Targeted delivery and MRI tracking of magnetically labelled cells.
Doctoral thesis, UCL (University College London).
The realisation of the therapeutic potential of cellular therapies will depend on our ability to deliver these cells to selected positions in the body where they can find a suitable micro-environment to flourish. Additionally our scientific understanding would befit from studies which can assess the behaviour of cells at specific locations inside the body. Magnetic cell delivery is a potential technology which might allow realising these premises. The major advantage of magnetic delivery compared to other delivery strategies is the ability to spatially localise entities in the body via externally applied magnetic fields. However, the fast decline of these fields with increasing distances is posing a major challenge for its in vivo application. The aim of this thesis was to investigate potential magnetic delivery approaches which can circumvent some of the typical limitations of this technique. Two different approaches were explored to this end. The first approach was evaluating the feasibility of a magnetic resonance imaging (MRI) system to steer labelled cells in arteries. Such an approach could take advantage of the imaging capabilities of magnetic resonance systems and combine these with steering to interactively guide cells or other entities of interest to a target area. The second approach was addressing the feasibility of theoretical optimisations and the scalability of experimental results. For that, human MRI data was used to derive geometrical models of the blood vessels to which cells were to be delivered in this scenario. Finite element modelling was then used to explore potential magnet arrangements with the aim to maximise the force acting on cells over all target vessels. The best performing arrangement was then used for computational fluid dynamics simulations to test the possibility of cell capture from the flowing blood stream. Finally the possibility to scale-down such an arrangement to the dimensions of an animal model without changing the forces acting on cells was investigated. Cells have to be labelled with magnetic materials in order to allow their magnetic actuation. This magnetic materials cause a distinctive contrast on MRI images. The potential of this imaging modality for cell tracking has been illustrated with an in vivo example for cell tracking in a rat heart and an in vitro example for a tissue engineering application. Experiments with a preclinical MRI system illustrated the feasibility of cell steering with MRI indicating that such an approach could be useful for magnetic cell delivery. Computational models for the evaluation of magnet arrangements allowed the in-silico assessment of their potential and could be used to improve the experimental design of pre-clinical studies.
|Title:||Targeted delivery and MRI tracking of magnetically labelled cells|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of BEAMS > Faculty of Maths and Physical Sciences > CoMPLEX - Maths and Physics in the Life Sciences and Experimental Biology|
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