Yin Yijun, Que Jianwen, Teh Ming, Cao Wei Ping, El Oakley Reida Menshawe, Lim Sai-Kiang
Department of Obstetrics and Gynaecology, National University of Singapore.
Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):691-6. doi: 10.1161/01.ATV.0000120375.51196.73. Epub 2004 Feb 5.
Endothelial differentiation is a fundamental process in angiogenesis and vasculogenesis with implications in development, normal physiology, and pathology. To better understand this process, an in vitro cellular system that recapitulates endothelial differentiation and is amenable to experimental manipulations is required.
Embryonic cell lines that differentiate exclusively into endothelial cells were derived from early mouse embryos using empirical but reproducible culture techniques without viral or chemical transformation. The cells were not pluripotent and expressed reduced levels of Oct 4 and Rex-1. They were non-tumorigenic with a population doubling time of approximately 15 hours. When plated on matrigel, they readily differentiated to form patent tubular structures with diameters of 30 to 150 microm. The differentiated cells endocytosed acetylated low-density lipoprotein (LDL) and began to express endothelial-specific markers such as CD34, CD31, Flk-1, TIE2, P-selectin, Sca-1, and thy-1. They also expressed genes essential for differentiation and maintenance of endothelial lineages, eg, Flk-1, vascular endothelial growth factor (VEGF), and angiopoietin-1. When transplanted into animal models, these cells incorporated into host vasculature.
These cell lines can undergo in vitro and in vivo endothelial differentiation that recapitulated known endothelial differentiation pathways. Therefore, they are ideal for establishing an in vitro cellular system to study endothelial differentiation.
内皮细胞分化是血管生成和血管发生中的一个基本过程，对发育、正常生理和病理过程均有影响。为了更好地理解这一过程，需要一个能够概括内皮细胞分化且适合进行实验操作的体外细胞系统。
使用经验性但可重复的培养技术，从早期小鼠胚胎中获得了仅分化为内皮细胞的胚胎细胞系，无需病毒或化学转化。这些细胞并非多能性细胞，Oct 4和Rex-1的表达水平降低。它们无致瘤性，群体倍增时间约为15小时。接种到基质胶上时，它们很容易分化形成直径为30至150微米的有腔管状结构。分化后的细胞能够内吞乙酰化低密度脂蛋白（LDL），并开始表达内皮细胞特异性标志物，如CD34、CD31、Flk-1、TIE2、P-选择素、Sca-1和thy-1。它们还表达了内皮细胞谱系分化和维持所必需的基因，如Flk-1、血管内皮生长因子（VEGF）和血管生成素-1。将这些细胞移植到动物模型中时，它们能够整合到宿主脉管系统中。
这些细胞系能够在体外和体内进行内皮细胞分化，重现已知的内皮细胞分化途径。因此，它们是建立体外细胞系统以研究内皮细胞分化的理想选择。
