Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells.
Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells.
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DOI：
10.1155/2013/198762
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发表时间：
2013-09-28
期刊：
影响因子：
--
通讯作者：
Tobita K
中科院分区：
文献类型：
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作者：
Tchao J;Kim JJ;Lin B;Salama G;Lo CW;Yang L;Tobita K
在发育过程中，心肌和骨骼肌共享主要的转录因子和肌节蛋白，这些转录因子和肌节蛋白通常被认为是心肌或骨骼肌特异性的，但在终末分化的成体心肌或骨骼肌中并非两者都有。在这里，我们调查是否从人骨骼肌来源的干细胞（MDSC）构建的人工肌肉重演心肌和骨骼肌之间的发育相似性。我们使用MDSC构建了三维胶原基工程化肌肉组织（EMT）（MDSC-EMT），并使用诱导多能干（iPS）细胞衍生的心肌细胞（iPS-EMT）比较了EMT的生化和收缩特性。MDSC-EMT和iPS-EMT均表达心肌特异性肌钙蛋白、快速骨骼肌肌球蛋白重链和连接蛋白-43，模拟发育中的心肌或骨骼肌。在转录水平，MDSC-EMT和iPS-EMT上调心肌和骨骼肌特异性基因，并表达Nkx2.5和Myo-D蛋白。MDSC-EMT显示细胞内钙离子瞬变和对异丙肾上腺素的反应。MDSC-EMT的收缩力测量证明了两种组织中未成熟心肌和骨骼肌的功能特性。结果表明，来自MDSC的EMT模拟发育中的心肌和骨骼肌，并且可以作为有用的体外功能横纹肌模型，用于研究MDSC用于心脏修复的干细胞分化和治疗选择。
During development, cardiac and skeletal muscle share major transcription factors and sarcomere proteins which were generally regarded as specific to either cardiac or skeletal muscle but not both in terminally differentiated adult cardiac or skeletal muscle. Here, we investigated whether artificial muscle constructed from human skeletal muscle derived stem cells (MDSCs) recapitulates developmental similarities between cardiac and skeletal muscle. We constructed 3-dimensional collagen-based engineered muscle tissue (EMT) using MDSCs (MDSC-EMT) and compared the biochemical and contractile properties with EMT using induced pluripotent stem (iPS) cell-derived cardiac cells (iPS-EMT). Both MDSC-EMT and iPS-EMT expressed cardiac specific troponins, fast skeletal muscle myosin heavy chain, and connexin-43 mimicking developing cardiac or skeletal muscle. At the transcriptional level, MDSC-EMT and iPS-EMT upregulated both cardiac and skeletal muscle-specific genes and expressed Nkx2.5 and Myo-D proteins. MDSC-EMT displayed intracellular calcium ion transients and responses to isoproterenol. Contractile force measurements of MDSC-EMT demonstrated functional properties of immature cardiac and skeletal muscle in both tissues. Results suggest that the EMT from MDSCs mimics developing cardiac and skeletal muscle and can serve as a useful in vitro functioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair.