Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle-like cells and form vascular networks in vivo
Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle-like cells and form vascular networks in vivo
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DOI：
10.1161/circresaha.107.150201
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发表时间：
2007-08-03
影响因子：
20.1
通讯作者：
Langer, Robert
中科院分区：
文献类型：
--
作者：
Ferreira, Lino S.;Gerecht, Sharon;Langer, Robert
我们报告说，人胚胎干细胞含有血管祖细胞，有能力分化成内皮样细胞和平滑肌（SM）样细胞的人口。从悬浮培养10天的EB中分离血管祖细胞，并通过表达内皮/造血标记物CD 34（CD 34（+）细胞）进行表征。当这些细胞随后在EGM-2中培养时（内皮生长培养基）补充血管内皮生长因子-165（50 ng/mL）时，它们产生以鹅卵石细胞形态为特征的内皮样细胞，表达内皮标志物（血小板内皮细胞粘附分子-1，CD 34，KDR/Flk-1，血管内皮钙粘蛋白，血管性血友病因子），乙酰化低密度脂蛋白的掺入，以及当置于基质胶中时形成毛细血管样结构。相反，当CD 34（+）细胞在补充有血小板衍生生长因子-BB的EGM-2中培养时，（50 ng/mL）时，它们产生SM样细胞，其特征在于梭形形态、SM细胞标志物的表达、（α-SM肌动蛋白、SM肌球蛋白重链、钙调蛋白、钙调蛋白、SM α-22），以及响应于普通药理学试剂如卡巴胆碱和阿托品而收缩和舒张的能力，但当置于基质胶中时很少形成毛细血管样结构。在裸鼠中的植入研究表明，两种细胞类型都有助于人类微血管的形成。一些微血管含有小鼠血细胞，这表明与宿主血管系统的功能整合。因此，利用本研究建立的方法从人胚胎干细胞中分离血管祖细胞，可以为研究内皮细胞和平滑肌细胞的发育机制提供一种手段，也可以为血管组织工程提供潜在的细胞来源。
We report that human embryonic stem cells contain a population of vascular progenitor cells that have the ability to differentiate into endothelial-like and smooth muscle (SM)-like cells. Vascular progenitor cells were isolated from EBs grown in suspension for 10 days and were characterized by expression of the endothelial/hematopoietic marker CD34 (CD34(+) cells). When these cells are subsequently cultured in EGM-2 (endothelial growth medium) supplemented with vascular endothelial growth factor-165 (50 ng/mL), they give rise to endothelial-like cells characterized by a cobblestone cell morphology, expression of endothelial markers (platelet endothelial cell-adhesion molecule-1, CD34, KDR/Flk-1, vascular endothelial cadherin, von Willebrand factor), incorporation of acetylated low-density lipoprotein, and formation of capillary-like structures when placed in Matrigel. In contrast, when CD34(+) cells are cultured in EGM-2 supplemented with platelet-derived growth factor-BB (50 ng/mL), they give rise to SM-like cells characterized by spindle-shape morphology, expression of SM cell markers (alpha-SM actin, SM myosin heavy chain, calponin, caldesmon, SM alpha-22), and the ability to contract and relax in response to common pharmacological agents such as carbachol and atropine but rarely form capillary-like structures when placed in Matrigel. Implantation studies in nude mice show that both cell types contribute to the formation of human microvasculature. Some microvessels contained mouse blood cells, which indicates functional integration with host vasculature. Therefore, the vascular progenitors isolated from human embryonic stem cells using methods established in the present study could provide a means to examine the mechanisms of endothelial and SM cell development, and they could also provide a potential source of cells for vascular tissue engineering.