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首页> 外文学位 >Tendon extracellular matrix: Tenogenic activity on mesenchymal stem cells and utility in tendon tissue engineering.
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Tendon extracellular matrix: Tenogenic activity on mesenchymal stem cells and utility in tendon tissue engineering.

机译：肌腱细胞外基质：对间充质干细胞的肌腱活性及其在肌腱组织工程中的用途。

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摘要

Because of the limited and unsatisfactory outcomes of clinical tendon repair, tissue engineering approaches using adult mesenchymal stem cells (MSCs) are being considered a promising alternative healing strategy for injured tendon tissues. Successful and functional tendon tissue engineering depends on harnessing the biochemical cues presented by the native tendon extracellular matrix (ECM) and the embedded tissue-specific bio-factors. We have prepared and characterized the biological activities of a soluble extract of decellularized tendon ECM (tECM) on adult adipose derived stem cells (ASCs) on the basis of histological, biochemical, and gene expression analyses. Our results revealed the tenogenic effect of tECM on hASCs cultured in a 3-dimensional (3D) collagen scaffold under uniaxial tension. The presence of tECM also suppressed the osteogenic differentiation of hASCs induced by uniaxial tension and enhanced scaffold mechanical strength, accompanied by reduced expression and activity of matrix metalloproteinases (MMPs). Furthermore, we found that tECM enhanced the proliferation and TGF-beta3 induced tenogenesis of ASCs, and modulated matrix deposition and organization by ASCs seeded in 3D fibrous scaffolds. These findings support the utility of tECM in creating biofunctional scaffolds for tendon tissue engineering. We also report here the development of a novel composite fibrous scaffold as a tendon graft fabricated by co-electrospinning of poly-epsilon-caprolactone (PCL) and methacrylated gelatin (mGLT), which allowed the encapsulation of ASCs within the scaffold upon visible light induced gelatin photo-crosslinking, as well as the formation of stable, crosslinked multi-layered constructs. This scaffold design may improve cellbased tendon regeneration by serving as an effective reservoir of tECM and tenogenic growth factors to recapitulate the structural and biochemical characteristics of native tendon tissue. Our findings should lead to translational tissue engineering applications that will improve patient outcomes in the context of clinical tendon repair.
机译：由于临床腱修复的局限性和不令人满意的结果，使用成年间充质干细胞（MSC）的组织工程方法被认为是一种理想的替代方法，可用于治疗受伤的腱组织。成功且功能正常的肌腱组织工程取决于利用天然肌腱细胞外基质（ECM）和嵌入的组织特异性生物因子所提供的生化线索。我们根据组织学，生化和基因表达分析，制备并表征了脱细胞肌腱ECM（tECM）可溶性提取物对成年脂肪衍生干细胞（ASC）的生物学活性。我们的研究结果揭示了tECM对在3维（3D）胶原蛋白支架中在单轴张力下培养的hASC的成腱作用。 tECM的存在还抑制了由单轴张力和增强的支架机械强度诱导的hASC的成骨分化，同时降低了基质金属蛋白酶（MMP）的表达和活性。此外，我们发现tECM增强了ASC的增殖和TGF-β3诱导的肌腱发生，并通过植入3D纤维支架中的ASC调节了基质的沉积和组织。这些发现支持tECM在创建用于肌腱组织工程的生物功能支架中的实用性。我们还在这里报告了一种新型复合纤维支架的开发，该复合纤维支架是通过聚电-己内酯（PCL）和甲基丙烯酸明胶（mGLT）的共电纺丝制成的肌腱移植物，允许在可见光诱导下将ASC封装在支架中明胶光交联以及稳定，交联的多层构建体的形成。这种支架设计可通过充当tECM和腱生生长因子的有效库来概括天然肌腱组织的结构和生化特征来改善基于细胞的肌腱再生。我们的发现将导致平移组织工程的应用，从而在临床肌腱修复的背景下改善患者的预后。

著录项

  • 作者

    Yang, Guang.;

  • 作者单位

    University of Pittsburgh.;

  • 授予单位 University of Pittsburgh.;
  • 学科 Biomedical engineering.;Cellular biology.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 160 p.
  • 总页数 160
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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