A central challenge in tissue engineering is obtaining a suitable cell type with a capable delivery vehicle to replace or repair damaged or diseased tissues with tissue mimics. Notably, for skeletal muscle tissue engineering, given the inadequate availability and regenerative capability of endogenous myogenic progenitor cells as well as the tumorigenic risks presented by the currently available pluri- and multipotent stem cells, seeking a safe regenerative cell source is urgently demanded. To conquer this problem, we previously established a novel reprogramming technology that can generate multipotent cells from dermal fibroblasts using a single protein, fibromodulin (FMOD). The yield FMOD-reprogrammed (FReP) cells exhibit exceeding myogenic capability without tumorigenic risk, making them a promising and safe cell source for skeletal muscle establishment. In addition to using the optimal cell for implantation, it is equally essential to maintain cellular localization and retention in the recipient tissue environment for critical-sized muscle tissue establishment. In this study, we demonstrate that the photopolymerizable methacrylated glycol chitosan (MeGC)/type I collagen (ColI)-hydrogel provides a desirable microenvironment for encapsulated FReP cell survival, spreading, extension, and formation of myotubes in the hydrogel three-dimensionally in vitro, without undesired osteogenic, chondrogenic, or tenogenic differentiation. Furthermore, gene profiling revealed a paired box 7 (PAX7) → myogenic factor 5 (MYF5) → myogenic determination 1 (MYOD1) → myogenin (MYOG) → myosin cassette elevation in the encapsulated FReP cells during myogenic differentiation, which is similar to that of the predominant driver of endogenous skeletal muscle regeneration, satellite cells. These findings constitute the evidence that the FReP cell-MeGC/ColI-hydrogel construct is a promising tissue engineering mimic for skeletal muscle generation in vitro, and thus possesses the extraordinary potential for further in vivo validation.

中文翻译：

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用于肌肉再生的可光聚合水凝胶封装的纤维调节蛋白重编程细胞。

组织工程中的一个核心挑战是获得合适的细胞类型，以及一种能够用组织模拟物替换或修复受损或患病组织的运载工具。值得注意的是，对于骨骼肌组织工程，鉴于内源性生肌祖细胞的可用性和再生能力不足，以及目前可用的多能和多能干细胞存在致瘤风险，迫切需要寻求安全的再生细胞来源。为了克服这个问题，我们之前建立了一种新的重编程技术，该技术可以使用单一蛋白质纤维调节蛋白 (FMOD) 从真皮成纤维细胞生成多能细胞。FMOD 重编程 (FReP) 细胞的产量表现出超强的生肌能力，没有致瘤风险，使它们成为骨骼肌建立的有前途且安全的细胞来源。除了使用最佳细胞进行植入外，维持细胞定位和保留在受体组织环境中以建立临界尺寸的肌肉组织也同样重要。在这项研究中，我们证明了可光聚合的甲基丙烯酸乙二醇壳聚糖 (MeGC)/I 型胶原 (ColI)-水凝胶为封装的 FReP 细胞存活、扩散、延伸和在水凝胶中三维形成肌管提供了理想的微环境在体外，没有不希望的成骨、成软骨或成腱分化。此外，基因分析揭示了成对的框 7 (PAX7) →肌源因子 5 (MYF5) →肌源性测定 1 (MYOD1) →肌细胞生成素 (MYOG) →肌原性分化过程中封装的 FReP 细胞中的肌球蛋白盒升高，这类似于内源性骨骼肌再生的主要驱动力，卫星细胞。这些发现证明了 FReP 细胞-MeGC/ColI-水凝胶构建体是一种有前景的体外骨骼肌生成组织工程模拟物，因此具有进一步在体内产生的非凡潜力。 验证。