他克莫司促进基因修饰的同种异体间充质干细胞修复骨缺损  

Tacrolimus promoting bone repairing with gene modified allogeneic mesenchymal stem cells

作　　者：朱六龙[1] 汤亭亭[1] 戴戎[1] 郁朝锋[1] 徐小良[1] 楼觉人[2] 

机构地区：[1]上海第二医科大学附属第九人民医院骨科,200011 [2]美国华盛顿大学医学院骨科

出　　处：《中华实验外科杂志》2004年第1期68-70,共3页Chinese Journal of Experimental Surgery

基　　金：上海市科技发展基金资助项目 (1 0JC1 4 0 2 80 1 4 30 70 2 1 )

摘　　要：目的　探讨他克莫司 (FK 5 0 6)在腺病毒介导的转骨形态发生蛋白 2 (BMP 2 )基因的同种异体间充质干细胞 (MSCs)修复节段性骨缺损中的作用。方法　大鼠股骨节段性骨缺损模型 ,分别植入不同的基因修饰的MSCs与胶原复合物 ,于术后 2、4、6、8周行放射学检查 ,术后 8周的标本行组织学检查及组织形态计量学分析。结果　术后 8周 ,放射学评分Adv hBMP 2转染的同系MSCs组 (A组 )、Adv hBMP 2转染的同种异体MSCs应用FK5 0 6组 (C组 )均高于Adv hBMP 2转染的同种异体MSCs未用FK5 0 6组 (D组 ) ,差异有显著性 (P <0 .0 5 )。组织学检查显示 ,术后 8周A、C组以板层骨为主 ,D组以编织骨和类骨质为主 ,内有炎症细胞浸润 ;组织形态计量学分析显示 ,术后 8周A、C组新骨形成的量多于D组 ,差异有显著性 (P <0 .0 5 )。结论　短期小剂量应用FK 5 0 6可抑制Adv hBMP 2基因转染的同种异体大鼠MSCs移植诱发的免疫排斥反应 ,促进长骨干节段性骨缺损的修复。Objective To evaluate the effect of tacrolimus (FK506) on the repair of segmental bone defect of long bone with adenovirus mediated human bone morphogenetic protein-2 gene transferred allogeneic mesenchymal stem cells.Methods Forty-eight male Fischer 344 rats were divided randomly and evenly into 6 groups:Group A:Adv-hBMP-2 transduced syngeneic MSCs;Group B:Adv-βgal transduced syngeneic MSCs;Group C:Adv-hBMP-2 transduced allogeneic MSCs with FK506;Group D:Adv-hBMP-2 transduced allogeneic MSCs without FK506;Group E:Adv-βgal allogeneic transduced MSCs with FK506;Group F:Adv-βgal allogeneic transduced MSCs without FK506.Contracted MSCs collagen mix was implanted in the defect site.Serial radiographs of rat femurs were examined at postoperative 2nd,4th,6th,and 8th week.Harvested specimens at postoperative 8th week underwent histological and histomorphometric analysis.Results The defects in group A,group C and group D had bone formation radiographically at 2nd week postoperatively.The radiographic score of group A and group C was higher than that of group D significantly at postoperative 8th week.Histological analysis demonstrated that the defects in group A and group C were filled with coarsed trabecular bone at postoperative 8th weeks.The defects in the group D were filled with woven bone or preosseous tissue and were infiltrated by inflammatory cells.The other three groups demonstrated little or no bone formation and the defects were filled with connective tissue.Histomorphometric analysis revealed a significantly greater area of bone formation in the defects of group A and group C than in the group D.Conclusion Short-term and low dose of FK506 can suppress immunological rejection evoked by adenovirus mediated bone morphogenetic protein-2 gene transferred allogeneic rat mesenchymal stem cells and increase their capasity to repair segmental bone defect.

关 键 词：他克莫司 基因修饰 同种异体间充质干细胞 修复 骨缺损 

分 类 号：R96[医药卫生—药理学]