Lang Ingrid, Schweizer Angela, Hiden Ursula, Ghaffari-Tabrizi Nassim, Hagendorfer Gabriele, Bilban Martin, Pabst Maria A, Korgun Emin T, Dohr Gottfried, Desoye Gernot
Institute of Cell Biology, Histology and Embryology, Center of Molecular Medicine, Medical University of Graz, Graz 8010, Austria.
Differentiation. 2008 Dec;76(10):1031-43. doi: 10.1111/j.1432-0436.2008.00302.x. Epub 2008 Jul 30.
Growing interest in the sources of origin of blood vessel related diseases has led to an increasing knowledge about the heterogeneity and plasticity of endothelial cells lining arteries and veins. So far, most of these studies were performed on animal models. Here, we hypothesized that the plasticity of human fetal endothelial cells depends on their vascular bed of origin i.e. vein or artery and further that the differences between arterial and venous endothelial cells would extend to phenotype and genotype. We established a method for the isolation of fetal arterial and venous endothelial cells from the human placenta and studied the characteristics of both cell types. Human placental arterial endothelial cells (HPAEC) and human placental venous endothelial cells (HPVEC) express classical endothelial markers and differ in their phenotypic, genotypic, and functional characteristics: HPAEC are polygonal cells with a smooth surface growing in loose arrangements and forming monolayers with classical endothelial cobblestone morphology. They express artery-related genes (hey-2, connexin 40, depp) and more endothelial-associated genes than HPVEC. Functional testing demonstrated that vascular endothelial growth factors (VEGFs) induce a higher proliferative response on HPAEC, whereas placental growth factors (PlGFs) are only effective on HPVEC. HPVEC are spindle-shaped cells with numerous microvilli at their surface. They grow closely apposed to each other, form fibroblastoid swirling patterns at confluence and have shorter generation and population doubling times than HPAEC. HPVEC overexpress development-associated genes (gremlin, mesenchyme homeobox 2, stem cell protein DSC54) and show an enhanced differentiation potential into adipocytes and osteoblasts in contrast to HPAEC. These data provide collective evidence for a juvenile venous and a more mature arterial phenotype of human fetal endothelial cells. The high plasticity of the fetal venous endothelial cells may reflect their role as tissue-resident endothelial progenitors during embryonic development with a possible benefit for regenerative cell therapy.
对血管相关疾病起源的兴趣日益浓厚，使得人们对动脉和静脉内衬的内皮细胞的异质性和可塑性有了越来越多的了解。到目前为止，这些研究大多是在动物模型上进行的。在此，我们假设人类胎儿内皮细胞的可塑性取决于其起源的血管床，即静脉或动脉，并且进一步认为动脉和静脉内皮细胞之间的差异会延伸到表型和基因型。我们建立了一种从人胎盘中分离胎儿动脉和静脉内皮细胞的方法，并研究了这两种细胞类型的特征。人胎盘动脉内皮细胞（HPAEC）和人胎盘静脉内皮细胞（HPVEC）表达经典的内皮标志物，并且在表型、基因型和功能特征上存在差异：HPAEC是多边形细胞，表面光滑，呈松散排列生长，形成具有经典内皮鹅卵石形态的单层细胞。它们表达与动脉相关的基因（hey - 2、连接蛋白40、depp），并且比HPVEC表达更多的内皮相关基因。功能测试表明，血管内皮生长因子（VEGFs）对HPAEC诱导更高的增殖反应，而胎盘生长因子（PlGFs）仅对HPVEC有效。HPVEC是纺锤形细胞，表面有许多微绒毛。它们彼此紧密相邻生长，在汇合时形成成纤维细胞样漩涡模式，并且比HPAEC具有更短的代时和群体倍增时间。与HPAEC相比，HPVEC过表达与发育相关的基因（gremlin、间充质同源盒2、干细胞蛋白DSC54），并显示出向脂肪细胞和成骨细胞的增强分化潜能。这些数据为人类胎儿内皮细胞的幼稚静脉表型和更成熟的动脉表型提供了综合证据。胎儿静脉内皮细胞的高可塑性可能反映了它们在胚胎发育过程中作为组织驻留内皮祖细胞的作用，这可能对再生细胞治疗有益。
