Differences in tissue-remodeling potential of aortic and pulmonary heart valve interstitial cells
Differences in tissue-remodeling potential of aortic and pulmonary heart valve interstitial cells
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DOI：
10.1089/ten.2006.0324
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发表时间：
2007-09-01
影响因子：
--
通讯作者：
Sacks, Michael S.
中科院分区：
文献类型：
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作者：
Merryman, W. David;Liao, Jun;Sacks, Michael S.
心脏瓣膜间质细胞（VICs）似乎具有动态和可逆的表型，这一属性推测是瓣膜组织在发育和修复期间重塑所必需的。因此，我们假设，以平滑肌α -肌动蛋白为主的主动脉和肺动脉VICs（分别为AVICs和PVICs）的细胞骨架（CSK）重塑能力在植入胶原凝胶后会表现出独特的收缩行为。使用猪细胞源，我们观察到VIC群体在早期时间点（2和4小时）不像真皮成纤维细胞那样收缩凝胶，但在收缩之前形成了一个中心细胞簇。聚集后，vic似乎从凝胶的中心向外辐射，而成纤维细胞不迁移，而是局部收缩凝胶。转化生长因子β 1处理的VIC凝胶迅速收缩，显示出对细胞因子相似的敏感性。此外，我们通过原子力显微镜比较AVIC和PVIC的刚度来评估底层CSK的初始力学状态。AVICs不仅明显比PVICs更硬（p < 0.001），而且在24和48小时时，AVICs的凝胶收缩也明显更大（p < 0.001）。综上所述，这些发现表明AVICs能够诱导更大的细胞外基质收缩，可能表现为更明显的瓣膜组织重塑能力。此外，AVICs和PVICs之间存在着显著的机械生物学差异，这可能对理解原生瓣膜组织重塑具有重要意义。阐明这些差异也将定义心脏瓣膜修复和置换的组织工程方法发展中的重要功能终点。
Heart valve interstitial cells (VICs) appear to have a dynamic and reversible phenotype, an attribute speculated to be necessary for valve tissue remodeling during times of development and repair. Therefore, we hypothesized that the cytoskeletal (CSK) remodeling capability of the aortic and pulmonary VICs (AVICs and PVICs, respectively), which are dominated by smooth muscle alpha-actin, would exhibit unique contractile behaviors when seeded on collagen gels. Using a porcine cell source, we observed that VIC populations did not contract the gels at early time points (2 and 4 hours) as dermal fibroblasts did, but formed a central cluster of cells prior to contraction. After clustering, VICs appeared to radiate out from the center of the gels, whereas fibroblasts did not migrate but contracted the gels locally. VIC gels treated with transforming growth factor beta 1 contracted the gels rapidly, revealing similar sensitivity to the cytokine. Moreover, we evaluated the initial mechanical state of the underlying CSK by comparing AVIC and PVIC stiffness with atomic force microscopy. Not only were AVICs significantly stiffer (p < 0.001) than the PVICs, but they also contracted the gels significantly more at 24 and 48 hours (p < 0.001). Taken together, these findings suggest that the AVICs are capable of inducing greater extra cellular matrix contraction, possibly manifesting in a more pronounced ability to remodel valvular tissues. Moreover, significant mechanobiological differences between AVICs and PVICs exist, and may have implications for understanding native valvular tissue remodeling. Elucidating these differences will also define important functional endpoints in the development of tissue engineering approaches for heart valve repair and replacement.