Sciatic nerve remyelination and nodal formation following olfactory ensheathing cell transplantation

SCIATIC NERVE REMYELINATION AND NODAL FORMATION FOLLOWING OLFACTORY ENSHEATHING CELL TRANSPLANTATION. Mary A. Dombrowski, Masanori Sasaki, Karen L. Lankford, Hajime Tokuno, Christine Radtke, Jeffery D. Kocsis. Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT. Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome through axonal regeneration, remyelination, and neuroprotection. However, because little is known of the fate of OECs transplanted into injured peripheral nerve, their myelin forming potential requires investigation. To study these issues OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesions. Five weeks to six months after transplantation the nerves were studied histologically and it was determined that GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. Immunostaining revealed a high density of isoform Nav1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. Immunoelectron microscopy for GFP revealed transplanted OECs form peripheral type myelin. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve, form myelin on regenerated peripheral nerve fibers, and reconstruct nodes of Ranvier with proper sodium channel structure.