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CXCR4基因转染间充质干细胞防治椎间盘退变的疗效观察
作者:韦继南1 2  蔡峰2  吴小涛1  王锋2  洪鑫1  王运涛1  汤文浩1 
单位:1. 东南大学 附属中大医院, 江苏 南京 210009;
2. 东南大学 医学院, 江苏 南京 210009
关键词:间充质干细胞 趋化因子受体4 椎间盘 治疗  
分类号:R681.53;R329.2
出版年·卷·期(页码):2015·34·第四期(541-546)
摘要:

目的:初步探讨高表达CXCR4的间充质干细胞防治椎间盘退变的疗效。方法:通过慢病毒载体转染系统将CXCR4基因转染间充质干细胞,使后者过表达CXCR4。将15只新西兰大白兔椎间盘穿刺制造退变模型后随即行细胞移植治疗,实验分为CXCR4-MSCs、MSCs和PBS组(对照组),每组5只,术后4、8周从椎间盘高度、组织学、2型胶原mRNA及Aggrecan mRNA含量改变方面观察其疗效并进行分析。结果:基因转染后Western blot证实干细胞高表达CXCR4,转染成功。移植术后4周3组的椎间盘高度均较移植前明显下降,证实造模成功,3组之间差异无统计学意义;术后8周CXCR4-MSCs组椎间盘高度降低不明显,而MSCs组及PBS组显著降低,PBS组更为显著,差异有统计学意义。移植后4、8周,组织学可见CXCR4-MSCs组和MSCs组椎间盘退变显著减慢,表现出一定的延缓退变作用。RT-PCR结果表明,术后8周Aggrecan mRNA及2型胶原mRNA均有表达,其中CXCR4-MSCs组较MSCs组和PBS组Aggrecan mRNA表达明显增多,差异具有统计学意义;3组间2型胶原mRNA表达差异无统计学意义。结论:CXCR4基因转染成功,CXCR4-MSCs能明显延缓椎间盘退变。

Objective: To explore the role of high expression of CXCR4 mesenchymal stem cells(MSCs) during degeneration of intervertebral disc. Methods: Recombinant lentiviral vector transduction was carried out to over-express CXCR4 in MSCs. Cell transplantations were followed immediately by puncturing to create degeneration model. 15 New Zealand white rabbits were divided into three groups:CXCR4-MSCs groups, MSCs groups and PBS groups. Disc height Index, histological section HE stain and mRNA of Aggrecan and type Ⅱ collagen were obtained at 4 and 8 weeks after transplantations. Results: MSCs were efficiently over-expressed CXCR4 and verified by Western blot. 4 weeks after transplantations, the disc height of three groups decreased significantly than pre-operation. There were no significant differences among the three groups. There was no obvious decrease of disc height in CXCR4-MSCs group at 8 weeks after transplantations. But there were significantly decreases in MSCs groups and PBS groups. There were significant differences among three groups at 8 weeks. Disc degenerations in histology significantly slowed down in CXCR4-MSCs group and MSCs group at 4 and 8 weeks after transplantations rather than PBS group. RT-PCR results showed that Aggrecan mRNA and type Ⅱ collagen mRNA were both expressed at 8 weeks after transplantations. Aggrecan mRNA expression of CXCR4-MSCs group was more than that of MSCs group and PBS group, respectively, there was significant difference. Type Ⅱ collagen mRNA expressions of three groups had no significant differences. Conclusion: CXCR4 gene can be successfully transfected to MSCs. CXCR4-MSCs transplantation can significantly slow down intervertebral disc degeneration.

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