By combining commonly used transfection agents (TA) that have high net positive electrostatic charge with Superparamagnetic dextran coated iron oxide nanoparticle (SPIO) such as the FDA approved agent Ferumoxides (FE), a complex is formed that can be used to magnetically label stem cells and other mammalian cells. Various concentrations of ferumoxides and poly-l-lysine (FE-PLL) complexes were initially used to magnetically label cells. No adverse effect on the cell viability and functional capacity or toxicity was observed following magnetic cell labeling with FE-PLL. Biodistribution studies of magnetically labeled human mesenchymal stem cells in rats demonstrated that labeled cells could be detected using a 1.5 Tesla clinical MR unit in the livers for up to 29 days following an intravenous infusion of 900,000 cells. FE-PLL labeled encephalotigenic T-cells were injected into recepient mice to induce experimental allergic encephalomyelitis (EAE) a mouse model of multiple sclerosis. FE-PLL labeled T-cells were detected in the spinal cords of EAE mice at time of initial neurological event using MR microscopy at 7 Tesla. Immmunohistochemical analysis revealed that magnetically labeled T-cells had similar proliferation assays and cytokine profiles as unlabeled encephalotigenic T-cells. In addition, there was excellent correlation between MR microscopy and histology of spinal cords in clinically affected animals. Protamine Sulfate (Pro) is an FDA approved drug that is used to treat heparin anticoagulation was found to be a more efficient transfection agent and when complexed to FE in labeling cells. FE-Pro labeled stem cells and other mammalian cells demonstrated no short or long-term toxicity, changes in differentiation capacity or cell function. Plans are underway to translate the magnetic labeling technique using a FDA approved MRI contrast agent Ferumoxides complexed to Pro to label autologous peripherial blood mononuclear cells or stem cells in order to monitor the temporal spatial of these cells for repair, replacement or therapy of central nervous system disease.
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