中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (24): 2189-2196.doi: 10.4103/1673-5374.147952

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

亚低温联合NgR沉默神经干细胞/许旺细胞构建细胞支架移植修复脊髓损伤

  

  • 收稿日期:2014-11-25 出版日期:2014-12-25 发布日期:2014-12-25

Mild hypothermia combined with a scaffold of NgR-silenced neural stem cells/Schwann cells to treat spinal cord injury

Dong Wang 1, Jinhua Liang 2, Jianjun Zhang 1, Shuhong Liu 3, Wenwen Sun 1   

  1. 1 Department of Neurosurgery, the Fourth Center Clinical College of Tianjin Medical University, Tianjin Fourth Central Hospital, Tianjin, China
    2 Department of Clinical Detection, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang Province, China
    3 Department of Epidemiology, Logistics University of People’s Armed Police Force, Tianjin, China
  • Received:2014-11-25 Online:2014-12-25 Published:2014-12-25
  • Contact: Wenwen Sun, Department of Neurosurgery, the Fourth Center Clinical College of Tianjin Medical University, Tianjin Fourth Central Hospital, Tianjin 300140, China, wd5609@hotmail.com.
  • Supported by:

    This study was supported by a grant from the Application Basis and Front Technology Projects of Tianjin (Science and Technology Foundation of Tianjin), No. 12JCYBJC18000.

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摘要：

由于抑制Nogo可促进突起生长和神经细胞分化，因此以Nogo受体NgR基因沉默的神经干细胞/许旺细胞建立的细胞支架可能改善脊髓损伤的微环境。而既往研究也显示亚低温有效减轻脊髓二次损伤，可产生神经保护作用。实验旨在观察NgR基因沉默神经干细胞/许旺细胞与聚乳酸-羟基乙酸共聚物支架移植联合亚低温修复大鼠脊髓T9节段半横断损伤的效果。与单纯聚乳酸-羟基乙酸支架移植及神经干细胞和许旺细胞复合聚乳酸-羟基乙酸共聚物支架移植相比，亚低温（34℃，6h）结合NgR沉默细胞支架移植治疗的脊髓损伤大鼠后肢运动功能和后肢神经电生理功能明显改善，且损伤脊髓病理变化减轻，移植存活细胞和神经纤维数量增加，且脊髓病理损伤情况及移植存活细胞和神经纤维数量优于未进行亚低温治疗的大鼠。说明亚低温联合NgR基因沉默组织工程支架有潜力用于修复脊髓损伤。

关键词: 神经再生, 脊髓损伤, 神经干细胞, 许旺细胞, 亚低温, 细胞支架, 聚乳酸-羟基乙酸共聚物, 神经功能

Abstract:

Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were clearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold + mild hypothermia at 34°C for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.

Key words: nerve regeneration, spinal cord injury, neural stem cells, Schwann cells, mild hypothermia, cell scaffold, poly(D,L-lactide-co-glycolic acid), neurological function, neural regeneration