Journal
NEUROSCIENCE LETTERS
Volume 644, Issue -, Pages 67-75Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2017.02.034
Keywords
Cell-mediated gene therapy; Adenoviral vector; Spinal cord injury; Mini pigs; Human umbilical cord blood mononuclear cell; Vascular endothelial growth factor (VEGF); Glial cell-derived neurotrophic factor (GDNF); Neural cell adhesion molecule (NCAM)
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Funding
- Russian Science Foundation [16-15-00010]
- Russian Science Foundation [16-15-00010] Funding Source: Russian Science Foundation
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Currently, in clinical practice there is no efficient way to overcome the sequences of neurodegeneration after spinal cord traumatic injury. Using a new experimental model of spinal cord contusion injury on miniature pigs, we proposed to deliver therapeutic genes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) to the damaged area, using umbilical cord blood mononuclear cells (UCBC). In this study, genetically engineered UCBC (2 x 10(6) cells in 200 ml of saline) were injected intrathecally to mini-pigs 10 days after SO. Control and experimental mini pigs were observed for 60 days after surgery. Histological, electrophysio-logical, and clinical evaluation demonstrated significant improvement in animal treated with genetically engineered UCBCs. Difference in recovery of the somatosensory evoked potentials and in histological findings in control and treated animals support the positive effect of the gene-cell constriction for recovery after spinal cord injury. Results of this study suggest that transplantation of UCBCs simultaneously transduced with three recombinant adenoviruses Ad5-VEGF, Ad5-GDNF and Ad5-NCAM represent a novel potentially successful approach for treatment of spinal cord injury. (C) 2017 Elsevier B.V. All rights reserved.
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