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骨髓干细胞移植改善抗肌萎缩蛋白/肌营养不良蛋白相关蛋白基因双敲除小鼠的运动功能

[Bone marrow stem cells transplantation improve locomotive function of dystrophin/utrophin gene double knock-out mice].

作者信息

Zhang Cheng, Chen Song-lin, Liu Xiao-rong, Huang Wen, Zhang Wei-xi, Lu Xi-lin

机构信息

Department of Neurology, First Affiliated Hospital of Sun Yat-sen, Guangzhou, 510080, China.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Apr;25(2):160-3.

Abstract

OBJECTIVE

Study the improvement of locomotive faculty of dystrophin/utropin gene double knock-out mice (dko mice) by transplanting bone marrow stem cells.

METHODS

The bone marrow stem cells of C57BL/6 mice (4- to 5-weeks age) were cultured in vitro for three days, before transplanted intravenously (1.0 x 10(7) for each) into 11 dko mice (7- to 8-weeks age). The dko mice were irridiated with 7Gy gamma-ray before transplantation. 8-9 weeks after transplantation, the locomotroy function, electromyography items and expression of dystrophin in transplanted mice and controls were observed.

RESULTS

8-9 weeks after transplantation, the dropping times of hauling wire were 3.09 +/- 2.47, compared with that of the control dko mice(16.78 +/- 3.60), there are distinct differences. About electromyography items, the duration of active potential and amplitude of maxim contractions were (4.99 +/- 1.62) ms and(2872 +/- 1474.33) microV, compare with those of control dko mice(3.69 +/- 0.40) ms and(1210.0 +/- 551.0) microV, respectively, about 7% fibers of the muscle tissue of transplanted dko mice expressed dystrophin protein.

CONCLUSIONS

8-9 weeks after transplanted with homology bone marrow stem cells, the locomotive function and electromyography items of transplanted dko mice were obviously improved, and about 7% muscle tissue fibers of the mice expressing dystrophin protein were observed. It suggested that there is an ideal prospect for DMD therapy with bone marrow stem cells transplantation.

摘要

目的

研究通过移植骨髓干细胞改善抗肌萎缩蛋白/泛肌营养不良蛋白基因双敲除小鼠(dko小鼠)的运动能力。

方法

将4至5周龄C57BL/6小鼠的骨髓干细胞体外培养3天,然后静脉注射(每只1.0×10⁷个)到11只7至8周龄的dko小鼠体内。移植前对dko小鼠进行7Gy的γ射线照射。移植后8至9周,观察移植小鼠和对照小鼠的运动功能、肌电图指标以及抗肌萎缩蛋白的表达。

结果

移植后8至9周,牵引线掉落时间为3.09±2.47,与对照dko小鼠(16.78±3.60)相比,有明显差异。关于肌电图指标,动作电位持续时间和最大收缩幅度分别为(4.99±1.62)ms和(2872±1474.33)μV,与对照dko小鼠(3.69±0.40)ms和(1210.0±551.0)μV相比,移植的dko小鼠肌肉组织中约7%的纤维表达抗肌萎缩蛋白。

结论

同源骨髓干细胞移植8至9周后,移植的dko小鼠的运动功能和肌电图指标明显改善,且观察到小鼠约7%的肌肉组织纤维表达抗肌萎缩蛋白。这表明骨髓干细胞移植治疗杜氏肌营养不良症有理想的前景。

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