Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to vascular endothelial growth factor-A and transforming growth factor-β2
Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to vascular endothelial growth factor-A and transforming growth factor-β2
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DOI：
10.1161/01.res.0000245188.41002.2c
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发表时间：
2006-10-13
影响因子：
20.1
通讯作者：
Bischoff, Joyce
中科院分区：
文献类型：
--
作者：
Paruchuri, Sailaja;Yang, Jeong-Hee;Bischoff, Joyce
胎儿半月瓣小叶的原位分析显示，细胞共表达内皮和间充质标记物，沿着内皮，在成人瓣膜中观察到的频率降低。为了确定这些细胞是否是祖细胞，我们从人肺动脉瓣中分离克隆群。克隆表达内皮标记物，但显示出响应血管内皮生长因子（VEGF）-A进一步分化为内皮的潜力。当暴露于转化生长因子（TGF）-β（2）时，单个克隆在不同程度上采用了间充质表型，并表达了内皮细胞向间充质转化（EMT）的标志物。VEGF和TGF β 2诱导的表型变化都是部分可逆的，表明这些细胞具有可塑性。当用VEGF或TGF β（2）攻击时，在克隆群体中可以看到内皮/间充质潜能的层次：最初接近内皮表型的细胞显示出对TGF β（2）的强烈反应，这可以被VEGF抑制，而接近间充质表型的细胞对TGF β（2）有反应，但对VEGF的内皮诱导作用有抵抗力。这些发现表明存在双能瓣膜祖细胞，其具有分化为瓣叶内皮细胞或间质细胞的能力。了解这些细胞的分化潜力和功能对于理解心脏瓣膜疾病可能是重要的，并且也可以应用于当前创建组织工程心脏瓣膜的范例。
In situ analysis of fetal semilunar valve leaflets has revealed cells coexpressing endothelial and mesenchymal markers along the endothelium, with diminished frequency seen in adult valves. To determine whether such cells are progenitor cells, we isolated clonal populations from human pulmonary valves. The clones expressed endothelial markers but showed potential to further differentiate into endothelium in response to vascular endothelial growth factor (VEGF)-A. When exposed to transforming growth factor (TGF)-beta(2), individual clones adopted a mesenchymal phenotype to varying degrees and expressed markers of endothelial to mesenchymal transformation (EMT). Both VEGF- and TGF beta(2)-induced phenotypic changes were partially reversible, indicating the plasticity of these cells. When challenged with VEGF or TGF beta(2), a hierarchy of endothelial/mesenchymal potential could be seen among the clonal populations: cells initially closer to an endothelial phenotype showed a strong response to TGF beta(2) that could be inhibited by VEGF, whereas cells closer to a mesenchymal phenotype responded to TGF beta(2) but were resistant to endothelial-inducing effects of VEGF. These findings suggest the presence of bipotential valve progenitor cells with ability to differentiate into either endothelial or interstitial cells of the valve leaflet. Understanding the differentiation potential and function of these cells may be important for understanding heart valve disease and may also be applied to current paradigms for creating tissue-engineered heart valves.