杆状病毒修饰后的脂肪干细胞移植治疗mdx鼠的实验研究  

The Study of Baculovirus Modified Adipose-derived Stem Cells Tranplantation on mdx Mice

作　　者：孔杰[1,2] 操基清[1] 陈菲[1] 杨娟[1] 张成[1] 

机构地区：[1]中山大学第一附属医院,510080 [2]广州中医药大学附属宝安区中医院,518133

出　　处：《中国临床神经科学》2015年第4期391-398,共8页Chinese Journal of Clinical Neurosciences

摘　　要：目的利用经杆状病毒基因载体系统进行micro-dystrophin基因修饰后的脂肪干细胞(ADSCs)移植治疗Duchenne型肌营养不良症模型(mdx)鼠,探讨ADSCs移植治疗DMD的安全性及可行性。方法 Mdx鼠60只,分为mdx对照组(30只)和mdx移植组(30只);正常C57小鼠为C57对照组(30只)。体外分离培养小鼠ADSCs,利用杆状病毒基因载体进行micro-dystrophin基因修饰;将基因修饰后的ADSCs经尾静脉移植到mdx鼠体内。于移植后检测mdx鼠的运动功能(采用主动牵引实验和被动转棒实验)、血清CK水平、肌肉病理改变以及肌肉micro-dystrophin表达水平。结果经micro-dystrophin基因修饰的ADSCs移植后,能够重建mdx鼠的micro-dystrophin表达,一定程度上减轻并逆转肌肉的病理损害,进而降低血清CK水平,mdx鼠整体运动功能也有一定改善。结论 ADSCs治疗mdx鼠后,可部分重建模型鼠的dystrophin表达,改善肌肉的病理损害,表明ADSCs是有希望治愈DMD的方法之一。Aim To explore the safety and feasibility of adipose-derived stem cells（ADSCs） transplantation on Duchenne muscular dystrophy（DMD） treatment, in which gene defect on mdx mouse was repaired with recombinant baculovirus carrying micro-dystrophin. Methods Adipose stem cells of mdx mouse were isolated and cultured in vitro. Gene defect was repaired with recombinant baculovirus. The modified stem cells were injected DMD mouse model through tail vein. Motor function, serum CK levels, muscle pathology and muscle dystrophin expression were observed after transplantation. Results After transplantation, micro-dystrophin expression in DMD mouse model could be rebuilt, pathological damage on muscles and serum CK levels were reduced, motor function of mouse model showed improvement. Conclusion After transplantation, gene expression can be partially reconstructed, pathological damage can be improved. These results suggested that stem cell transplantation should be a promising cure therapy for DMD.

关 键 词：脂肪干细胞 细胞移植 假肥大型肌营养不良症 

分 类 号：R746.2[医药卫生—神经病学与精神病学] Q189[医药卫生—临床医学]