骨髓间充质干细胞移植治疗失神经肌萎缩

Transplantation of bone marrow mesenchymal stem cells for denervated muscular atrophy

背景:外科显微镜手术和一些辅助治疗方法均无法通过修复损伤的神经细胞来有效延缓或治疗失神经肌萎缩。研究发现骨髓间充质干细胞具有定向分化潜能,并且在一定环境因素下能对损伤的组织进行修复,由此推测其可以对失神经萎缩肌肉起到一定的修复作用。目的:探讨移植骨髓间充质干细胞是否能够减轻和延缓失神经肌肉组织萎缩。方法:分离培养SD大鼠骨髓间充质干细胞,取第3代骨髓间充质干细胞经BrdU标记后用于移植治疗。将30只SD大鼠分为3组,每组10只,对每只大鼠左后肢进行手术。假手术组只暴露坐骨神经主干,不钳夹神经,移植治疗组、模型对照组钳夹坐骨神经主干后,向其支配的腓肠肌注射骨髓间充质干细胞悬液和不含胎牛血清的DMEM培养液。骨髓间充质干细胞移植后1,2周,采用BBB评分评价各组大鼠左后肢运动功能;骨髓间充质干细胞移植后14 d,取腓肠肌组织进行苏木精-伊红染色和BrdU免疫组化染色。结果与结论:第3代骨髓间充质干细胞BrdU标记为阳性;标记的骨髓间充质干细胞能在移植治疗组失神经损伤的肌肉组织中存活并起修复作用;相对于模型对照组,移植治疗组失神经肌纤维由相互融合重新恢复规整。结果表明移植骨髓间充质干细胞能够减轻和延缓失神经肌肉组织萎缩。

BACKGROUND:Microscopic surgery or some adjuvant treatments can neither effectively delay nor treat denervated muscle atrophy by repairing damaged nerve cells.Studies have found that bone marrow mesenchymal stem cells have the potential for directional differentiation and repair damaged tissues under certain environmental factors.It is speculated that the cells can play a certain role in repairing denervated atrophic muscles.OBJECTIVE:To investigate whether transplantation of bone marrow mesenchymal stem cells can alleviate and retard atrophy of denervated muscles.METHODS:Primary bone marrow mesenchymal stem cells were isolated from Sprague-Dawley rats,and passage 3 cells were labeled by BrdU for cell transplantation.Thirty Sprague-Dawley rats were divided into three groups,10 rats in each group.In the sham operation group,only the main trunk of the sciatic nerve was exposed but not clamped.In the treatment group,the main trunk of the sciatic nerve was clamped and bone marrow mesenchymal stem cell suspension was injected into the gastrocnemius muscle.In the control group,after the sciatic nerve trunk was clamped,the gastrocnemius muscle innervated by the sciatic nerve was injected with DMEM medium of equal volume(without cells and fetal bovine serum).Basso,Beattie and Bresnahan scores were used to evaluate the motor function of the rat’s left hindlimb at 1 and 2 weeks after cell transplantation.Changes in the gastrocnemius muscle fibers were observed by hematoxylin-eosin staining and BrdU immunohistochemical staining at 14 days after cell transplantation.RESULTS AND CONCLUSION:The passage 3 bone marrow mesenchymal stem cells were positive for BrdU.The labeled cells could survive in and repair the denervated muscle tissue in the treatment group.Compared with the model group,the denervated muscle fibers of the treatment group recovered from mutual fusion and re-arranged regularly.To conclude,transplantation of bone marrow mesenchymal stem cells can alleviate and retard atrophy of denervated muscles.