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:
Jun WU
1
;
Tian-Sheng SUN
;
Ji-Xin REN
;
Xian-Zhang WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Newborn; Brain Tissue Transplantation; methods; Cells, Cultured; DNA, Recombinant; therapeutic use; Disease Models, Animal; Female; Gene Transfer Techniques; Genetic Therapy; methods; Genetic Vectors; genetics; Graft Survival; genetics; Growth Cones; metabolism; ultrastructure; Nerve Regeneration; genetics; Neuroglia; metabolism; transplantation; Neurotrophin 3; biosynthesis; genetics; Olfactory Bulb; cytology; transplantation; Paralysis; metabolism; physiopathology; therapy; Plasmids; genetics; Rats; Rats, Wistar; Recovery of Function; genetics; Spinal Cord Injuries; metabolism; physiopathology; therapy; Treatment Outcome; Up-Regulation; genetics
- From: Neuroscience Bulletin 2008;24(2):57-65
- CountryChina
- Language:English
-
Abstract:
OBJECTIVECombine 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).
METHODSPrimary 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 4x10(5) 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.
RESULTSNT-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.
CONCLUSIONNon-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.
