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

在英国，大量的老鼠被用于研究心血管疾病，如肺栓塞。当卧床不起的病人的腿部形成血块时，或者偶尔在乘坐经济舱长途飞行后，就会发生肺栓塞。直到最近，对肺栓塞原因的研究都是在小鼠身上进行的，方法是在有意识的动物身上诱导大量肺栓塞，导致死亡或瘫痪。早期的NC3Rs拨款允许我们改进这种方法，使其既不会导致死亡也不会导致瘫痪，而且整个过程完全在全身麻醉下进行。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，并在其他小鼠中监测这些细胞。我们现在想证明，我们可以通过使用人类血液中的细胞而不是动物组织来减少动物的使用，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形成的血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通过给人类志愿者服用来评估，而不是反复强行将其引入小鼠的胃中。除了减少动物使用外，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。由于许多研究小组已将我们的方法纳入他们的研究计划，在我们自己的实验室中实现的小鼠使用减少将被放大几倍。

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.