The development and application of non-invasive imaging technologies for investigating the behaviour of administered stem cells

该项目与“生物技术”部门保持一致，属于“先进材料”和“再生医学”这八大技术中的两个领域。该项目正在应对的具体挑战是“尖端医疗保健和医学”，专注于先进成像技术的开发和应用，以追踪被管理的干细胞的命运。该项目将基于UOL在干细胞/成像/纳米探针开发方面的专业知识，专注于多功能成像探针的开发和应用，以跟踪被管理细胞的行为，并调查它们与先天免疫系统的关键效应细胞的相互作用。我们和其他人最近的工作表明，在全身给药后，大多数细胞在24小时内死亡，但仍然可以有长期的治疗效果(Santeramo等人，干细胞转化医学，2017)。有证据表明，受控细胞的主要作用是调节巨噬细胞等先天免疫细胞，但这些相互作用的性质尚不清楚。更好地理解潜在的机制需要新的成像策略，使给药细胞和巨噬细胞能够同时在体内使用非侵入性成像进行成像。对原代巨噬细胞进行成像特别具有挑战性，因为细胞的表型在一周后开始改变。为此，无法引入萤火虫荧光素酶等遗传记者，使监测全身分布变得困难。虽然原代巨噬细胞可以用超顺磁性氧化铁纳米颗粒(SPIONS)等磁共振造影剂进行标记，但由于MR的时间分辨率和灵敏度较低，使用这项技术进行全身成像是不可行的，相反，它往往用于肾脏或脑等特定器官的成像。因此，该项目的最初目标将是设计具有核示踪剂功能的Spion探针，使其既能用正电子发射断层扫描(PET)监测巨噬细胞的全身分布，又能用MR监测器官内的生物分布。

The project aligns with the 'Biotechnology' sector, within the areas of 'Advanced Materials' and 'Regenerative Medicine' which are two of the 'Eight Great Technologies'. The specific challenge the project is addressing is 'Leading-edge healthcare and medicine', focussing on the development and application of advanced imaging technologies to track the fate of administered stem cells.Building on UoL's expertise in stem cells/imaging/nanoprobe development, the project will focus on the development and application of multifunctional imaging probes to track the behaviour of administered cells and investigate their interactions with key effector cells of the innate immune system. Recent work by ourselves and others have shown that following systemic administration, most cells die within 24h, but nevertheless can have long-lasting therapeutic effects (Santeramo et al, Stem Cells Translational Medicine, 2017). Evidence suggests that the main effect of the administered cells is to modulate innate immune cells such as macrophages, but it is not clear what the nature of these interactions are. Greater understanding of the underlying mechanisms requires novel imaging strategies that enable both the administered cells and the macrophages to be imaged simultaneously in vivo using non-invasive imaging. Imaging primary macrophages is particularly challenging because the phenotype of the cells starts to change after one week. For this reason, it is not possible to introduce genetic reporters, such as firefly luciferase, making it difficult to monitor the whole body distribution. Although primary macrophages can be labelled with magnetic resonance (MR) contrast agents such as superparamagnetic iron oxide nanoparticles (SPIONs), due to the poor temporal resolution and low sensitivity of MR, it is not feasible to use this technology for whole-body imaging, and instead, it tends be used for imaging specific organs such as the kidneys or brain. Therefore, an initial goal of the project will be to design SPION probes functionalised with a nuclear tracer to enable both the whole body distribution of macrophages to be monitored with positron emission tomography (PET) and intra-organ biodistribution to be monitored with MR.