Olfactory Ensheathing Cell Transplantation Into Spinal Cord Prolongs the Survival of Mutant SOD1(G93A) ALS Rats Through Neuroprotection and Remyelination

Amyotrophic lateral sclerosis (ALS) is a progressively fatal, incurable, neurodegenerative disorder. In this study, we investigated whether olfactory ensheathing cells (OEC) transplantation could provide protection to motor neurons and enable remyelination in mutant SOD1(G93A) transgenic rats with ALS. Seventy-two rats were divided into four groups: SOD1(G93A) rats (n = 20); medium+SOD1(G93A) rats (n = 20); OECs+SOD1(G93A) rats (n = 24); and another eight wild-type rats were used as controls. About 5 mu L (1 x 10(5)) OECs in DF12 medium was injected into the dorsal funiculus of the thoracic spinal cord at a predetermined depth. Survival analysis revealed a significant increase in the survival time in OEC+SOD1(G93A) rats. Body weight records and inclined board test showed a significant difference between OEC+SOD1(G93A) and SOD1(G93A) from the onset at 7 days to 11 days (P < 0.05). Four weeks following transplantation, motor neuron counts in the ventral horn of the spinal cord noted a significant motor neuron loss in SOD1(G93A) rats when compared with wild-type rats (P < 0.001), and much less neuronal loss and collapse was noted in OEC+SOD1(G93A) rats when compared with SOD1(G93A) rats(P < 0.001); immunohistochemistry and Western blot analysis of choline acetyltransferase supported the motor neuron count. Images of confocal microscope indicated that the transplanted OECs had survived for more than 4 weeks and migrated 4.2 mm through the spinal cord. Evidence of remyelination of transplanted OEC was captured with triple fluorescence labeling of green fluorescent protein, neurofilament, and myelin basic protein and was further confirmed by Western blot analysis of MPB. In conclusion, the transplanted OECs could serve as a source of neuroprotection and remyelination to modify the ALS microenvironment. Anat Rec, 294: 847-857, 2011. (C) 2011 Wiley-Liss, Inc.Anatomy & MorphologySCI(E)7ARTICLE5847-85729