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Functional regeneration of tissue engineered skeletal muscle in vitro is dependent on the inclusion of basement membrane proteins

机译:体外组织工程骨骼肌的功能再生取决于底座膜蛋白的包含

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Skeletal muscle has a high regenerative capacity, injuries trigger a regenerative program which restores tissue function to a level indistinguishable to the pre-injury state. However, in some cases where significant trauma occurs, such as injuries seen in military populations, the regenerative process is overwhelmed and cannot restore full function. Limited clinical interventions exist which can be used to promote regeneration and prevent the formation of non-regenerative defects following severe skeletal muscle trauma. Robust and reproducible techniques for modelling complex tissue responses are essential to promote the discovery of effective clinical interventions. Tissue engineering has been highlighted as an alternative method, allowing the generation of three-dimensional in vivo like tissues without laboratory animals. Reducing the requirement for animal models promotes rapid screening of potential clinical interventions, as these models are more easily manipulated, genetically and pharmacologically, and reduce the associated cost and complexity, whilst increasing access to models for laboratories without animal facilities. In this study, an in vitro chemical injury using barium chloride is validated using the C2C12 myoblast cell line, and is shown to selectively remove multinucleated myotubes, whilst retaining a regenerative mononuclear cell population. Monolayer cultures showed limited regenerative capacity, with basement membrane supplementation or extended regenerative time incapable of improving the regenerative response. Conversely tissue engineered skeletal muscles, supplemented with basement membrane proteins, showed full functional regeneration, and a broader in vivo like inflammatory response. This work outlines a freely available and open access methodology to produce a cell line-based tissue engineered model of skeletal muscle regeneration.
机译:骨骼肌具有很高的再生能力,伤害触发再生计划,将组织功能恢复到难以受伤状态的水平。然而,在某些情况下,在发生重大创伤的情况下,例如军用群体中看到的伤害,再生过程不堪重负,无法恢复全功能。存在有限的临床干预,可用于促进再生并防止在严重骨骼肌创伤后形成非再生缺陷。用于建模复杂组织反应的鲁棒和可重复的技术对于促进有效临床干预措施的发现是必不可少的。组织工程被突出显示为替代方法,允许在没有实验室动物的组织中产生三维。减少动物模型的要求促进了潜在的临床干预措施的快速筛选,因为这些模型更容易操纵,转基因和药理学,并降低相关成本和复杂性,同时增加对没有动物设施的实验室模型的机会。在该研究中,使用C2C12肌细胞线验证使用氯化钡的体外化学损伤,并且显示出选择性地除去多核肌管,同时保留再生单核细胞群。单层培养物显示出限量的再生能力,源自膜补充剂或延长的再生时间不能改善再生反应。相反,组织工程骨骼肌,补充有基底膜蛋白,表现出全功能再生,以及炎症反应等体内更宽。这项工作概述了自由和开放的接入方法,以产生基于细胞系的骨骼肌再生组织工程模型。

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