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张燕青,曾园山,曾 湘,丁 英,李 燕.神经营养素-3基因修饰雪旺细胞和神经营养素-3受体基因修饰脊髓间充质干细胞联合移植促进脊髓损伤大鼠神经元存活的研究[J].中国康复医学杂志,2009,24(7):577~581
神经营养素-3基因修饰雪旺细胞和神经营养素-3受体基因修饰脊髓间充质干细胞联合移植促进脊髓损伤大鼠神经元存活的研究    点此下载全文
张燕青  曾园山  曾 湘  丁 英  李 燕
中山大学中山医学院组织胚胎学教研室神经科学研究室,广州 510080
基金项目:国家自然科学基金(30771143);广东省自然科学基金(07117373)
DOI:
摘要点击次数: 2181
全文下载次数: 2020
摘要:
      目的:探讨神经营养素-3 (NT-3) 基因修饰雪旺细胞(SCs)和神经营养素-3受体 (TrkC) 基因修饰骨髓间充质干细胞(MSCs)联合移植对全横断脊髓损伤(SCI)大鼠的大脑皮质感觉运动区、红核和背核受损伤神经元存活的影响,为细胞治疗和基因治疗的临床应用提供依据。方法:将含有NT-3-SCs和TrkC-MSCs的PLGA高分子支架移植到大鼠脊髓全横断损伤处。在术后第67天,取其大脑和脊髓进行冷冻切片。用免疫荧光组织化学染色方法,检测SCI处SCs和MSCs的存活及其外源性基因的表达,并计算大脑皮质感觉运动区内锥体细胞层、中脑红核和L1脊髓背核的神经元数量。结果:2个月后,可见SCI处有移植的SCs和MSCs,其中转染的外源性基因NT-3和TrkC可在移植细胞内表达。NT-3-SCs+TrkC-MSCs移植组大脑皮质感觉运动区内锥体细胞层、中脑红核和L1脊髓背核的神经元数量明显高于其他组。 结论:NT-3基因修饰SCs和TrkC基因修饰MSCs联合移植能够促进全横断SCI大鼠的大脑皮质感觉运动区、中脑红核和脊髓背核受损伤神经元的存活。
关键词:骨髓间充质干细胞  雪旺细胞  神经营养素-3  神经营养素-3受体  脊髓损伤  大脑皮质  红核  背核
The effects of co-transplantation of NT-3 gene modified Schwann cells and TrkC gene modified bone marrow mesenchymal stem cells on the survival of neurons after rat′s spinal cord transection    Download Fulltext
Division of Neuroscience, Dept. of Histology and Embryology, Zhongshan Medical College, Sun Yat- sen University, Guangzhou, 510080
Fund Project:
Abstract:
      Objective:To explore the effects of co-transplantation of neurotrophin-3(NT-3) gene modified Schwann cells (SCs) and NT-3 receptor (TrkC) gene modified bone marrow mesenchymal stem cells (MSCs) on the neuronal survival in internal pyramidal layer of sensorimotor cortex, red nuclei and Clarke′s nuclei after rats′ spinal cord transection, and to provide the instruction for clinical application of cell and gene therapy. Method: The high polymer PLGA scaffolds containing NT-3-SCs and TrkC-MSCs were immediately transplanted into the transected sites of rats′ spinal cord. At the 67th d after operation, brains and spinal cords of rats were removed and sectioned frozenly. The survivals of SCs and MSCs and the expressions of NT-3 and TrkC genes in the injured sites of spinal cord were examined by immunofluorescence histochemistry, and the amounts of neurons in internal pyramidal layer of sensorimotor cortex, red nuclei of brain stem and Clarke′s nuclei of L1 spinal segment were calculated. Result: The transplanted SCs and MSCs could survive, and NT-3 and TrkC could express in transplanted cells after 2 monthes. The amounts of survival neurons in internal pyramidal layer of sensorimotor cortex, red nuclei of midbrain and Clarke′s nuclei of L1 spinal segment in NT-3-SCs+TrkC-MSCs group were move than those in other groups. Conclusion: Co-transplantation of NT-3 genes modified SCs and TrkC genes modified MSCs may promote the survival of neurons of cerebral coxtex, red nuclei and Clarke′s nuclei after rat spinal cord transection.
Keywords:bone marrow mesenchymal stem cells  Schwann cells  neurotrophin-3  neutrophin-3 receptor  spinal cord injury  cerebral cortex  red nuclei  Clarke′s nuclei
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