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，患者就需要注射胰岛素来摄取葡萄糖。手动血糖监测和胰岛素注射不能平衡血糖水平以及内源性产生，并且由血糖控制不良引起的并发症是常见的。我们研究的目的是发现这种疾病的治疗方法。由于T1D是由免疫系统介导的，并且所涉及的许多过程过于复杂，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T1D易感的非肥胖糖尿病（NOD）小鼠品系中疾病进展也不均匀，因此需要评估大组小鼠以确定治疗是否减少胰岛中的免疫浸润，或者是否改变不同类型免疫细胞的比例。由于胰腺位于腹腔内，因此必须挑选小鼠以接近它，这意味着对于研究的每个时间点，必须使用一组新鲜的小鼠。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相同胰岛进行非侵入性和重复研究。在任何治疗之前和之后都可以测量同一个人的事实消除了对大组大小的需要，并且由于成像是非侵入性的，可以在几个时间点测量同一个人，减少了所需的组的数量。我们相信，这项新技术将使我们能够使用更少的实验动物收集更高质量的数据。

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.