In vivo tendon engineering with skeletal muscle derived cells in a mouse model

In vivo tendon engineering with skeletal muscle derived cells in a mouse model
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在小鼠模型中使用骨骼肌衍生细胞进行体内肌腱工程

DOI:
10.1016/j.biomaterials.2012.05.022
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发表时间:
2012-09-01
期刊:
影响因子:
14
通讯作者:
Liu, Wei
Liu, Wei
中科院分区:
工程技术1区
文献类型:
--
作者:
Chen, Bo;Wang, Bin;Liu, Wei

文献摘要

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设计一种具有良好力学性能的功能性肌腱是其最终应用的目标。骨骼肌和肌腱在发育过程中有着密切的联系,它们都能动态地承受强大的机械载荷。本研究探讨了用小鼠骨骼肌源性细胞(MDCs)和小鼠肌腱细胞作为对照来构建更强肌腱的可能性。结果表明,MDCs和腱细胞均表达生长分化因子8(GDF-8)、I、III、VI型胶原、巩膜轴蛋白和腱调节蛋白,而MyoD基因仅在MDCs中表达。定量分析显示,MDCs表达更高水平的GDF-8、胶原III和VI(p < 0.05),而腱细胞表达更高水平的胶原I、巩膜轴和腱调节蛋白(p < 0.05)。有趣的是,MDCs增殖更快,S + G2/M期的细胞比腱细胞多(p < 0.05)。与腱细胞工程化肌腱相比,MDCs与PGA纤维复合后,形成的工程化肌腱质量更好,胶原结构更成熟,胶原纤维更粗。生物化学上,前者比后者产生更多的VI型胶原和核心蛋白聚糖。在功能上,MDC工程化肌腱表现出比肌腱细胞工程化肌腱更强的力学性能,包括最大载荷、刚度、拉伸强度和杨氏模量(p < 0.05)。而且随着注入时间的增加。MDCs逐渐失去MyoD和结蛋白的肌源性分子的表达,并获得肌腱调节蛋白(肌腱细胞的标志物)的表达。总的来说,这些结果表明,MDCs可以作为一个理想的替代细胞来源工程功能肌腱组织。(C)2012爱思唯尔有限公司保留所有权利。
Engineering a functional tendon with strong mechanical property remains an aim to be achieved for its eventual application. Both skeletal muscle and tendon are closely associated during their development and both can bear strong mechanical loading dynamically. This study explored the possibility of engineering stronger tendons with mouse skeletal muscle derived cells (MDCs) and with mouse tenocytes as a control. The results demonstrated that both MDCs and tenocytes shared the gene expression of growth differentiation factor-8 (GDF-8), collagens I, III, VI, scleraxis and tenomodulin, but with MyoD gene expression only in MDCs. Quantitatively, MDCs expressed higher levels of GDF-8, collagens III and VI (p < 0.05), whereas tenocytes expressed higher levels of collagen I, scleraxis and tenomodulin (p < 0.05). Interestingly, MDCs proliferated faster with more cells in S + G2/M phases than tenocytes (p < 0.05). After been seeded on polyglycolic acid (PGA) fibers, MDCs formed better quality engineered tendons with more mature collagen structure and thicker collagen fibrils as opposed to tenocyte engineered tendons. Biochemically, more collagen VI and decorin were produced in the former than in the later. Functionally, MDC engineered tendons exhibited stronger mechanical properties than tenocyte engineered tendons, including maximal load, stiffness, tensile strength and Young's modulus (p < 0.05). Furthermore, with the increase of implantation time. MDCs gradually lost their expression of myogenic molecules of MyoD and desmin and gained the expression of tenomodulin, a marker for tenocytes. Collectively, these results indicate that MDCs may serve as a desirable alternative cell source for engineering functional tendon tissue. (C) 2012 Elsevier Ltd. All rights reserved.