Gupta Vishal, Werdenberg Jennifer A, Blevins Tracy L, Grande-Allen K Jane
Department of Bioengineering, Rice University, Houston, Texas 77251-1892, USA.
Tissue Eng. 2007 Jan;13(1):41-9. doi: 10.1089/ten.2006.0091.
Cells respond to changes in mechanical strains by varying their production of extracellular matrix macromolecules. Because differences in strain patterns between mitral valve leaflets and chordae tendineae have been linked to different quantities and types of glycosaminoglycans (GAGs), we investigated the effects of various strain conditions on GAG synthesis by valvular interstitial cells (VICs) using an in vitro 3-dimensional tissue-engineering model. VICs from leaflets or chordae were seeded within collagen gels and subjected to uniaxial or biaxial static tension for 1 week. GAGs synthesized within the collagen gels and secreted into the surrounding medium were analyzed using fluorophore-assisted carbohydrate electrophoresis. In constrained conditions, more 4-sulfated GAGs were retained within the collagen gel, whereas more hyaluronan was secreted into the surrounding medium. Selected GAG classes were found in significantly different proportions in collagen gels seeded with leaflet cells versus chordal cells. The only significant difference between uniaxial and biaxial regions was found for 6-sulfated GAGs in the gels seeded with chordal cells (p<0.05). This study suggests how mechanical loading may influence GAG production and localization in the remodeling of the mitral valve and has design implications for engineered tissues.
细胞通过改变细胞外基质大分子的产生来响应机械应变的变化。由于二尖瓣小叶和腱索之间的应变模式差异与不同数量和类型的糖胺聚糖（GAG）有关，我们使用体外三维组织工程模型研究了各种应变条件对瓣膜间质细胞（VIC）合成GAG的影响。将来自小叶或腱索的VIC接种在胶原凝胶中，并进行单轴或双轴静态拉伸1周。使用荧光团辅助碳水化合物电泳分析胶原凝胶内合成并分泌到周围培养基中的GAG。在受限条件下，更多的4-硫酸化GAG保留在胶原凝胶中，而更多的透明质酸分泌到周围培养基中。在接种小叶细胞与腱索细胞的胶原凝胶中，选定的GAG类别以显著不同的比例被发现。在接种腱索细胞的凝胶中，单轴和双轴区域之间的唯一显著差异是6-硫酸化GAG（p<0.05）。这项研究表明了机械负荷如何影响二尖瓣重塑过程中GAG的产生和定位，并对工程组织的设计具有启示意义。
