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Regulation of Myogenic Activity by Substrate and Electrical Stimulation In Vitro

机译:通过基质和体外电刺激调节肌原性活性

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Skeletal muscle has a remarkable regenerative capacity in response to mild injury. However, when muscle is severely injured, muscle regeneration is impaired due to the loss of muscle-resident stem cells, known as satellite cells. Fibrotic tissue, primarily comprising collagen I (COL), is deposited with this critical loss of muscle. In recent studies, supplementation of laminin (LM)-111 has been shown to improve skeletal muscle regeneration in several models of disease and injury. Additionally, electrical stimulation (E-stim) has been investigated as a possible rehabilitation therapy to improve muscle's functional recovery. This study investigated the role of E-stim and substrate in regulating myogenic response. C2C12 myoblasts were allowed to differentiate into myotubes on COL- and LM-coated polydimethylsiloxane molds. The myotubes were subjected to E-stim and compared with nonstimulated controls. While E-stim resulted in increased myogenic activity, irrespective of substrate, LM supported increased proliferation and uniform distribution of C2C12 myoblasts. In addition, C2C12 myoblasts cultured on LM showed higher Sirtuin 1, mammalian target of rapamycin, desmin, nitric oxide, and vascular endothelial growth factor expression. Taken together, these results suggest that an LM substrate is more conducive to myoblast growth and differentiation in response to E-stim in vitro .
机译:骨骼肌对轻度损伤具有显着的再生能力。但是,当肌肉受到严重伤害时,由于肌肉驻留干细胞(称为卫星细胞)的丢失,肌肉的再生会受到损害。主要包括胶原蛋白I(COL)的纤维化组织沉积有这种严重的肌肉丢失。在最近的研究中,已证明补充层粘连蛋白(LM)-111可以改善几种疾病和损伤模型中的骨骼肌再生。另外,已经研究了电刺激(E-stim)作为改善肌肉功能恢复的可能的康复疗法。这项研究调查了E刺激物和底物在调节成肌反应中的作用。在COL和LM涂层的聚二甲基硅氧烷模具上,将C2C12成肌细胞分化为肌管。使肌管受到E刺激,并与未刺激的对照组进行比较。尽管E-stim导致成肌活性增加,但无论底物如何,LM都支持C2C12成肌细胞的增生和均匀分布。此外,在LM上培养的C2C12成肌细胞显示出较高的Sirtuin 1,是哺乳动物雷帕霉素,结蛋白,一氧化氮和血管内皮生长因子表达的靶标。综上所述,这些结果表明,LM底物在体外对E-刺激的应答中更有利于成肌细胞的生长和分化。

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