Three-dimensional contractile muscle tissue consisting of human skeletal myocyte cell line
Three-dimensional contractile muscle tissue consisting of human skeletal myocyte cell line
复制标题
由人骨骼肌细胞系组成的三维收缩肌组织
DOI：
10.1016/j.yexcr.2018.06.015
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发表时间：
2018
影响因子：
3.7
通讯作者：
Takeuchi Shoji
中科院分区：
文献类型：
--
作者：
Shima Ai;Morimoto Yuya;Sweeney H. Lee;Takeuchi Shoji
本文描述了一种从细胞系构建三维 (3D) 收缩性人体骨骼肌组织的方法。 3D 组织被制造为基于纤维的结构，并通过锚定其两端在张力下培养两周。虽然本研究中使用的永生化人类骨骼肌细胞的肌管在传统的二维 (2D) 单层培养中从未收缩，但 3D 组织中的肌管表现出高频自发收缩，并对电刺激做出反应。免疫荧光显示3D组织中的肌管有肌节并表达兰尼碱受体（RyR）和肌/内质网Ca2+-ATP酶（SERCA）。此外，还观察到 3D 组织中肌管的细胞内钙振荡。这些结果表明，与 2D 培养相比，3D 培养使肌细胞系达到更高的成熟状态。由于收缩是骨骼肌最重要的特征，我们相信具有收缩能力的 3D 人体肌肉组织将成为基础生物学研究和药物发现的有用工具，作为肌肉芯片之一。
This paper describes a method to construct three-dimensional (3D) contractile human skeletal muscle tissues from a cell line. The 3D tissue was fabricated as a fiber-based structure and cultured for two weeks under tension by anchoring its both ends. While myotubes from the immortalized human skeletal myocytes used in this study never contracted in the conventional two-dimensional (2D) monolayer culture, myotubes in the 3D tissue showed spontaneous contraction at a high frequency and also reacted to the electrical stimulation. Immunofluorescence revealed that the myotubes in the 3D tissues had sarcomeres and expressed ryanodine receptor (RyR) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). In addition, intracellular calcium oscillations in the myotubes in the 3D tissue were observed. These results indicated that the 3D culture enabled the myocyte cell line to reach a more highly matured state compared to 2D culture. Since contraction is the most significant feature of skeletal muscle, we believe that our 3D human muscle tissue with the contractile ability would be a useful tool for both basic biology research and drug discovery as one of the muscle-on-chips.