Blevins Tracy L, Peterson Sherket B, Lee Elaine L, Bailey Annie M, Frederick Jonathan D, Huynh Thanh N, Gupta Vishal, Grande-Allen K Jane
Department of Bioengineering, Rice University, Houston, Tex 77005, USA.
Cells Tissues Organs. 2008;187(2):113-22. doi: 10.1159/000108582. Epub 2007 Sep 12.
BACKGROUND/AIMS: Because various regions of the mitral valve contain distinctive extracellular matrix enabling the tissues to withstand diverse mechanical environments, we investigated phenotype and matrix production of porcine valvular interstitial cells (VICs) from different regions.
VICswere isolated from the chordae (MCh), the center of the anterior leaflet (AlCtr), and the posterior leaflet free edge (PlFree), then assayed for metabolic, growth, and adhesion rates; collagen and glycosaminoglycan (GAG) production, and phenotype using biochemical assays, flow cytometry, and immunocytochemistry.
The AlCtr VICs exhibited the fastest metabolism but slowest growth. PlFree cells grew the fastest, but demonstrated the least smooth muscle alpha-actin, vimentin, and internal complexity. AlCtr VICs secreted less collagen into the culture medium but more 4-sulfated GAGs than other cells. Adhesion-based separation resulted in altered secretion of sulfated GAGs by MCh and AlCtr cells but not by the PlFree cells.
VICs isolated from various regions of the mitral valve demonstrate phenotypic differences in culture, corresponding to the ability of the mitral valve to accommodate the physical stresses or altered hemodynamics that occur with injury or disease. Further understanding of VIC and valve mechanobiology could lead to novel medical or tissue engineering approaches to treat valve diseases.
背景/目的:由于二尖瓣的不同区域含有独特的细胞外基质,使组织能够承受不同的机械环境,我们研究了来自不同区域的猪瓣膜间质细胞(VICs)的表型和基质产生情况。
从腱索(MCh)、前叶中心(AlCtr)和后叶游离缘(PlFree)分离VICs,然后通过生化分析、流式细胞术和免疫细胞化学检测其代谢、生长和黏附率;胶原蛋白和糖胺聚糖(GAG)的产生以及表型。
AlCtr VICs代谢最快但生长最慢。PlFree细胞生长最快,但平滑肌α-肌动蛋白、波形蛋白和内部复杂性最低。AlCtr VICs向培养基中分泌的胶原蛋白比其他细胞少,但4-硫酸化GAGs更多。基于黏附的分离导致MCh和AlCtr细胞硫酸化GAGs分泌改变,但PlFree细胞未改变。
从二尖瓣不同区域分离的VICs在培养中表现出表型差异,这与二尖瓣适应损伤或疾病时出现的物理应力或改变的血流动力学的能力相对应。对VIC和瓣膜机械生物学的进一步了解可能会带来治疗瓣膜疾病的新医学或组织工程方法。