1. Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury
- Author
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Jun Wu, Xian-Zhang Wang, Tian-Sheng Sun, and Ji-xin Ren
- Subjects
animal structures ,Physiology ,Genetic Vectors ,Growth Cones ,DNA, Recombinant ,Neurotrophin-3 ,Neurotrophin 3 ,In vivo ,medicine ,Animals ,Paralysis ,Brain Tissue Transplantation ,Rats, Wistar ,Spinal cord injury ,Cells, Cultured ,Spinal Cord Injuries ,biology ,Chemistry ,General Neuroscience ,Graft Survival ,Gene Transfer Techniques ,General Medicine ,Genetic Therapy ,Recovery of Function ,Spinal cord ,medicine.disease ,Retrograde tracing ,Olfactory Bulb ,Olfactory bulb ,Cell biology ,Nerve Regeneration ,Rats ,Up-Regulation ,Disease Models, Animal ,medicine.anatomical_structure ,Treatment Outcome ,Animals, Newborn ,embryonic structures ,Immunology ,biology.protein ,Original Article ,Female ,Olfactory ensheathing glia ,Neuroglia ,Ex vivo ,Plasmids - Abstract
Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin-3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI). Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1(+)-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord (T9) contusion by the New York University impactor. The animals in 3 different groups received 4×105 OEG transfected with pcDNA3.1(+)-NT3 or pcDNA3.1(+) plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1(+)-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT-3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.
- Published
- 2008