胶原/硫酸肝素支架联合神经干细胞促进脊髓损伤后运动功能的恢复  

Collagen/heparin sulfate scaffold combined with neural stem cells promote motor function recovery after spinal cord injury

作　　者：曹宗锐[1] 郑博 钟琳 胡良聪 张秀莉 屈波 蒋涛[1] Cao Zongrui;Zheng Bo;Zhong Lin;Hu Liangcong;Zhang Xiuli;Qu bo;Jiang Tao(Department of Orthopedics,First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,Sichuan Province,China;Second Affiliated Hospital of Kunming Medical University,Kunming 650101,Yunan Province,China;Department of Orthopedics,Affiliated Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,Hubei Province,China)

机构地区：[1]成都医学院第一附属医院骨科,四川省成都市610500 [2]昆明医科大学第二附属医院,云南省昆明市650101 [3]华中科技大学同济医学院附属协和医院骨科,湖北省武汉市430022

出　　处：《中国组织工程研究》2019年第34期5454-5461,共8页Chinese Journal of Tissue Engineering Research

基　　金：四川省教育厅支撑项目(15AZ0265)，项目名称：老年男性髋部骨折患者血清睾酮水平与骨质疏松、骨折风险的相关性，项目负责人：蒋涛~~

摘　　要：背景:近些年来,胶原/硫酸肝素支架作为神经组织工程支架已被用于周围神经、脊髓和脑损伤的修复中。目的:观察胶原/硫酸肝素支架联合神经干细胞移植对脊髓损伤后运动功能恢复的影响。方法:将SD乳鼠神经干细胞接种于胶原/硫酸肝素支架上培养7 d,构建细胞-支架复合物。将60只成年雌性SD大鼠(购自成都达硕生物科技有限公司)随机分为4组,每组15只:假手术组仅切除T10椎板,模型组切除T10处1.5 mm脊髓建立脊髓损伤模型,支架组建立脊髓损伤模型后植入胶原/硫酸肝素支架,细胞-支架组建立脊髓损伤模型后植入细胞-支架复合物。术后1,2,3,4,6,8周进行BBB评分与斜板实验,观察大鼠肢体功能恢复;术后8周检测大鼠双后肢运动诱发电位,观察运动功能恢复情况;术后8周对脊髓损伤处进行核磁扫描,获得弥散张量成像图像,观察神经纤维再生情况。实验获得成都医学院第一附属医院伦理委员会批准。结果与结论:①术后2,3,4,6,8周,细胞-支架组的BBB评分、斜板实验角度均高于模型组、支架组(P<0.05,P<0.01);②细胞-支架组大鼠双侧后肢的运动诱发电位振幅高于模型组、支架组(P<0.05,P<0.01),潜伏期短于模型组、支架组(P<0.05,P<0.01);③弥散张量成像显示,假手术组神经纤维完整,模型组病变部位周围神经纤维缺乏不同方向的连续性,支架组、细胞-支架组可见较多数量的神经纤维穿过损伤区域,并且细胞-支架组穿过损伤区域的神经纤维数量更多;④结果表明,胶原/硫酸肝素支架联合神经干细胞可促进大鼠脊髓损伤处神经纤维的再生,改善大鼠双侧后肢运动功能。BACKGROUND:In recent years,collagen/heparin sulfate scaffolds have been used as nerve tissue engineering scaffolds in the repair of peripheral nerves,spinal cords,and brain injury.OBJECTIVE:To investigate the effects of collagen/heparin sulfate scaffold combined with neural stem cells on motor function recovery after spinal cord injury.METHODS:Sprague-Dawley rat neural stem cells were inoculated on a collagen/heparin sulfate scaffold for 7 days to construct a cell-scaffold complex.Sixty adult female Sprague-Dawley rats(purchased from Chengdu Dashuo Biotechnology Co.,Ltd.,China)were randomly divided into four groups with 15 rats in each group.In the sham operation group,only T10 lamina was removed.In the model group,rat models of spinal cord injury were stablished by removing 1.5 mm long spinal cord at the level of T10 lamina.In the scaffold group,collagen/heparin sulfate scaffolds were implanted in the spinal cord injury sites.In the cell-scaffold complex group,collagen/heparin sulfate scaffold-neural stem cells complex was implanted into the injury site.At postoperative 1,2,3,4,6 and 8 weeks,BBB score and oblique plate test were performed to evaluate the recovery of limb function in rats.At postoperative 8 weeks,the motor evoked potentials of rat hind limbs were detected and the recovery of motor function was evaluated.At postoperative 8 weeks,a nuclear magnetic scan was performed on the spinal cord injury site,and a diffusion tensor imaging image was obtained to observe nerve fiber regeneration.This study was approved by the Ethics Committee of the First Affiliated Hospital of Chengdu Medical College,China.RESULTS AND CONCLUSION:At postoperative 2,3,4,6 and 8 weeks,the BBB score and oblique plate test angle in the cell-scaffold complex group were significantly greater than those in the model and scaffold groups(P<0.05,P<0.01).The amplitude of motor evoked potential in the rat hind limbs in the cell-scaffold group was significantly higher than that in the model and scaffold groups(P<0.05,P<0.01).The latency in t

关 键 词：脊髓损伤 胶原 硫酸肝素 胶原/硫酸肝素支架 支架 神经干细胞 神经再生 功能恢复 弥散张量纤维束成像 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学]