Investigating the role of substrate stiffness in the persistence of valvular interstitial cell activation.
Investigating the role of substrate stiffness in the persistence of valvular interstitial cell activation.
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DOI：
10.1002/jbm.a.34162
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发表时间：
2012-09
影响因子：
4.9
通讯作者：
Billiar, Kristen L.
中科院分区：
文献类型：
--
作者：
Quinlan, Angela M. Throm;Billiar, Kristen L.
在心脏瓣膜重塑期间和许多疾病状态下，瓣膜间质细胞（VIC）转变为活化的肌成纤维细胞表型，其特征是合成和收缩活性增强。在坚硬基质上培养的 VIC 中也观察到明显的 α 平滑肌肌动蛋白 (αSMA) 阳性应力纤维，这是活化肌成纤维细胞的标志，特别是在存在转化生长因子-β1 (TGF-β1) 的情况下，但硬度与 VIC 表型之间的详细关系尚未探索。本研究的目的是将 VIC 激活表征为各种硬度水平上基底硬度的函数，包括患病瓣膜（僵硬）、正常瓣膜（顺应性）和用于心脏瓣膜组织工程的水凝胶（非常柔软）。从猪主动脉瓣获得的 VIC 在坚硬的组织培养塑料上培养以激活它们，然后在高通量培养系统中在预定硬度的胶原涂层聚丙烯酰胺基质上培养，以评估激活的持久性。从回归分析中提取的定量指标表明，相对于柔顺基质，刚性基质会导致更高的细胞数量、更明显的αSMA正应力纤维表达以及更大的扩散面积，这与之前的研究定性一致。我们的数据还表明，VIC 需要比之前想象的低得多的基材刚度水平才能“停用”它们。 VIC 对基底刚度的高敏感性证明了用于瓣膜修复或工程瓣膜组织的材料的机械性能的重要性。
During heart valve remodeling and in many disease states, valvular interstitial cells (VICs) shift to an activated myofibroblast phenotype characterized by enhanced synthetic and contractile activity. Pronounced alpha smooth muscle actin (αSMA)-positive stress fibers, the hallmark of activated myofibroblasts, are also observed in VICs cultured on stiff substrates especially in the presence of transforming growth factor-beta1 (TGF-β1), yet the detailed relationship between stiffness and VIC phenotype has not been explored. The goal of this study was to characterize VIC activation as a function of substrate stiffness over a wide range of stiffness levels including that of diseased valves (stiff), normal valves (compliant), and hydrogels for heart valve tissue engineering (very soft). VICs obtained from porcine aortic valves were cultured on stiff tissue culture plastic to activate them, then cultured on collagen-coated polyacrylamide substrates of predefined stiffness in a high-throughput culture system to assess the persistence of activation. Quantitative metrics extracted from regression analysis demonstrate that relative to a compliant substrate, stiff substrates result in higher cell numbers, more pronounced expression of αSMA-positive stress fibers, and larger spread area which is in qualitative agreement with previous studies. Our data also indicate that VICs require a much lower substrate stiffness level to “deactivate” them than previously thought. The high sensitivity of VICs to substrate stiffness demonstrates the importance of the mechanical properties of materials used for valve repair or for engineering valve tissue.
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影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D
DOI：
10.1152/ajpheart.01305.2007
发表时间：
2008-04-01
影响因子：
4.8
作者：
Pho, M.;Lee, W.;McCulloch, C. A.
通讯作者：
McCulloch, C. A.
影响因子：
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作者：
Cushing, MC;Liao, JT;Anseth, KS
通讯作者：
Anseth, KS
影响因子：
14
作者：
Kloxin, April M.;Benton, Julie A.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
37.8
作者：
Hoerstrup, SP;Kadner, A;Turina, MI
通讯作者：
Turina, MI