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Kevin Gregory-Evans, Urs Hafeli, Anat Yanai, Andrew Metcalfe, Cheryl Y. Gregory-Evans; Focused Mesenchymal Stem Cell Targeting Using Supraparamagnetic Iron Oxide Nanoparticles. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3417.
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Mesenchymal stem cells (MSCs) offer significant advantages for long-term release of therapeutic molecules into the diseased retina. We proposed to determine whether magnetization of cells offers better MSC delivery to the retina via the systemic circulation.
Bone-marrow MSCs for syngeneic rat littermates were cultured with magnetic nanoparticle fluidMAG-D. To allow for MSC identification in tissue culture, cells were also treated with Q-Tracker 655. Magnetised MSCs were injected into the tail vein of heterozygous S334ter-4 rhodopsin-mutant rats after a 3mm gold-plated neodymium disc magnet had been placed within the orbit, but outside the globe. Animals treated for up to one month were compared with those treated with non-magnetised MSCs and animals injected with vehicle only. MSCs were identified in retinal flatmounts and cryosections and retinal concentrations of neuroprotectant GDNF and CNTF and anti-inflammatory molecules IL10 and HGF were measured by ELISA.
Magnetic targeting of intravenously injected MSCs resulted in approximately 5 times more cells appearing in the neurosensory retina than when non-magnetic MSCs were used. This benefit was seen for at least one month post-injection. MSC seeding was seen particularly in the retina corresponding to the overlying, externally placed magnet. In addition, MSCs were not only found in the perivascular space, but also in all retinal layers. Significantly higher concentrations of CNTF, IL10 and HGF (but not GDNF) were detected in magnetised MSC-treated animals compared with non-magnetised MSC and vehicle treated animals (P<0.05).
Magnetic nanoparticle treatment allows for large numbers of systemically injected MSCs to be targeted to specific retinal loci and ELISA results suggest that such cells have significant neuroprotective and anti-inflammatory potential. Magnetic MSCs offer a safe, non-invasive and repeatable approach in the treatment of inflammatory and degenerative retinal diseases.
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