中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (8): 677-685.doi: 10.3969/j.issn.1673-5374.2013.08.001

• 原著:脊髓损伤修复保护与再生 •    下一篇

NgR基因沉默细胞与复合支架移植治疗脊髓损伤

  

  • 收稿日期:2012-08-04 修回日期:2013-01-07 出版日期:2013-03-15 发布日期:2013-03-15
  • 基金资助:

    天津市卫生局科技基金(No. 2010ky04)；天津市科技基金(No. 12JCYBJC18000)

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Dong Wang1, Yuhong Fan2, Jianjun Zhang1   

  1. 1 Department of Neurosurgery, Tianjin Fourth Central Hospital, Tianjin 300140, China
    2 Department of Stomatology, First Clinical College, Hebei North University, Zhangjiakou 075000, Hebei Province, China
  • Received:2012-08-04 Revised:2013-01-07 Online:2013-03-15 Published:2013-03-15
  • Contact: Dong Wang★, Master, Associate chief physician. Department of Neurosurgery, Tianjin Fourth Central Hospital, Tianjin 300140, China, wd5609@hotmail.com.
  • Supported by:

    This study was sponsored by the Science and Technology Foundation of Tianjin Health Bureau, No. 2010ky04 and the Application Basis and Front Technology Projects of Tianjin (Science and Technology Foundation of Tianjin), No. 12JCYBJC18000.

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摘要：

NgR基因可使骨髓间充质干细胞移植后的神经元再生受到抑制。聚乳酸-乙醇酸支架具备良好的组织相容性，可促进再生神经纤维有序生长。实验利用siRNA抑制骨髓间充质干细胞和许旺细胞中NgR基因的表达，并联合聚乳酸-乙醇酸支架，移植于脊髓损伤模型大鼠的脊髓组织损伤区，同时设立单纯支架组作对照。苏木精伊红染色和免疫组化染色显示，相比单纯支架组，移植4周后，NgR基因沉默细胞联合支架移植的大鼠后肢运动功能较好，脊髓组织中骨髓间充质干细胞数量及神经元样细胞均增多。HRP示踪结果显示，移植8周后，透射电镜下显示，大鼠脊髓横断面出现新生的无髓及有髓HRP阳性神经纤维和完整的再生轴突髓鞘。结果说明应用NgR基因沉默骨髓间充质干细胞和许旺细胞并联合聚乳酸-乙醇酸支架移植,能够明显促进脊髓损伤大鼠的脊髓神经元轴突再生，并改善肢体的功能。

关键词: 神经再生, 脊髓损伤, 骨髓间充质干细胞, 许旺细胞, 聚乳酸-乙醇酸, NgR基因, 大鼠, 基因沉默, 轴突, 神经元, 基金资助文章, 图片文章

Abstract:

Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.

Key words: neural regeneration, spinal cord injury, bone marrow mesenchymal stem cells, Schwann cells, poly(D,L-lactide-co-glycolic acid), Nogo-66 receptor gene, rats, gene silencing, grants-supported paper, photographs-containing paper, neuroregeneration