2 research outputs found
Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting
Cell-based therapy exploits modified human cells to treat diseases but its targeted application
in specific tissues, particularly those lying deep in the body where direct injection is not
possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to
direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour
sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic
iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the
tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into
tumours, resulting in increased tumour macrophage infiltration and reduction in tumour
burden and metastasis. Our study indicates that clinical MRI scanners can not only track the
location of magnetically labelled cells but also have the potential to steer them into one or
more target tissues
A novel magnetic approach to enhance the efficacy of cell-based gene therapies
Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enhance the uptake of such ‘therapeutically armed’ cells by tumours. Monocytes naturally migrate from the bloodstream into tumours, so attempts have been made to use them to deliver therapeutic genes to these sites. However, transfected monocytes injected systemically fail to infiltrate tumours in large numbers. Using a new in vitro assay for assessing monocyte extravasation, we show that the ability of transfected human monocytes to migrate across a human endothelial cell layer into a 3D tumour spheroid is markedly increased when cells are pre-loaded with MNPs and a magnetic force is applied close to the spheroid. Furthermore, systemic administration of such ‘magnetic’ monocytes to mice bearing solid tumours led to a marked increase in their extravasation into the tumour in the presence of an external magnet. This new magnetic targeting approach could be used to increase the targeting, and thus the efficacy, of many cell-based gene therapies in vivo