过表达NT-3 SCs和过表达TrkC NSCs移植减少脊髓损伤处瘢痕形成和促进神经再生  

Transplantation of Schwann cells overexpressed NT-3 and neural stem cells overexpressed TrkC may reduce the scar formation and promote the nerve regeneration in the injured site of spinal cored

作　　者：王俊梅[1] 曾园山[1] 

机构地区：[1]中山大学中山医学院组织胚胎学教研室,广东广州510080

出　　处：《解剖学研究》2011年第5期367-372,共6页Anatomy Research

基　　金：国家自然科学基金(30270700);广东省社会发展攻关基金(2003C33808)

摘　　要：目的探讨神经营养素-3(NT-3)基因修饰雪旺细胞(SCs)和NT-3受体(TrkC)基因修饰神经干细胞(NSCs)联合移植能否减少大鼠脊髓全横断损伤处的瘢痕组织,并促进下行神经纤维再生。方法用NT-3基因的重组腺病毒(Ad-NT-3)感染培养的SCs(NT-3-SCs),同时用含TrkC基因的重组腺病毒(Ad-TrkC)感染培养的NSCs(TrkC-NSCs)。此外,还将Ad-LacZ分别感染SCs和NSCs。然后建立大鼠脊髓全横断损伤模型,将NT-3-SCs+TrkC-NSCs联合移植到损伤处。所有动物存活60 d后,在脊髓横断处远端3 mm组织内注射荧光金(FG),动物再存活7 d。最后灌注固定动物、取材和切片,并行形态学观察。结果①在移植组中,脊髓横断处头侧端、中脑红核及大脑体感运动区皮质内锥体细胞层有少量FG标记神经元。②在脊髓损伤区内,细胞移植组比对照组的纤维粘连蛋白(FN)阳性细胞减少,S-100阳性细胞增多。③电镜下可见,细胞移植组的脊髓损伤区内成纤维细胞和胶原纤维减少。结论 NT-3基因修饰SCs和TrkC基因修饰NSCs联合移植能够减少大鼠脊髓全横断损伤处的瘢痕组织,促进下行神经纤维的再生。Objective To study whether co-transplantion of NT-3 gene modified SCs and TrkC gene modified NSCs could reduce the formation of scar tissue and promote the regeneration of descending nerve fibers in the lesion of spinal cord.Methods SCs（NT-3-SCs） were infected by recombinant adenovirus vector carrying NT-3 gene（Ad-NT-3）.In the meanwhile,NSCs（TrkC-NSCs） were infected by recombinant adenovirus vector carrying TrkC gene（Ad-TrkC）.Some SCs and NSCs were respectively infected by recombinant adenovirus vector carrying LacZ gene（Ad-LacZ）.Then the model of completely transected spinal cord injury was established in adult Sprague-Dawley rats.NT-3-SCs＋TrkC-NSCs were grafted into the transected site of spinal cord.60 days after the transplantation,fluorogold（FG） was injected into the spinal cord 3 mm caudal to the transected site.7 days after injected FG,animals were then sacrificed and fixed.Section and morphological serial studies were performed.Results ①In the transplant group,there were some FG-labeled neurons in the rostral spinal cord nearby the transected site,the red nuclei and the internal pyramidal layer of sensorimotor cortex.②In the cell tranplant group there are less fibronection positive cells and more S-100 positive cells than control group.③Electron microscope showed the less fibroblast and collagenous fibre bundlec in injured spinal cord in the grafted cells groups.Conclusion Co-transplantation of NT-3 gene modified SCs and TrkC gene modified NSCs may reduce the formation of scar tissue and promote the regeneration of descending nerve fibers in the lesion of spinal cord.

关 键 词：神经营养素-3 TRKC 重组腺病毒 神经干细胞 雪旺细胞 基因治疗 脊髓损伤 神经纤维再生 

分 类 号：R651.2[医药卫生—外科学]