The transfection of multipotent neural precursor/stem cell transplant populations with magnetic nanoparticles

Abstract

Multipotent neural precursor/stem cells (NPCs) are a major transplant population with key properties to promote repair in several neuropathological conditions. Magnetic nanoparticle (MNP)-based vector systems, in turn, offer a combination of key benefits for cell therapies including (i) safety (ii) delivery of therapeutic biomolecules (DNA/siRNA) enhanceable by 'magnetofection' approaches (iii) magnetic cell targeting of MNP-labelled cells to injury sites and (iv) non-invasive imaging of MNP-labelled transplant populations for cell tracking. However, the applications of the versatile MNP platform for NPC transplantation therapies have received limited attention so far. We have evaluated the potential of MNP vectors for gene transfer to NPCs using a neurosphere culture model system; we also assessed repeat transfection ("multifection") and repeat transfection plus applied magnetic field ("magneto-multifection") strategies [to enhance transfection efficiency]. We show for the first time that MNPs can safely mediate single/combinatorial gene delivery to NPCs. Multifection approaches significantly enhanced transfection with negligible toxicity; no adverse effects were observed on stem cell proliferation/differentiation. "Multifected" NPCs survived and differentiated in 3D neural tissue arrays post-transplantation. Our findings demonstrate that MNPs offer a simple and robust alternative to the viral vector systems currently used widely to transfect neural stem cells in neurobiology/neural transplantation research.