携带胶质细胞源性神经营养因子基因的骨髓间充质干细胞移植对兔坐骨神经缺损的治疗作用

目的 探讨胶质细胞源性神经营养因子(GDNF)局部长期高表达对坐骨神经缺损的治疗作用.方法 实验组以骨髓间充质干细胞(MSCs)作为种子细胞,以慢病毒介导的GDNF转染骨髓间充质干细胞后,结合细胞外基质凝胶构建神经移植复合体共同移植入兔20 mm坐骨神经缺损处.以绿色荧光蛋白(GFP)基因作为报告基因.同时设基质凝胶对照组和基质凝胶+MSCs对照组,每组10只.结果 实验组部分兔坐骨神经连续性完全恢复,而两对照组坐骨神经连续性均未完全恢复.转染GDNF基因的MSC迁移距离可达20 mm,提示该移植细胞与宿主细胞具有较好的整合作用,且实验组绿色荧光蛋白(GFP)+胶质纤维酸性蛋白抗体(GFAP)、GFP+S100双标细胞占GFP阳性细胞的百分比分别高达70%和60%,而基质凝胶+MSCs对照组以上两种阳性细胞的百分比为40%和30%.结论 移植的基因工程MSCs能够明显促进损伤坐骨神经的再生,GDNF可能促进了MSCs向雪旺细胞样细胞分化.

Repair of sciatic nerve defect with implantation of glial cell line-derived neurotrophic factor locally secreting mesenchymal stem cells in rabbits

Objective To investigate the repairative effect of local high expression of glial cell line-derived neurotrophic factor (GDNF) in the repair of sciatic nerve defects. Green fluorescent protein (GFP) gene was used as reporter gene. Two groups including gel matrix control group and gel matrix plus MSCs group were set ( 10 rabbits per group). Methods GDNF secreting mesenchymal stem cells (MSCs) mediated by lentiviral vectors were suspended in Matrigel to produce the artificial graft, and then it was locally implanted to a 20 mm-long sciatic nerve defect in rabbits. Results In the GDNF group,the nerve continuity was restored in seven rabbits and the functional amelioration of the wounded limb was apparent. While there found no restoration of the nerve continuity in the control groups. The migration distance of GDNF secreting MSCs was 20 mm, suggesting a good integration of the transplanted cells with host cells. The glial fibrillary acidic protein (GFAP) + green fluorescent protein (GFP) and -100 protein GFP accounted for 60% and 70% respectively in the experimental group, while it was only 40% and 30% in gel matrix plus MSCs group. Conclusions Local implantation of GDNF secreting MSCs can promote the regeneration and functional recovery of the sciatic nerves. GDNF seems to play an important role in inducing transdifferentiation of MSCs to Schwann cell lineage.