神经营养素-3基因修饰嗅鞘细胞移植对急性脊髓损伤作用的实验研究

A study of intraspinal implantation of neurotrophin-3 modified olfactory ensheathing glia in rats with acute spinal cord injury

目的:观察神经营养素-3(NT-3)基因转染嗅鞘细胞(OEG)移植对急性大鼠脊髓损伤的作用。方法:将自行构建的质粒pEGFP-NT3应用脂质体介导的方法导入体外培养的嗅鞘细胞,并移植入急性脊髓损伤大鼠体内,连续观察12周,与接受单纯OEG、空白质粒转染OEG移植的脊髓损伤大鼠进行比较。结果:移植转染pEGFP-NT3后的OEG能在体内长期存活,表达NT-3基因,与对照组比较能更好地促进脊髓损伤区轴突的再生和后肢功能的恢复。结论:OEG是脊髓损伤基因治疗较好的受体细胞。转染NT-3基因的OEG移植后可以在体内较长时间存活,能明显促进急性脊髓损伤神经纤维的再生和功能恢复,为基因修饰嗅鞘细胞在脊髓损伤治疗中的应用提供了实验和理论依据。

Objective：To observe the therapeutic effect of olfactory ensheathing glia（OEG） transfected with neurotrophin-3 （NT-3） gene in rats with thoracic spinal cord injury.Method：Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pEGFP-NT3 and subsequently implanted into adult Wistar rats directly after contusion of the thoracic spinal cord （Tg）.Implanted animals were subjected to transfection with pEGFP-NT3,pEGFP alone,or no plasmid, respectively.Result： At 3 months after transplantation, all OEG grafts were filled with neurofilament-positive axons,and cationic liposome-modiated expression of NT-3 by implanted cells significantly enhanced regenerative axonal sprouting.Behavioral analysis revealed that recovery of hind limb function improved after implantation of OEG transfected with a NT-3-encoding plasmid vector.Conclusion：OEG may be a good candidate for neurotrophic factor delivery.Genetic engineered OEG not only resulted in cells that were more effective in promoting axonal outgrowth but also can enhance recovery of neurological function after spinal cord injury.