we have recently shown that intravenously-injected adult undifferentiated mouse neural stem cells (aNSCs) promote multifocal remyelination and functional recovery in mice affected by a chronic form of experimental autoimmune encephalomyelitis (EAE). Here we evaluated the in vivo tracking of magnetically labelled aNSCs by serial MRI scans along the post-transplantation follow up.
METHOD AND MATERIALS
aNSCs were labelled with 0.1 mg/ml of iron by incubation with poli-L-lysine (PLL) and super paramagnetic iron oxide (SPIO) particles (Endorem, Guebert) for 72 hours. 12 C57BL/6 mice were immunized with MOG35-55 in Complete freund’s adjuvant and 6 of them – at the onset of clinical signs suggestive of CNS demyelination - underwent intravenous injection of 1000000 labelled aNSCs. Longitudinal MR scans (at day 0, 10, 15, 20, 25, and 30 from the immunization) were taken along the study using a commercially available human 3T scanner adapted with an animal-dedicated surface coil. Neurological evaluation was carried out during all this period. Neuropathological analysis (Prussian blue) of the CNS of transplanted EAE mice was also performed at sacrifice.
magnetically labelled aNSCs were identified in the transplanted mice as small hypointense spots within the white matter lesions as early as one day after the i.v. injection but progressively fade out at either 5 or 10 days post-transplantation. Neuropathology confirmed the presence of iron-labeled transplanted cells within areas of demyelination and axonal damage. All 6 EAE mice transplanted with labelled aNSCs showed an almost complete recovery from the disease, while untreated EAE mice showed disease progression and important disability.
early temporal and spatial migration of i.v. administered SPIO-labelled neural stem cells can be monitored by MRI. Magnetically labelled aNSCs may induce disease recovery in a chronic mouse model of multiple sclerosis. SPIOs tracers may represent an helpful tool for tracking transplanted neural stem cells in either pre-clinical or clinical studies in both animal models and humans.