In vitro drug testing based on contractile activity of C2C12 cells in an epigenetic drug model.
In vitro drug testing based on contractile activity of C2C12 cells in an epigenetic drug model.
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DOI：
10.1038/srep44570
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发表时间：
2017-03-16
影响因子：
4.6
通讯作者：
Kamihira M
中科院分区：
文献类型：
--
作者：
Ikeda K;Ito A;Imada R;Sato M;Kawabe Y;Kamihira M
骨骼肌组织工程在药理学研究中具有很大的前景。在此，我们展示了一个使用组织工程骨骼肌结构的体外药物测试系统。在表观遗传药物的作用下，二维细胞培养可促进C2C12成肌细胞的肌管分化，但三维细胞培养制备的组织工程骨骼肌构建体的收缩力产生水平与二维细胞培养的肌管分化水平不相关。相反，二维细胞培养中的肌节形成和收缩活性与组织工程骨骼肌结构的收缩力产生高度相关。在所测试的表观遗传药物中，曲古霉素A显著改善了组织工程骨骼肌结构的收缩力产生。在曲古霉素A的作用下，卵泡抑素的表达也增强，提示卵泡抑素在肌肉组织肌瘤形成中的重要性。这些观察结果表明，收缩性数据是必不可少的体外药物筛选。
Skeletal muscle tissue engineering holds great promise for pharmacological studies. Herein, we demonstrated an in vitro drug testing system using tissue-engineered skeletal muscle constructs. In response to epigenetic drugs, myotube differentiation of C2C12 myoblast cells was promoted in two-dimensional cell cultures, but the levels of contractile force generation of tissue-engineered skeletal muscle constructs prepared by three-dimensional cell cultures were not correlated with the levels of myotube differentiation in two-dimensional cell cultures. In contrast, sarcomere formation and contractile activity in two-dimensional cell cultures were highly correlated with contractile force generation of tissue-engineered skeletal muscle constructs. Among the epigenetic drugs tested, trichostatin A significantly improved contractile force generation of tissue-engineered skeletal muscle constructs. Follistatin expression was also enhanced by trichostatin A treatment, suggesting the importance of follistatin in sarcomere formation of muscular tissues. These observations indicate that contractility data are indispensable for in vitro drug screening.