Reduction of use of experimental mice in type 1 diabetes research through non-invasive, in vivo longitudinal imaging

我们的实验室研究1型糖尿病（T1D），这是一种自身免疫性疾病，由人体自身免疫系统攻击胰腺中产生胰岛素的β细胞引起。一旦这些细胞被破坏，患者需要注射胰岛素来吸收葡萄糖。人工血糖监测和胰岛素注射不能平衡血糖水平和内源性生成，葡萄糖控制不良引起的并发症很常见。我们研究的目的是找到治疗这种疾病的方法。由于T1D是由免疫系统介导的，其中许多过程过于复杂，无法在体外系统中复制，因此我们的许多工作需要使用实验小鼠。由于即使在易患T1D的非肥胖糖尿病（NOD）小鼠品系中，疾病进展也不均匀，因此需要对大组小鼠进行评估，以确定治疗是否减少了胰岛的免疫浸润，或者是否改变了不同类型免疫细胞的比例。由于胰腺位于腹腔内，老鼠必须被挑选出来才能接近它，这意味着每个研究时间点都必须使用一组新的老鼠。我们的建议描述了使用一种全新的方法来研究移植到耳廓的胰岛的免疫浸润。该方法允许在不同时间点对同一胰岛进行非侵入性和重复调查。在任何治疗前后都可以对同一个体进行测量，这一事实消除了对大群体的需求，并且由于成像是非侵入性的，可以在多个时间点对同一个体进行测量，从而减少了所需的群体数量。我们相信，这项新技术将使我们能够用更少的实验动物收集到更高质量的数据。

Our laboratory studies Type 1 Diabetes (T1D), which is an autoimmune disease caused by an attack of the body's own immune system against the insulin producing beta cells in the pancreas. Once these cells are destroyed, patients need to inject insulin in order to take up glucose. Manual glucose monitoring and insulin injection cannot balance blood glucose levels as well as endogenous production, and complications arising from poor glucose control are common. The aim of our research is to discover a cure for this disease.As T1D is mediated by the immune system, and many of the processes involved are too complex to be replicated in an in vitro system, a lot of our work therefore requires use of experimental mice. As disease progression is not uniform even in the T1D prone non-obese diabetic (NOD) mouse strain, large groups of mice need to be assessed to determine if a treatment reduces immune infiltration in the islets, or if it changes the proportions of different types of immune cells. As the pancreas is situated within the abdominal cavity the mice have to be culled to access it, meaning that for every time point studied a fresh group of mice has to be used. Our proposal describes the use of a completely novel method for investigating immune infiltration into islets transplanted into the pinna of the ear. This method allows non-invasive and repeated investigation of the same islets at different time points. The fact that the same individual can be measured before and after any treatment removes the need for large group sizes, and as the imaging is non invasive the same individual can be measured at several time points, reducing the number of groups needed. We believe that this novel technique will allow us to collect better quality data using significantly fewer experimental animals.