Deploying clinical grade magnetic nanoparticles with magnetic fields to magnetolabel neural stem cells in adherent versus suspension cultures

Abstract

Neural stem cells (NSCs) have a high therapeutic potential for patients with neurological disease/injury given their neuroregenerative and immunomodulatory capabilities. In recent years, magnetic nanoparticles (MNPs) have been used as contrast agents in translational studies, to track transplanted NSCs using non-invasive magnetic resonance imaging (MRI). However, NSC uptake of MNPs is inherently low in the absence of chemical/biological uptake enhancing strategies such as cell targeting peptides and transfection agents - Approaches which may be cytotoxic and alter cellular physiology. By contrast, physical delivery strategies relying on magnetic assistive methods can safely enhance MNP uptake into multiple neural cell types. The utility of this approach has been demonstrated for gene delivery grade particles but their application in enhancing 'magnetolabelling' with clinical grade contrast agents has never been evaluated. Here, we show that applied oscillating magnetic fields can safely enhance the uptake of a clinical grade MNP (Lumirem/Ferumoxsil) into NSCs propagated as neurospheres (suspension cultures, the preferred format for transplantation) but offer limited benefit for monolayer (adherent) cultures. This physical delivery method therefore has potential to facilitate cell labelling for clinical therapies.