Growth Factors for Skeletal Muscle Tissue Engineering.

Growth Factors for Skeletal Muscle Tissue Engineering.
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DOI:
10.1159/000444671
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发表时间:
2016
期刊:
Cells, tissues, organs
影响因子:
--
通讯作者:
Larkin LM
Larkin LM
中科院分区:
其他
文献类型:
--
作者:
Syverud BC;VanDusen KW;Larkin LM

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组织工程化骨骼肌有望成为修复肌肉体积损失的移植组织来源和药物试验的模型系统。为了达到这一潜力,工程组织必须提前过去的新生儿表型,其特征是目前的最先进的。在这篇综述中,我们描述了原生骨骼肌的发展,并确定重要的生长因子控制这一过程。通过比较体内肌生成体外卫星细胞培养和组织工程方法,几个关键的相似性和差异,可能会潜在地推进组织工程骨骼肌被确定。特别地,使用HGF和FGF来加速卫星细胞活化和增殖,随后添加IGF作为有效的分化诱导剂是经证实的用于增加工程化肌肉中的肌生成的方法。此外,我们回顾了我们最近的新应用地塞米松(DEX),糖皮质激素,刺激成肌细胞分化,在骨骼肌组织工程。使用我们建立的骨骼肌单位(SMU)制造协议,DEX的时间和剂量依赖性的影响进行了测量。与未处理的对照组相比,补充的SMU表现出先进的肌节结构和显著增加的肌管直径和肌管融合指数。最重要的是,这些SMU在力产生方面表现出5倍的增长。因此,我们得出结论,DEX可能有助于改善肌生成,推进肌肉结构,并增加工程骨骼肌的力量产生。
Tissue engineered skeletal muscle holds promise as a source of graft tissue for repair of volumetric muscle loss and as a model system for pharmaceutical testing. To reach this potential, engineered tissues must advance past the neonatal phenotype that characterizes the current state of the art. In this review, we describe native skeletal muscle development and identify important growth factors controlling this process. By comparing in vivo myogenesis to in vitro satellite cell cultures and tissue engineering approaches, several key similarities and differences that may potentially advance tissue engineered skeletal muscle were identified. In particular, the use of HGF and FGF to accelerate satellite cell activation and proliferation, followed by addition of IGF as a potent inducer of differentiation are proven methods for increased myogenesis in engineered muscle. Additionally, we review our recent novel application of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation, in skeletal muscle tissue engineering. Using our established skeletal muscle unit (SMU) fabrication protocol, timing and dose dependent effects of DEX were measured. The supplemented SMUs demonstrated advanced sarcomeric structure and significantly increased myotube diameter and myotube fusion index, compared to untreated controls. Most significantly, these SMUs exhibited a 5-fold rise in force production. Thus, we concluded that DEX may serve to improve myogenesis, advance muscle structure, and increase force production in engineered skeletal muscle.
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