Magnetic Nanoparticle-Mediated Gene Transfer to Oligodendrocyte Precursor Cell Transplant Populations Is Enhanced by Magnetofection Strategies

Abstract

This study has tested the feasibility of using physical delivery methods, employing static and oscillating field "magnetofection" techniques, to enhance magnetic nanoparticle-mediated gene transfer to rat oligodendrocyte precursor cells derived for transplantation therapies. These cells are a major transplant population to mediate repair of damage as occurs in spinal cord injury and neurological diseases such as multiple sclerosis. We show for the first time that magnetic nanoparticles mediate effective transfer of reporter and therapeutic genes to oligodendrocyte precursors; transfection efficacy was significantly enhanced by applied static or oscillating magnetic fields, the latter using an oscillating array employing high-gradient NdFeB magnets. The effects of oscillating fields were frequency-dependent, with 4 Hz yielding optimal results. Transfection efficacies obtained using magnetofection methods were highly competitive with or better than current widely used nonviral transfection methods (e.g., electroporation and lipofection) with the additional critical advantage of high cell viability. No adverse effects were found on the cells' ability to divide or give rise to their daughter cells, the oligodendrocytes-key properties that underpin their regeneration-promoting effects. The transplantation potential of transfected cells was tested in three-dimensional tissue engineering models utilizing brain slices as the host tissue; modified transplanted cells were found to migrate, divide, give rise to daughter cells, and integrate within host tissue, further evidencing the safety of the protocols used. Our findings strongly support the concept that magnetic nanoparticle vectors in conjunction with state-of-the-art magnetofection strategies provide a technically simple and effective alternative to current methods for gene transfer to oligodendrocyte precursor cells.