MRI scans were performed in myelin deficient animals in which magnetically labeled progenitor oligodendrocytes were implanted into the spinal cord. 3D MR microscopy (MRM) was performed ex vivo on the spinal cords with 78 micron isotropic resolution at 4.7 Tesla. MR microscopy showed extensive migration (up to 8.4 mm) of magnetically labeled grafted cells, particularly in the area of the dorsal column. MR images were correlated with histopathologic staining for iron, myelin, astrocytes, and microglia. Both the Prussian blue and myelin staining closely matched the area of contrast enhancement seen on the MR images. Magnetically labeling precursor oligodendrocytes were implanted in the brains of dysmyelinated rats and cell proliferation and migration was noted at clinically relevant Magnetic Resonance Imaging 1.5 Tesla units. The labeled cells migrated along the surface of the lateral ventricle and into the olfactorary lobe of the rat brain. These cells penetrated into the white matter and myelinated axons as evident on Purssian blue staining and myelin stains. Mouse Embryonic stem cells (ESC) were labeled with magnetodendrimer and transplanted into a spinal cord crush injury model in collaboration with Dr. John McDonald. Magnetically tagged labeled cells migrated into area of crush injury and ESC?s were noted to differentiate into neuronal elements on immunohistochemical stains in rats euthanized by day 14 post-injury. MRI images at 4.7 Tesla were able to demonstrate the extent of migration along the damaged spinal cord. Further studies are planned to optimize the time and number of magnetically labeled cells needed for transplantation in this spinal cord crush injury model. Serial MRI studies performed in the marmoset model experimental autoimmune encephalomyelitis (EAE) are used for pre-clinical evaluation of new therapies for multiple sclerosis. The serial MRI studies have demonstrated week to week changes in the number and distribution of EAE lesions. MRI stereotactic directed biopsy techniques have been perfected that will allow us to biopsy EAE lesion for histopathologic evaluation of the cellular microenvironment of the EAE lesion. Studies are planned of using this model as basis for stem cell transplantation to determine if these cells will stimulate remyelination in EAE lesions.
