CXCL12/CXCR4生物学轴对骨髓间充质干细胞修复脊髓损伤的影响

CXCL12/CXCR4 biology axis effects on the repair of spinal cord injury with bone marrow mesenchymal stem cells

背景:研究发现不同途径移植骨髓间充质干细胞均能向脊髓损伤部位迁移,进而发挥治疗作用。目的:探讨CXCL12/CXCR4生物学轴对骨髓间充质干细胞趋向脊髓损伤部位迁移的作用。方法:采用改进的脊椎骨破坏法制备脊髓损伤模型。假手术组只打开皮肤,不损伤脊髓且不作任何干预;模型组于造模后第2天采用腰骶鞘内注射5μL生理盐水;细胞移植组于造模后第2天采用腰骶鞘内移植5μL骨髓间充质干细胞。结果与结论:①荧光显微镜下可见,横切的脊髓损伤局部有大量的标记细胞聚集,而在损伤部位远端1cm处,仅见少量的标记骨髓间充质干细胞。②骨髓间充质干细胞表达中等水平的趋化因子CXCL12,其特异性结合受体CXCR4也有低水平表达。③脊髓损伤7d后,局部CXCL12表达增强,主要集中在脊髓损伤部位的皮质区域,而在损伤部位1cm以外的脊髓组织未见大量表达的CXCL12。CXCR4蛋白表达没有明显的时间效应。④检测CXCL12mRNA的转录水平发现细胞移植组的CXCR4转录水平明显高于假手术组和模型组,损伤后14d脊髓损伤局部CXCL12的转录水平最强,21d时降低,CXCL12的局部转录水平明显高于远端。⑤脊髓损伤部位也表达趋化因子CXCR4,但其表达水平没有时程差异。损伤局部的CXCR4转录水平略高于远端,但差异无显著性意义。说明CXCL12/CXCR4生物学轴参与骨髓间充质干细胞向脊髓损伤区域迁移。

BACKGROUND：The research discovered that bone marrow mesenchymal stem cells（BMSCs） through different approaches can migrate to the injured site of the spinal cord,and play curative effects.OBJECTIVE：To discuss the role of CXCL12/CXCR4 biology axis on the migration of BMSCs into the injured site after spinal cord injury（SCI）.METHODS：SCI models were prepared using modified spinal damage method.There was no intervention in the sham operation group beside skin open.In the model group,lumbar intrathecal injection of 5 μL normal saline was used at 2 days after modeling;in the transplantation group,lumbar intrathecal injection of 5μL BMSCs was administrated at 2 days after modeling.RESULTS AND CONCLUSION：Under the fluorescence microscope,a large mass of labeled cells gathered at the injured site,however,only a few of labeled BMSCs could be seen 1 cm distant from the distal injured site.BMSCs expressed the medium level of CXCL12,and CXCR4 also had a low level expression in the BMSCs.Seven days after SCI,partial CXCL12 expression strengthened,mainly in the cortex region of SCI,but there were no massive expressions of CXCL12 1 cm outside the injured site.CXCR4 protein expression did not present with a time-effect manner.CXCR4 transcriptional level in the transplantation group was obviously higher than that in the sham operation group and model group.At 14 days after SCI,CXCL12 transcriptional level reached the peak,and lowered at 21 days.The local CXCL12 transcriptional level was remarkably higher than that at the distal end.CXCR4 also expressed at the injured site in a time-independent manner.The partial CXCR4 transcriptional level was slightly higher than that at the distal end,but there was no significant difference.The results indicated that the CXCL12/CXCR4 biology axis participates in the migration of BMSCs into the injured zone after SCI.