MRI scans were performed in the Lewis rat experimental allergic encephalomyelitis (EAE) model in which magnetically labeled mouse embryonic stem cells (ESC) were implanted into lateral ventricles of the brain. MR imaging performed at clinically relevant magnetic field strength demonstrated extensive migration of magnetically labeled grafted ESC along the ventricles and into the corpus callosum of these animals. MR images were correlated with histopathologic staining for iron, myelin, oligodendrocytes, astrocytes, and microglia. Both the Prussian blue and myelin staining closely matched the area of contrast enhancement seen on the MR images. Magnetically labeled encephalotigenic lymphocytes were intravenously infused as part of an adoptive transfer model of EAE in the mouse. Infiltration of labeled cells into the spinal cord and nerve roots of neurologically impaired mice was detected using in vivo magnetic resonance microscopy at 7T. This is the first demonstration of being able to track activated lymphocytes into the central nervous system in an autoimmune disease model and opens the possibility of monitoring the trafficking of pharmaceutically or genetically engineered cells into the brain to further the understanding of the pathophysiology of EAE and the pre-clinical evaluation of new cell-based therapies. Studies performed using magnetically labeled lymph node derived cells in the marmoset EAE model have shown the ability to detect labeled cells in the brain and spinal cord on a clinical MRI scanner. These results will serve as the basis for moving forward to magnetically label cells harvested during apheresis and re-infuse autologous cells into patients with MS to monitor the migration of labeled stem cells or peripheral blood mononuclear cells into the central nervous system by MRI. Serial MRI studies performed in the marmoset model experimental autoimmune encephalomyelitis (EAE) are used for pre-clinical evaluation of macrophage inhibitory molecule (MIM) for multiple sclerosis (MS). Macrophages are an important component in MS and EAE lesion development and inhibition of the migration of macrophages into the brain may have an important role in down regulating the inflammatory processes. Preliminary results comparing MIM to placebo in the EAE marmoset model using clinical, pathologic and MRI evaluations as outcome measures revealed a possible advantage in the treated animals versus placebo treated animals in severity of disease. Future studies are planned of using the EAE marmoset model as basis for harvesting stem cells and transplantation to determine if these cells will stimulate remyelination in EAE lesions.
