Early embryonic blood vessels are typically composed of fragile tubes of endothelial cells encircled by vascular smooth muscle cells. Early human vasculogenesis was explored in spontaneous and directed differentiation models derived from human embryonic stem (HES) cells. In a 3-dimensional (3D) model, HES cells were studied for their potential for vascular differentiation during the spontaneous formation of embryoid bodies. Directed differentiation was investigated by means of a 2-dimensional (2D) differentiation method to promote vascular differentiation from HES cells (without the formation of embryoid bodies). Using this latter approach, up-regulation of early lineage markers of endothelial progenitors were induced. Additional culture under strict conditions and exposure to angiogenic growth factors resulted in a prolonged differentiation pathway into mature endothelial cells and up-regulation of vascular smooth muscle cell markers. The use of 3D collagen gels and Matrigel assays for the induction and inhibition of human vascular sprouting in vitro further established the vascular potential of the cells generated by the 2D differentiation system. Our study shows that HES cells can provide useful models to study early differentiation and development of blood vessels. Moreover, the 2D differentiation model facilitates both the production of vascular lineage cells from HES cells for various potential therapeutic applications and also provides a model for studying the mechanisms involved in early human embryonic blood vessel development.

中文翻译：

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人类胚胎干细胞作为人类血管发育和血管分化诱导的体外模型。

早期胚胎血管通常由脆弱的内皮细胞管组成，周围环绕着血管平滑肌细胞。在源自人类胚胎干 (HES) 细胞的自发和定向分化模型中探索了早期人类血管生成。在 3 维 (3D) 模型中，研究了 HES 细胞在胚状体自发形成过程中血管分化的潜力。通过二维 (2D) 分化方法研究定向分化，以促进 HES 细胞的血管分化（不形成胚状体）。使用后一种方法，诱导了内皮祖细胞早期谱系标志物的上调。在严格条件下进行的额外培养和暴露于血管生成生长因子会导致分化为成熟内皮细胞的途径延长和血管平滑肌细胞标记物的上调。使用 3D 胶原凝胶和 Matrigel 测定法在体外诱导和抑制人血管发芽，进一步确定了 2D 分化系统产生的细胞的血管潜能。我们的研究表明，HES 细胞可以为研究血管的早期分化和发育提供有用的模型。此外，2D 分化模型有助于从 HES 细胞产生血管谱系细胞以用于各种潜在的治疗应用，还为研究早期人类胚胎血管发育所涉及的机制提供了一个模型。