PDF(Sci-hub)
Abstract：
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 (2×106 cells in 200 ml of saline) were injected intrathecally to mini-pigs 10days after SCI. Control and experimental mini pigs were observed for 60days after surgery. Histological, electrophysiological, 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.
摘要：
目前,在临床实践中，没有有效的方法来克服脊髓创伤性损伤后的神经变性。使用小型猪脊髓挫伤的新实验模型，我们建议提供编码血管内皮生长因子（VEGF）的治疗基因，胶质细胞源性神经营养因子(GDNF)和神经细胞粘附分子(NCAM),使用脐血单核细胞（UCBC）。在这项研究中,SCI后10天将基因工程化的UCBC（200ml盐水中的2×106个细胞）鞘内注射到小型猪中。手术后60天观察对照和实验小型猪。组织学,电生理学,和临床评估表明，在使用基因工程UCBCs治疗的动物中，显着改善。对照和治疗动物的体感诱发电位恢复和组织学发现的差异支持基因细胞收缩对脊髓损伤后恢复的积极作用。这项研究的结果表明，移植UCBCs同时转导三种重组腺病毒Ad5-VEGF，Ad5-GDNF和Ad5-NCAM代表了治疗脊髓损伤的新的潜在成功方法。
