STAR BURST Dendrimers (D), and superparamagnetic iron oxide nanoparticles (SPIO) are being developed as magnetic labels for in vivo cellular imaging. By combining commonly used transfection agents (TA) that have high net electrostatic charges with macromolecular high generation (G) dendrimers (G =5, 7, 9, 10) were conjugated to DOTA and Gadolinium (III) ion or SPIO, effectively altering (by shielding water molecules) from interacting with the contrast agents nuclear magnetic resonance relaxation properties were detected. The physical chemical properties of the TA- SPIO molecules have been modeled and characterized and used to predict the electrostatic interaction between TA and the contrast agents and therefore the combination as a novel method for chaperoning contrast agents into endosomes in cells. 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 14 days following an intravenous infusion of 900,000 cells. Biochemical and molecular biological analysis of TA-SPIO labeled stem cells indicates that cell labeling did not effect proliferation or viability of the stem cells nor the cells ability to terminally differentiate under appropriate conditions. Using a similar magnetical labeling approach, enchephalotigenic T-cells were injected into recepient mice and experimental allergic encephalomyelitis was induced in these animals. Labeled T-cells could be detected in the spinal cords of EAE mice at time of initial neurological event using MR microscopy at 7 Tesla. Immmunohistochemical analysis revealed that TA-SPIO 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. Further studies are planned to determine if the trafficking of magnetically labeled stem cells or genetically altered cells can be detected by MRI and whether these cells will localize to, repair, repopulate or treat central nervous system diseases.
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