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Evaluation of adult stem cell derived smooth muscle cells for elastic matrix regenerative repair.

机译:评价成人干细胞衍生的平滑肌细胞对弹性基质的再生修复作用。

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摘要

Elastic fibers (EFs), containing elastin protein are the major structural extracellular matrix component of the aorta wall that imparts it stretch and recoil properties. Following injury stimuli to the aorta wall, EFs are disrupted by chronically overexpressed proteolytic enzymes. This leads to loss of wall elasticity, and vessel bulging to form rupture-prone abdominal aortic aneurysms (AAAs). AAA growth arrest or regression to a healthy state requires restoration of elastin homeostasis in the aorta wall which is limited by very poor elastogenicity of adult and aneurysmal vascular smooth muscle cells (SMCs). Based on their purported role in developmental elastogenesis, we explored use of stem cell-derived SMCs in therapeutically augmenting elastogenesis in the AAA wall. In study 1, we differentiated adult rat bone marrow mesenchymal stem cells (BM-MSCs) into SMCs (BM-SMCs), demonstrated their robust capacity for elastin synthesis and significant pro-elastogenic effects on rat aneurysmal SMCs (EaRASMCs). In study 2, we sought to identify phenotypic subtypes of derived BM-SMCs that are most elastogenic. BM-SMCs generated in low glucose (3.1g/L) and high serum (10% v/v) media containing transforming growth factor-beta (TGF&
机译:包含弹性蛋白的弹性纤维(EFs)是主动脉壁的主要结构性细胞外基质成分,赋予其拉伸和反冲特性。在主动脉壁受到损伤刺激后,EFs被慢性过度表达的蛋白水解酶破坏。这导致壁弹性丧失,血管膨胀形成易于破裂的腹主动脉瘤(AAAs)。 AAA生长停滞或恢复到健康状态需要恢复主动脉壁中的弹性蛋白稳态,这受成年和动脉瘤血管平滑肌细胞(SMCs)极差的弹性所限制。基于它们在发育弹性发生中所声称的作用,我们探索了干细胞来源的SMC在AAA壁上在治疗性增强弹性发生中的用途。在研究1中,我们将成年大鼠骨髓间充质干细胞(BM-MSC)分化为SMC(BM-SMC),证明了它们具有强大的弹性蛋白合成能力,并且对大鼠动脉瘤SMC(EaRASMC)具有显着的促弹性生成作用。在研究2中,我们试图确定衍生性最强的BM-SMC的表型亚型。在低葡萄糖(3.1g / L)和高血清(10%v / v)培养基中产生的BM-SMC含有转化生长因子-β(TGF&

著录项

  • 作者

    Swaminathan, Ganesh.;

  • 作者单位

    The University of Akron.;

  • 授予单位 The University of Akron.;
  • 学科 Biomedical engineering.;Biology.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 260 p.
  • 总页数 260
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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