Functional vascular endothelium derived from human induced pluripotent stem cells.
Functional vascular endothelium derived from human induced pluripotent stem cells.
复制标题
DOI：
10.1016/j.stemcr.2013.06.007
复制
发表时间：
2013
影响因子：
5.9
通讯作者：
Garcia-Cardena, Guillermo
中科院分区：
文献类型：
--
作者：
Adams, William J.;Zhang, Yuzhi;Cloutier, Jennifer;Kuchimanchi, Pranati;Newton, Gail;Sehrawat, Seema;Aird, William C.;Mayadas, Tanya N.;Luscinskas, Francis W.;Garcia-Cardena, Guillermo
血管内皮是一个动态的细胞界面，显示出独特的表型可塑性。这种可塑性对血管功能至关重要，并且当失调时在几种疾病中是致病的。内皮细胞的人类基因型-表型研究受到患者特异性内皮细胞不可用性的限制。为了建立用于研究内皮生物学的细胞平台，我们已经从人诱导多能干细胞（iPSC）产生了血管内皮，其表现出成熟的原代血管内皮的丰富的功能表型可塑性。这些内皮细胞对不同的促炎刺激作出反应，采用活化的表型，包括白细胞粘附分子表达、细胞因子产生和支持白细胞迁移。它们保持响应多种血管渗透性因素的动态屏障特性。重要的是，生物力学或药理学刺激可以诱导病理生理相关的动脉粥样硬化保护或atheroprone表型。我们的研究结果表明，iPSC衍生的内皮细胞具有功能表型可塑性的库，并适合于基于细胞的检测，探测内皮细胞对炎症和心血管疾病的贡献。人iPSC产生具有丰富功能库的血管EC iPSC-EC可经历内皮活化并维持动态渗透性生物力学力将iPSC-EC引导至动脉粥样硬化保护或动脉粥样硬化酮表型iPSC-EC经由药理学刺激被引导至动脉粥样硬化保护表型
Vascular endothelium is a dynamic cellular interface that displays a unique phenotypic plasticity. This plasticity is critical for vascular function and when dysregulated is pathogenic in several diseases. Human genotype-phenotype studies of endothelium are limited by the unavailability of patient-specific endothelial cells. To establish a cellular platform for studying endothelial biology, we have generated vascular endothelium from human induced pluripotent stem cells (iPSCs) exhibiting the rich functional phenotypic plasticity of mature primary vascular endothelium. These endothelial cells respond to diverse proinflammatory stimuli, adopting an activated phenotype including leukocyte adhesion molecule expression, cytokine production, and support for leukocyte transmigration. They maintain dynamic barrier properties responsive to multiple vascular permeability factors. Importantly, biomechanical or pharmacological stimuli can induce pathophysiologically relevant atheroprotective or atheroprone phenotypes. Our results demonstrate that iPSC-derived endothelium possesses a repertoire of functional phenotypic plasticity and is amenable to cell-based assays probing endothelial contributions to inflammatory and cardiovascular diseases. Human iPSCs generate vascular ECs with a rich functional repertoire iPSC-ECs can undergo endothelial activation and maintain dynamic permeability Biomechanical forces direct iPSC-ECs to atheroprotective or atheroprone phenotypes iPSC-ECs are directed to an atheroprotective phenotype via pharmacological stimulus
登录
查看更多内容
DOI：
10.1016/j.carpath.2012.06.006
发表时间：
2013-01
期刊：
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
影响因子：
--
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
DOI：
10.1161/atvbaha.111.230938
发表时间：
2011-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Rufaihah AJ;Huang NF;Jamé S;Lee JC;Nguyen HN;Byers B;De A;Okogbaa J;Rollins M;Reijo-Pera R;Gambhir SS;Cooke JP
通讯作者：
Cooke JP
影响因子：
15.9
作者：
Parmar, KM;Larman, HB;Garcia-Cardeña, G
通讯作者：
Garcia-Cardeña, G
影响因子：
33.6
作者：
Chiu JJ;Chien S
通讯作者：
Chien S
DOI：
10.1038/nrm2596
发表时间：
2009-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--