栓塞来导致死亡或瘫痪来进行的。早期的NC3Rs拨款允许我们改进这种方法，这样既不会导致死亡，也不会导致瘫痪，手术完全是在全身麻醉下进行的。然而，我们的方法确实需要大量的小鼠死亡，因为我们必须从它们的血液中收集细胞，并在更多的小鼠中监测这些细胞。我们现在想要证明，我们可以通过使用来自人类血液而不是动物组织的细胞来减少动物的使用，并将人类细胞注入老鼠体内。我们将进行实验，以证明在我们的人-鼠模型中，血液凝块以一种代表人类疾病的方式形成。我们还将证明，阿司匹林等药物的效果可以在小鼠身上进行评估，方法是给人类志愿者服用这种药物，而不是反复强行将其引入小鼠的胃中。除了减少动物使用，这项研究还将使我们能够以一种全新的方式处理患者样本，这可能有助于心血管研究。由于一些研究小组已经将我们的方法纳入他们的研究计划，我们自己的实验室实现的老鼠使用量的减少将扩大几倍。

Huge numbers of mice are used in the UK to research cardiovascular diseases such as pulmonary embolism. Pulmonary embolism occurs when blood clots form in the legs of bed-ridden patients or occasionally following a long flight in economy class. Until recently research into the causes of pulmonary embolism was carried out in mice by inducing massive pulmonary embolism in conscious animals to induce death or paralysis. An earlier NC3Rs grant allowed us to refine this method so that neither death nor paralysis was induced and the procedure was conducted entirely under general anaesthesia. Our method does, however, require the death of large numbers of mice since we must collect cells from their blood and monitor these cells in additional mice. We want to show now that we can reduce animal use by using cells from human blood rather than animal tissues and infuse the human cells into mice. We shall conduct experiments to demonstrate that blood clots form in our human-mouse model in a way that represents human disease. We shall also demonstrate that the effects of drugs such as aspirin can be evaluated in the mouse by giving the drug to human volunteers rather than by repeatedly and forcibly introducing it to the stomachs of mice. As well as reducing animal use this research will allow us to work with patient samples in an entirely new way which may contribute to cardiovascular research generally. Since a number of research groups have incorporated our methods into their research plans the reduction in mouse use achieved in our own laboratory will be amplified several fold.