Kyrtatos, P.; (2010) Cell targeting and imaging using magnetic nanoparticles. Doctoral thesis , UCL (University College London).

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Abstract

BACKGROUND AND AIMS. The success of stem cell therapies partly depends on the ability to deliver the cells to the site of injury. Circulating endothelial progenitor cells (EPCs) are involved in physiological processes such as vascular re-endothelialisation and post-ischaemic neovascularisation and have been utilised in several clinical trials. Superparamagnetic iron oxide particles have previously been used to label and track cells using magnetic resonance imaging (MRI), as well as to magnetically attract drugs and cells to desired sites. The aim of this PhD was to develop a methodology to magnetically attract EPCs, labelled with a clinically approved iron oxide agent, to a site of arterial injury using magnetic fields originating outside the body. METHODS AND RESULTS. Human EPCs were cultured in the presence of iron oxide superparamagnetic nanoparticles. A labelling method was developed that retained cell survival and differentiation, as indicated by metabolic activity and flow cytometry assays, as well as MRI visibility. Finite element modelling (FEM) computer simulations were performed to investigate the interaction of magnetic forces with hydrodynamic drag forces. FEM indicated successful external magnetic cell targeting from a vessel with flow rate similar to a rat common carotid artery; correspondingly there was a 6- fold increase in cell capture in an in vitro flow system. Angioplasty was performed on rat common carotid arteries to denude the endothelium and EPCs were administered with and without the presence of the external magnetic device during a 10 minute period of flow cessation. Targeting enhanced cell retention at the site of injury by 5-fold. CONCLUSIONS. Using an externally applied magnetic device, it is possible to enhance EPC localisation in a flowing sytem in vitro and to a flow-isolated site of common carotid artery injury in vivo, without affecting cell viability or differentiation in culture. This technology could be more widely adapted to localise and monitor cells in other organs and may provide a useful tool for systemic injection of cell therapies.

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