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Effects of substrate stiffness on the tenoinduction of human mesenchymal stem cells

机译:基材刚度对人间充质干细胞的网状凝固的影响

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摘要

Extracellular matrix modulus plays an important role in regulating cell morphology, proliferation and differentiation during regular and diseased states. Although the effects of substrate topography and modulus on MSC differentiation are well known with respect to osteogenesis and adipogenesis, there has been relatively little investigation on the effects of this phenomenon on tenogenesis. Furthermore, relative roles of topographical factors (matrix alignment vs. matrix modulus) in inducing tenogenic differentiation is not well understood. In this study we investigated the effects of modulus and topographical alignment of type I collagen substrate on tendon differentiation. Type I collagen sheet substrates with random topographical alignment were fabricated with their moduli tuned in the range of 0.1, 1, 10 and 100 MPa by using electrocompaction and controlled crosslinking. In one of the groups, topographical alignment was introduced at 10 MPa stiffness, by controlled unidirectional stretching of the sheet. RT-PCR, immunohistochemistry and immunofluorescence results showed that mimicking the tendon topography, i.e. increasing the substrate modulus as well as alignment increased the tenogenic differentiation. Higher substrate modulus increased the expression of COLI, COLIII, COMP and TSP-4 about 2-3-fold and increased the production of COLI, COLIII and TSP-4 about 2-4-fold. Substrate alignment up regulated COLIII and COMP expression by 2-fold. Therefore, the tenoinductive collagen material model developed in this study can be used in the research and development of tissue engineering tendon repair constructs in future.
机译:细胞外基质模量在规范细胞形态,常规和患病状态期间的分化中起着重要作用。尽管基材地形和模量对MSC分化的影响是众所周知的,但是对骨质发生和脂肪发生是众所周知的,但对这种现象对胎生物的影响进行了相对较少的调查。此外,诱导初始分化在诱导遗传分化中的地形因素(基质对准与基质模量)的相对作用。在该研究中,我们研究了I型胶原蛋白基质对肌腱分化的模量和地形比对的影响。通过使用电容和受控的交联在0.1,1,10和100MPa的范围内,用它们的模量制造具有随机地形比对的Ⅰ型胶原片基板。在其中一个组中,通过控制片材的单向拉伸,以10MPa刚度引入地形比对。 RT-PCR,免疫组织化学和免疫荧光结果表明,模拟肌腱形貌,即增加基底模量以及对准增加了遗传分化。较高的基底模量增加了大肠杆菌,COLIII,COM​​I,COM​​P和TSP-4的表达约2-3倍并增加了大肠杆菌,COLIII和TSP-4的产生约2-4倍。基板对准调节的Coliii和Comp表达2倍。因此,该研究中开发的该子诱导胶原材料模型可用于未来组织工程腱修复结构的研究和开发。

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  • 来源
    《Acta biomaterialia》 |2017年第2017期|共10页
  • 作者单位

    Case Western Reserve Univ Dept Mech &

    Aerosp Engn Cleveland OH 44106 USA;

    Case Western Reserve Univ Dept Mech &

    Aerosp Engn Cleveland OH 44106 USA;

    Case Western Reserve Univ Dept Mech &

    Aerosp Engn Cleveland OH 44106 USA;

    Case Western Reserve Univ Dept Mech &

    Aerosp Engn Cleveland OH 44106 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

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