目的观察树突细胞(dendritic cells,DCs)及神经干细胞/前体细胞(neural stem/progenitor cells,NSPCs)联合移植对大鼠脊髓损伤(spinal cord injury,SCI)修复的作用,并初步探讨其机制。方法 SD成年大鼠80只制作脊髓损伤模型,随机数字表法分为4组,SCI 9 d后分别移植Hanks平衡盐溶液(Hanks balanced salt solution,HBSS)、DCs、NSPCs、DCs+NSPCs。通过BBB评分法评估SCI大鼠运动功能,组织病理学方法观察损伤局部病理学改变。采用增强型绿色荧光蛋白(enhanced green fluorescence protein,EGFP)转基因SD大鼠脑来源的NSPCs,损伤局部移植2周后观察存活情况。免疫组织荧光法观察损伤局部神经生长因子-3(neurotrophin-3,NT-3)的表达变化。结果移植84 d后DCs+NSPCs组运动功能明显改善(P〈0.05),DCs+NSPCs组、NSPCs组、DCs组、HBSS组BBB评分分别为(11.70±0.99)、(9.75±0.50)、(7.40±0.93)、(5.93±0.78),相邻两组有统计学差异(P〈0.05)。DCs+NSPCs组损伤区范围及空洞均明显减少(P〈0.05),NSPCs存活数量明显增加(P〈0.01),显著上调损伤区NT-3的表达。结论 DCs联合NSPCs移植能够促进神经干细胞存活,减少损伤区范围及空洞形成,改善SCI大鼠运动功能。损伤区NT-3的表达增加可能是促进修复的机制之一。
Objective To study the effect and mechanism of co-transplantation of neural stem/progenitor cells(NSPCs) with dendritic cells(DCs) on spinal cord injury(SCI) in adult rats.Methods Eighty adult SD rats were subjected to moderate SCI.Nine days after SCI,SD rats were randomly divided into 4 groups and locally injected with Hanks' balanced salt solution(HBSS),DCs,NSPCs,and DCs+NSPCs.The motor functions of rats after SCI were evaluated with BBB scores.The local pathological changes of injured sites were observed by histopathological means.NSPCs from brain of enhanced green fluorescence protein(EGFP) transgenic rat or common newborn rat were transplanted,and NSPCs survival was studied two weeks later.Neurotrophin-3(NT-3) expression in injured sites was detected by immunofluorescence to illustrate the underlying mechanism.Results Eighty-four days after treatment,the DCs+NSPCs group exhibited significantly better motor function than other groups(P0.05),with BBB scores: DCs+NSPCs group 11.70±0.99,NSPCs group 9.75±0.50,DCs group 7.40±0.93 and HBSS group 5.93±0.78.The cavities and scars in the DCs+NSPCs group were smaller than those in other groups(P0.05).In the DCs+NSPCs group,increased neurotrophin-3(NT-3) expression(compared with other groups,P0.05) and improved NSPCs survival(compared with NSPCs group,P0.01) were observed in the injured sites.Conclusion Co-transplantation of NSPCs with DCs promotes NSPCs survival and functional recovery in adult rats after SCI,possibly involving NT-3 up-regulation in injured sites.