他克莫司与肌源性干细胞联合应用对去细胞异体神经支架移植后神经再生和修复作用的影响  

Co-application of muscle-derived stem cells and FK-506 influences nerve regeneration and recovery following acellular nerve allograft implantation

作　　者：连霄飞[1] 王伟[2] 张力[2] 张万里[1] 刘新胜[1] 王程越[2] 

机构地区：[1]辽宁医学院,辽宁省锦州市121001 [2]锦州市中心医院,辽宁省锦州市121013

出　　处：《中国组织工程研究与临床康复》2010年第3期389-392,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:肌源性干细胞作为种子细胞用于制备组织工程化人工神经已经被越来越多的学者所接受。他克莫司不仅具有抗免疫排斥的效果,还具有强大的促进神经再生和修复的作用。那么能否将两项因素与去细胞异体神经支架形成一个桥接体,既能抑制异体移植的免疫反应,又能有效促进损伤神经的再生与修复?目的:采用理化联合处理方法制备去细胞异体神经支架,探讨肌源性干细胞与免疫抑制剂他克莫司联合应用对去细胞异体神经支架移植后神经再生及功能恢复的影响。方法:SD大鼠坐骨神经经脱细胞处理后形成异体神经桥接体。用100μL微量注射器将含他克莫司与肌源性干细胞的凝胶注入异体神经支架,用以修复大鼠的坐骨神经缺损。32只成年SD大鼠,随机分为4组,每组8只。切断其左侧坐骨神经造成10mm的缺损。他克莫司+肌源性干细胞组、肌源性干细胞组、他克莫司组以注射植入后的异体神经进行桥接;对照组仅注入透明质酸凝胶。术后8,12周进行坐骨神经指数和神经电生理测定。术后12周进行大体观察,神经组织学和超微结构观察。结果和结论:在同一时点他克莫司+肌源性干细胞组坐骨神经功能指数、坐骨神经运动传导速度恢复率、移植体及远段有髓纤维计数均优于其他3组(P<0.05)。各组神经移植体粗细基本正常,表面大量血管分布,与周围组织轻度粘连;他克莫司+肌源性干细胞组较其他3组再生神经纤维更加密集、排列规则整齐;移植体许旺细胞大量增殖,移植体中央及远段内的有髓神经纤维密度、直径高于肌源性干细胞组、他克莫司组,微束之间结缔组织少,接近于正常。说明肌源性干细胞和他克莫司联合应用促进去细胞异种神经移植的神经再生与功能恢复的效果优于单独应用。肌源性干细胞和他克莫司在周围神经损伤修复中是一对具有协同作用的因子�BACKGROUND：Muscle-derived stem cells（MDSCs） have been accepted as seeding cells in tissue engineered artificial nerves.Tacrolimus exhibits anti-immunologic rejection and promotes nerve regeneration and recovery.Whether can combine these factors with acellular nerve to form a new bridge that can inhibit immunologic rejection and promote nerve regeneration is uncertain.OBJECTIVE：Using the freeze-thawing combined optimized acellular nerve hypotonic-chemical detergent to prepare acellular nerveallograft scaffold.To explore the effect of co-application of MDSCs and FK-506 on nerve regeneration and function recovery following acellular nerve allograft implantation.METHODS：The sciatic nerve derived from SD rats was prepared nerve bridge after acellular disposal.Gel containing FK-506 and MDSCs was injected into acellular nerveallograft scaffold with 100 μL microsyringe to repair defects.A total of 32 SD rats were randomly divided into 4 groups,with 8 animals in each group.A gap of 10 mm of left sciatic nerve was removed.And then the defects were repaired by extracted nerve graft containing FK-506＋MDSCs,MDSCs and FK-506,respectively.In the control group,only hyaluronic acid gel was injected.Sciatic nerve function index（SFI） and electrophysiological exam were performed at weeks 8 and 12 after operation.Gross observation,neurohistological and ultrastructure were observed at week 12 after operation.RESULTS AND CONCLUSION：Compared with the same time point,the SFI,recovery rate of the motor nerve conduction velocities（MNCV）,and myelinated nerve fibers in grafting part and in its distal part in the FK-506＋MDSCs group were superior to other groups（P0.05）.The nerve grafts were in normal size with considerable blood vessels and slightly connected to peripheral tissues.Compared to other groups,the regenerated nerve fiber in the FK-506＋MDSCs group was more density with well-arranged order.A great quantity of Schwann cells proliferated in grafting.The density and diameter of myelinated fiber in the midd

关 键 词：周围神经损伤 异体神经移植 神经再生 肌源性干细胞 他克莫司 

分 类 号：R318[医药卫生—生物医学工程]