Liu A C, Gotlieb A I
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Histol Histopathol. 2007 Aug;22(8):873-82. doi: 10.14670/HH-22.873.
Valve interstitial cells (VIC) are the most prevalent cells in the heart valve, regulating to a large extent the normal biology of the valve and its pathobiological response to disease. In the process of valve tissue repair by VICs, single cell motility is likely to be important, as it is in wound repair by most mesenchymal type cells. We designed in vitro experiments using low density monolayer cultures to study the association of morphology and motility in single VICs which expressed alpha-smooth muscle actin. We observed that the morphology of single VICs can be categorized into six types which are reminiscent of the shape of VICs seen in vivo during valve repair. Of these morphologies, round, rhomboid, tailed and spindled shaped VICs were the most common. VICs did change their morphology over time. Rhomboid cells could become tailed or spindle-shaped and vice versa. Using time-lapse imaging and immunofluorescent microscopy, we showed that VIC morphologies reflect differences in cell motility and cell-matrix interactions. Tailed and spindle-shaped VICs were the predominant motile types and were associated with few extracellular fibronectin fibrils and less focal adhesions, as demonstrated by vinculin staining. Round and rhomboid shaped VICs were less motile and were associated with prominent vinculin and extracellular fibronectin fibrils. We found that cell mitosis is an important determinant of VIC migration. Many of the motile VICs were associated with mitosis as the daughter cells separated by migrating as tailed and spindle shaped cells. Thus cell morphology is an important determinant of VIC motility.
瓣膜间质细胞（VIC）是心脏瓣膜中最普遍的细胞，在很大程度上调节瓣膜的正常生物学特性及其对疾病的病理生物学反应。在VIC进行瓣膜组织修复的过程中，单细胞运动可能很重要，就像大多数间充质类型细胞进行伤口修复时一样。我们设计了体外实验，使用低密度单层培养来研究表达α-平滑肌肌动蛋白的单个VIC的形态与运动之间的关联。我们观察到单个VIC的形态可分为六种类型，这让人联想到瓣膜修复过程中在体内看到的VIC形状。在这些形态中，圆形、菱形、有尾状和纺锤形的VIC最为常见。VIC确实会随着时间改变其形态。菱形细胞可变成有尾状或纺锤形，反之亦然。通过延时成像和免疫荧光显微镜，我们表明VIC形态反映了细胞运动和细胞-基质相互作用的差异。有尾状和纺锤形的VIC是主要的运动类型，并且如纽蛋白染色所示，它们与细胞外纤连蛋白原纤维较少以及黏着斑较少有关。圆形和菱形的VIC运动性较差，并且与显著的纽蛋白和细胞外纤连蛋白原纤维有关。我们发现细胞有丝分裂是VIC迁移的一个重要决定因素。许多运动性VIC与有丝分裂有关，因为子细胞通过以有尾状和纺锤形细胞的形式迁移而分离。因此，细胞形态是VIC运动性的一个重要决定因素。
