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Micro-dsytrophin基因修饰的骨髓间充质干细胞移植后mdx鼠腓肠肌病理改变及micro-dystrophin的表达 被引量:4

Pathological Change and Micro-dsytrophin Expression in mdx Mice after Transplantation of Bone Marrow Mesenchymal Stem Cells Modified by Micro-dystrophin Gene
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摘要 目的探讨自体骨髓间充质干细胞(mMSCs)携带micro-dystrophin基因在移植鼠体内分化为有功能肌细胞的可能性。方法采用脂质体介导micro-dystrophin基因转染mdx小鼠mMSCs,通过尾静脉注射移植治疗mdx鼠,在移植后不同时间点对腓肠肌进行HE染色、计数核中心移位纤维(CNF)比例,并用免疫荧光法检测micro-dystrophin的表达。结果移植后各时间点腓肠肌病理改变较对照组有所改善,CNF比例下降,差异有统计学意义,部分肌细胞膜能表达micro-dystrophin蛋白,并随移植时间延长micro-dystrophin阳性肌纤维比例增加,分别达到3%(8周时)、6%(12周时)和8%(16周时)。结论自体mMSCs可携带外源性micro-dys-trophin基因在受体鼠体内分化为micro-dystrophin阳性肌细胞。 Objective To study the possibility of genetically modified autologous mesenchymal stem cells differentiated into functional muscle eells in transplanted mdx mice. Methods The plasrnid pcDNA3. 1 (+)/ micro-dystrophin was transfeeted into mMSCs by lipofectamine. Then the microdys-mMSCs were transplanted into mdx through the tail vein. The gastrocnemius muscles from mice at each time point were sectioned at -20 ℃ in 6 μm sections. After HE staining, morphology of myocytes was observed and the rate of centrally nucleated fibers ( CNF ) was calculated. Expression of micro dystrophin was detected using the method of immunofluorescence. Results After transplantation of microdys-mMSCs, the pathological change in muscles was improved and the proportion of CNF was decreased. Compared with non-transplanted mice, the CNF rate in the gastrocnemius of mice was reduced statistically. Over time, the dystrophin positive fibres increased 3% (at 8 weeks), 6 % (at 12 weeks), 8 % ( at 16 weeks) in the gastrocnemius respectively. Conclusions The geneticallymodified autologous MSCs by micro-dsytrophin gene could differentiated into micro-dystrophin positive cells in transplanted mdx mice.
出处 《中国神经免疫学和神经病学杂志》 CAS 2008年第6期404-407,473,共5页 Chinese Journal of Neuroimmunology and Neurology
基金 国家自然科学基金资助项目(30370510) 广东省自然科学基金资助项目(31693)
关键词 DUCHENNE型肌营养不良症 MDX 骨髓间充质干细胞 微小dystrophin基因 Duchenne muscular dystrophy mdx bone marrow mesenchymal stem cell micro-dystrophin
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