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首页> 外文期刊>International Journal of Tissue Engineering >Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells
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Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells

机译：从骨骼肌衍生的干细胞和诱导多能干细胞衍生的心肌细胞工程化的人类肌肉组织

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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 usefulin vitrofunctioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair.
机译：在发育过程中，心肌和骨骼肌共享主要的转录因子和肌小节蛋白，它们通常被认为对心肌或骨骼肌具有特异性，但在终末分化的成年心肌或骨骼肌中均不具有。在这里，我们调查了由人类骨骼肌衍生干细胞（MDSCs）构成的人造肌肉是否能概括心肌和骨骼肌之间的发育相似性。我们使用MDSC（MDSC-EMT）构建了基于3维胶原蛋白的工程肌组织（EMT），并使用诱导多能干（iPS）细胞衍生的心肌细胞（iPS-EMT）将其生化和收缩特性与EMT进行了比较。 MDSC-EMT和iPS-EMT均表达心脏特异性肌钙蛋白，快速骨骼肌肌球蛋白重链和模拟发育中的心肌或骨骼肌的连接蛋白43。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的收缩力测量结果显示了两种组织中未成熟的心肌和骨骼肌的功能特性。结果表明，来自MDSC的EMT模仿了心脏和骨骼肌的发育，并且可以作为有用的体外横纹肌模型用于研究干细胞分化和MDSC用于心脏修复的治疗选择。

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