Background: Spinal cord injury (SCI) generally results in necrosis, scarring, cavitation, and a release of inhibitory molecules of the nervous system, which lead to disruption of neurotransmission and impede nerve fiber regeneration. This study was intended to evaluate the therapeutic efficacy rates of the transplantation of NEP1-40- and NT-3 gene-co-transduced neural stem cells (NSCs) in a rat model of SCI.
Methods: Ninety Sprague-Dawley rats were subdivided randomly into six groups: sham-operated, SCI model, SCI + NSCs-NC, SCI + NEP1-40-NSCs, SCI + NT-3-NSCs, and SCI + NEP1-40/NT-3-NSCs. Motor function at different time points was evaluated using the Basso, Beattie, and Bresnahan locomotor activity scoring system (BBB). At 8 weeks post-transplantation, histological analysis, a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, immunofluorescent assay, immunocytochemical staining, and cholera toxin subunit B (CTB) retrograde tracing were performed.
Results: BBB scores of the co-transduction group significantly surpassed those of other transplantation groups and of the SCI-model group after 2 weeks post-transplantation. The apoptotic rate of neurocytes was significantly lower in the co-transduction group than in other experimental groups. Expression of NF-200, MBP, and ChAT was significantly higher in the SCI + NEP1-40/NT-3-NSCs group than in other transplantation groups, whereas the expression of GFAP and GAD67 was the second lowest after the sham-operated group. CTB retrograde tracing showed that CTB-positive neural fibers on the caudal side of the hemisected site were more numerous in the SCI + NEP1-40/NT-3-NSCs group than in other experimental groups.
Conclusion: Transplantation of NEP1-40- and NT-3-gene-co-transduced NSCs can modify the protein expression following acute SCI and promote neuron formation and axonal regeneration, thus having a neuroprotective effect. Furthermore, this effect surpasses that of transplantation of single-gene-transduced NSCs. Transplantation of NEP1-40- and NT-3-gene-co-transduced NSCs is effective at the neural recovery of the rat model of SCI and may be a novel strategy for clinical treatment of SCI.
Keywords: NEP 1–40; NT-3; spinal cord injury; transplantation.