Endothelial cells derived from human embryonic stem cells

Endothelial cells derived from human embryonic stem cells
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DOI:
10.1073/pnas.032074999
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发表时间:
2002-04-02
影响因子:
11.1
通讯作者:
Langer, R
Langer, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Levenberg, S;Golub, JS;Langer, R

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人类胚胎干细胞具有分化成各种细胞类型的潜力,因此可能是移植或组织工程中有用的细胞来源。我们在这里描述了人类胚胎干细胞分化成内皮细胞形成血管样结构的步骤。采用血小板内皮细胞粘附分子-1(血小板内皮细胞粘附分子-1)抗体分离人胚胎源性内皮细胞,在体外和体内对其行为进行表征,并探讨其在组织工程中的应用潜力。我们发现,分离的胚胎PECAM1+细胞,在培养中生长,显示出类似血管内皮的特征。这些细胞表达内皮细胞标志物的模式与人脐静脉内皮细胞相似,它们的连接组织正确,并且它们具有乙酰化低密度脂蛋白的高代谢。此外,在基质上培养时,细胞能够分化并形成管状结构。在体内,当移植到SCID小鼠体内时,细胞似乎形成了含有小鼠血细胞的微血管。通过进一步的研究,这些细胞可以提供人类内皮细胞的来源,这可能有利于潜在的应用,如工程新血管,内皮细胞移植到心脏进行心肌再生,以及诱导血管生成治疗局部缺血。
Human embryonic stem cells have the potential to differentiate into various cell types and, thus, may be useful as a source of cells for transplantation or tissue engineering. We describe here the differentiation steps of human embryonic stem cells into endothelial cells forming vascular-like structures. The human embryonic-derived endothelial cells were isolated by using platelet endothelial cell-adhesion molecule-1 (PECAM1) antibodies, their behavior was characterized in vitro and in vivo, and their potential in tissue engineering was examined. We show that the isolated embryonic PECAM1+ cells, grown in culture, display characteristics similar to vessel endothelium. The cells express endothelial cell markers in a pattern similar to human umbilical vein endothelial cells, their junctions are correctly organized, and they have high metabolism of acetylated low-density lipoprotein. In addition, the cells are able to differentiate and form tube-like structures when cultured on matrigel, In vivo, when transplanted into SCID mice, the cells appeared to form microvessels containing mouse blood cells. With further studies, these cells could provide a source of human endothelial cells that could be beneficial for potential applications such as engineering new blood vessels, endothelial cell transplantation into the heart for myocardial regeneration, and induction of angiogenesis for treatment of regional ischemia.