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

减少和替代小鼠用于模拟人体血小板体内反应

• 批准号: G0900732/1
• 负责人: Michael Emerson
• 金额: $ 28.62万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900732%2F1
• 关键词: Reducing; replacing; mouse; use; model

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.

在英国，大量的老鼠被用来研究肺栓塞等心血管疾病。肺栓塞发生在卧床不起的病人腿部或偶尔在经济舱长途飞行后形成血栓。直到最近，对肺栓塞原因的研究都是在小鼠中进行的，方法是在清醒的动物中诱导大量肺栓塞，以诱导死亡或瘫痪。早期的NC 3Rs资助使我们能够改进这种方法，使其既不会引起死亡也不会引起瘫痪，并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，并将人类细胞注入小鼠体内。我们将进行实验，以证明在我们的人-小鼠模型中形成的血凝块代表人类疾病。我们还将证明，药物（如阿司匹林）的作用可以通过将药物给予人类志愿者而不是通过反复强制将其引入小鼠的胃中来评估。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。由于许多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小鼠使用减少将放大数倍。