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”领域一致，属于“先进材料”和“再生医学”领域，这是“八大技术”中的两项。该项目正在解决的具体挑战是“领先的医疗保健和医学”，重点是开发和应用先进的成像技术来跟踪管理干细胞的命运。基于UoL在干细胞/成像/纳米探针开发方面的专业知识，该项目将专注于多功能成像探针的开发和应用，以跟踪给药细胞的行为，并研究它们与先天免疫系统关键效应细胞的相互作用。我们和其他人最近的研究表明，在系统给药后，大多数细胞在24小时内死亡，但仍然可以产生持久的治疗效果（Santeramo等人，干细胞转化医学，2017）。有证据表明，给药细胞的主要作用是调节先天免疫细胞，如巨噬细胞，但这些相互作用的性质尚不清楚。为了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在体内同时成像，使用非侵入性成像。原代巨噬细胞成像尤其具有挑战性，因为细胞的表型在一周后开始改变。因此，不可能引入萤火虫荧光素酶等遗传报告基因，因此难以监测其全身分布。虽然原代巨噬细胞可以用磁共振（MR）造影剂（如超顺磁性氧化铁纳米颗粒（SPIONs））进行标记，但由于MR的时间分辨率较差和灵敏度较低，因此无法将该技术用于全身成像，相反，它往往用于特定器官的成像，如肾脏或大脑。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，使巨噬细胞的全身分布能够用正电子发射断层扫描（PET）监测，器官内的生物分布可以用MR监测。

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.