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Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues
npj Microgravity ( IF 5.1 ) Pub Date : 2024-02-16 , DOI: 10.1038/s41526-024-00353-z
Zhanping Ren , Eun Hyun Ahn , Minjae Do , Devin B. Mair , Amir Monemianesfahani , Peter H. U. Lee , Deok-Ho Kim

While the effects of microgravity on inducing skeletal muscle atrophy have been extensively studied, the impacts of microgravity on myogenesis and its mechanisms remain unclear. In this study, we developed a microphysiological system of engineered muscle tissue (EMT) fabricated using a collagen / Matrigel composite hydrogel and murine skeletal myoblasts. This 3D EMT model allows non-invasive quantitative assessment of contractile function. After applying a 7-day differentiation protocol to induce myotube formation, the EMTs clearly exhibited sarcomerogenesis, myofilament formation, and synchronous twitch and tetanic contractions with electrical stimuli. Using this 3D EMT system, we investigated the effects of simulated microgravity at 10−3 G on myogenesis and contractile function utilizing a random positioning machine. EMTs cultured for 5 days in simulated microgravity exhibited significantly reduced contractile forces, myofiber size, and differential expression of muscle contractile, myogenesis regulatory, and mitochondrial biogenesis-related proteins. These results indicate simulated microgravity attenuates myogenesis, resulting in impaired muscle function.



中文翻译:

模拟微重力减弱 3D 工程骨骼肌组织的肌生成和收缩功能

虽然微重力对诱导骨骼肌萎缩的影响已被广泛研究,但微重力对肌生成的影响及其机制仍不清楚。在这项研究中,我们开发了一种使用胶原蛋白/基质胶复合水凝胶和小鼠骨骼成肌细胞制造的工程肌肉组织(EMT)的微生理系统。该 3D EMT 模型可以对收缩功能进行非侵入性定量评估。在应用 7 天分化方案诱导肌管形成后,EMT 清楚地表现出肌瘤生成、肌丝形成以及电刺激下的同步抽搐和强直收缩。使用该 3D EMT 系统,我们利用随机定位机研究了 10 -3  G模拟微重力对肌生成和收缩功能的影响。在模拟微重力中培养 5 天的 EMT 表现出显着降低的收缩力、肌纤维尺寸以及肌肉收缩、肌生成调节和线粒体生物发生相关蛋白的差异表达。这些结果表明模拟微重力会减弱肌肉生成,导致肌肉功能受损。

更新日期:2024-02-17
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