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

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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.