Gendron R L, Tsai F Y, Paradis H, Arceci R J
Department of Pediatrics, Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio, 45229-3039, USA.
Dev Biol. 1996 Jul 10;177(1):332-46. doi: 10.1006/dbio.1996.0167.
The de novo formation of blood vessels (vasculogenesis) is an integral part of embryogenesis. Elucidation of the role of cytokine cooperation in vasculogenesis may lead to a better understanding of organogenesis, blood vessel regulation during tumorigenesis, and tissue injury. We have used embryonic stem cells to derive an endothelial cell line, designated IEM, which expresses a range of endothelial markers, including Von Willibrand Factor VIII related antigen, vascular cell adhesion molecule, platelet-endothelial cell adhesion molecule (CD31), and receptors for acetylated low-density lipoprotein. More importantly, IEM cells can be induced upon exposure to combinations of basic fibroblast growth factor and leukemia inhibitory factor (LIF) to proliferate and undergo vasculogenesis in vitro, resulting in the formation of vascular tubes and microcapillary anastomoses. Moreover, exposure to both cytokines conditionally permits IEM cells to specifically chimerize microvascular endothelium in vivo following blastocyst injection. These results indicate that bFGF and LIF together contribute to the induction and support of embryonic vasculogenesis in an isolated endothelial cell line. Our results provide evidence that combined actions of bFGF/LIF may play a role in mechanisms controlling blood vessel development.
血管的从头形成（血管发生）是胚胎发生的一个组成部分。阐明细胞因子协同作用在血管发生中的作用可能有助于更好地理解器官发生、肿瘤发生过程中的血管调节以及组织损伤。我们利用胚胎干细胞衍生出一种内皮细胞系，命名为IEM，它表达一系列内皮标志物，包括血管性血友病因子VIII相关抗原、血管细胞黏附分子、血小板内皮细胞黏附分子（CD31）以及乙酰化低密度脂蛋白受体。更重要的是，IEM细胞在暴露于碱性成纤维细胞生长因子和白血病抑制因子（LIF）的组合时可被诱导在体外增殖并进行血管发生，从而形成血管管和微血管吻合。此外，在囊胚注射后，暴露于这两种细胞因子可使IEM细胞在体内特异性地嵌合微血管内皮。这些结果表明，bFGF和LIF共同促成了在分离的内皮细胞系中胚胎血管发生的诱导和支持。我们的结果提供了证据，表明bFGF/LIF的联合作用可能在控制血管发育的机制中发挥作用。
