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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 investigate the role of tacrolimus (FK506) in repair of segmental bone defects by allogeneic mesenchymal stem cells (MSCs) transduced with BMP2 gene by bone marrow-derived bone morphogenetic protein 2 (BMP2) gene. Methods The rat model of femoral segmental bone defects were implanted with different genetically modified MSCs and collagen complexes. Radiological examination was performed at 2, 4, 6, and 8 weeks after operation. The histology Examination and histomorphometric analysis. Results All the MSCs transfected with Adv hBMP 2 (group A) and the allogeneic MSCs transfected with Adv hBMP 2 (group C) were higher than Adv hBMP 2 transfected Of allogeneic MSCs without FK5 0 6 group (D group), the difference was significant (P <0.05). Histological examination showed that in the A and C groups, the lamellar bone was the main bone in group A and group C, while the group B was dominated by the weaved bone and osteoid, with infiltration of inflammatory cells within 8 weeks postoperatively. Histomorphometric analysis showed that after 8 weeks A , While the amount of new bone formation in group C was more than that in group D (P <0.05). Conclusion Short-term low-dose FK506 can inhibit the rejection induced by transplantation of MSCs transfected with Adv hBMP2 gene and promote the repair of long segmental bone defects.