Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues.

IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES npj Microgravity 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
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Abstract

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.

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模拟微重力削弱了三维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,但微重力对肌肉生成的影响及其机制仍不清楚。在这项研究中,我们利用胶原蛋白/Matrigel复合水凝胶和小鼠骨骼肌母细胞建立了一个工程肌肉组织(EMT)微观生理系统。这种三维 EMT 模型可对收缩功能进行无创定量评估。在应用 7 天的分化方案诱导肌管形成后,EMTs 明显表现出肉瘤生成、肌丝形成以及在电刺激下的同步抽搐和四肢收缩。利用这种三维 EMT 系统,我们使用随机定位机研究了 10-3 G 的模拟微重力对肌生成和收缩功能的影响。在模拟微重力条件下培养 5 天的 EMT 表现出明显的收缩力、肌纤维大小以及肌肉收缩蛋白、肌生成调节蛋白和线粒体生物生成相关蛋白的差异表达。这些结果表明,模拟微重力会减弱肌生成,导致肌肉功能受损。
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来源期刊
npj Microgravity
npj Microgravity Physics and Astronomy-Physics and Astronomy (miscellaneous)
CiteScore
7.30
自引率
7.80%
发文量
50
审稿时长
9 weeks
期刊介绍: A new open access, online-only, multidisciplinary research journal, npj Microgravity is dedicated to publishing the most important scientific advances in the life sciences, physical sciences, and engineering fields that are facilitated by spaceflight and analogue platforms.
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