Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats.
Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats.
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植入过度表达肌细胞生成素的肌肉卫星细胞可改善大鼠失神经肌肉萎缩
DOI：
10.1590/1414-431x20155124
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Duan T
中科院分区：
文献类型：
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作者：
Shen H;Lv Y;Shen XQ;Xu JH;Lu H;Fu LC;Duan T
本研究评价了肌肉卫星细胞(MSCs)过表达肌生成素(MyoG)对失神经肌肉萎缩的影响。分离大鼠骨髓间充质干细胞，用MyoG-EGFP载体GV143转染人MSCs。术后1周将转MyoG基因的骨髓间充质干细胞(MTM)移植到大鼠腓肠肌内。对照组包括注射未转基因的MSCs或仅注射赋形剂。分别于移植后2、4、24周取材进行肌肉分析。免疫荧光证实MyoG在MTM中高表达。注射MTM后2周肌肉湿重比(67.17±6.79)显著低于注射MSCs组(58.83±5.31)和载药组(53.00±7.67)(t=2.37，P=0.04和t=3.39，P=0.007)。肌纤维横截面积在注射后2周(2.63×103±0.39×103)也大于注射骨髓基质细胞(1.99×103±0.58×103)或单独注射载体(1.57×103±0.47×103；t=2.24，P=0.049和t=4.22，P=0.002)。在注射后4周和24周，三个实验组的肌肉质量和纤维横截面积相似。免疫组织化学显示MTM组有较大的MyoG阳性纤维。注射后2周，MTM组的MyoG mRNA表达(3.18±1.13)也高于其他组(1.41±0.65和1.03±0.19)(t=2.72，P=0.04)。移植的MTM延缓了失神经肌肉的短期萎缩。这种方法可以被优化为一种新的独立治疗方法，或作为外科手术重新支配受损肌肉的桥梁。
This study evaluated the effect of muscle satellite cells (MSCs) overexpressing myogenin (MyoG) on denervated muscle atrophy. Rat MSCs were isolated and transfected with the MyoG-EGFP plasmid vector GV143. MyoG-transfected MSCs (MTMs) were transplanted into rat gastrocnemius muscles at 1 week after surgical denervation. Controls included injections of untransfected MSCs or the vehicle only. Muscles were harvested and analyzed at 2, 4, and 24 weeks post-transplantation. Immunofluorescence confirmed MyoG overexpression in MTMs. The muscle wet weight ratio was significantly reduced at 2 weeks after MTM injection (67.17±6.79) compared with muscles injected with MSCs (58.83±5.31) or the vehicle (53.00±7.67; t=2.37, P=0.04 and t=3.39, P=0.007, respectively). The muscle fiber cross-sectional area was also larger at 2 weeks after MTM injection (2.63×103±0.39×103) compared with MSC injection (1.99×103±0.58×103) or the vehicle only (1.57×103±0.47×103; t=2.24, P=0.049 and t=4.22, P=0.002, respectively). At 4 and 24 weeks post-injection, the muscle mass and fiber cross-sectional area were similar across all three experimental groups. Immunohistochemistry showed that the MTM group had larger MyoG-positive fibers. The MTM group (3.18±1.13) also had higher expression of MyoG mRNA than other groups (1.41±0.65 and 1.03±0.19) at 2 weeks after injection (t=2.72, P=0.04). Transplanted MTMs delayed short-term atrophy of denervated muscles. This approach can be optimized as a novel stand-alone therapy or as a bridge to surgical re-innervation of damaged muscles.