Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies.
Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies.
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发表时间：
1988-03
期刊：
影响因子：
4.6
通讯作者：
W. Risau;H. Sariola;H. Zerwes;J. Sasse;P. Ekblom;R. Kemler;T. Doetschman
中科院分区：
文献类型：
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作者：
W. Risau;H. Sariola;H. Zerwes;J. Sasse;P. Ekblom;R. Kemler;T. Doetschman
胚胎干细胞（ESC）先前已从小鼠囊胚的内细胞群细胞中建立。在悬浮培养中，它们自发分化为含血岛囊性胚状体（CEB）。通过向同基因小鼠腹腔注射ESC，诱导原位分化的血岛内皮细胞形成血管，这一过程称为血管生成。在腹膜中，发生了血岛的融合和体内样初级毛细血管丛的形成。将ESC、ESC衍生复合物和囊性胚样体（ESC- ceb）移植到鹌鹑绒毛尿囊膜（CAM）上，可诱导非卵黄囊内胚层结构引导的血管生成反应。ESC-CEB卵黄囊内胚层和正常小鼠卵黄囊组织均未诱导鹌鹑CAM血管生成。ESC-CEB提取物在体外刺激毛细血管内皮细胞增殖。在体外培养和分化过程中，有丝分裂活性增加。几乎所有的生长因子活性都与细胞有关。ESC-CEB衍生的内皮细胞生长因子与肝素-sepharose结合。通过免疫印迹实验，对酸性和碱性纤维母细胞生长因子（FGF）进行抗体鉴定，确定了肝素-磷酸酶纯化材料中的酸性纤维母细胞生长因子（FGF）。我们得出结论，血管发生，即血管从原位分化的内皮细胞发育而来，血管发生，即毛细血管从先前存在的血管中发芽，是胚胎发生过程中非常早期的事件，可以通过体外ESC分化来研究。我们的研究结果表明，血管生成和血管生成受到不同的调控。
Embryonic stem cells (ESC) have been established previously from the inner cell mass cells of mouse blastocysts. In suspension culture, they spontaneously differentiate to blood-island-containing cystic embryoid bodies (CEB). The development of blood vessels from in situ differentiating endothelial cells of blood islands, a process which we call vasculogenesis, was induced by injecting ESC into the peritoneal cavity of syngeneic mice. In the peritoneum, fusion of blood islands and formation of an in vivo-like primary capillary plexus occurred. Transplantation of ESC and ESC-derived complex and cystic embryoid bodies (ESC-CEB) onto the quail chorioallantoic membrane (CAM) induced an angiogenic response, which was directed by nonyolk sac endoderm structures. Neither yolk sac endoderm from ESC-CEB nor normal mouse yolk sac tissue induced angiogenesis on the quail CAM. Extracts from ESC-CEB stimulated the proliferation of capillary endothelial cells in vitro. Mitogenic activity increase during in vitro culture and differentiation of ESC. Almost all growth factor activity was associated with the cells. The ESC-CEB derived endothelial cell growth factor bound to heparin-sepharose. The identification of acidic fibroblast growth factor (FGF)in heparin-sepharose-purified material was accomplished by immunoblot experiments involving antibodies against acidic and basic FGF. We conclude that vasculogenesis, the development of blood vessels from in situ differentiating endothelial cells, and angiogenesis, the sprouting of capillaries from preexisting vessels are very early events during embryogenesis which can be studied using ESC differentiating in vitro. Our results suggest that vasculogenesis and angiogenesis are differently regulated.