在一项新的研究中，来自美国哈佛干细胞研究所的研究人员成功地将人诱导性多能干细胞(inducedpluripotent stem cells，iPSCs)转化为血管内皮细胞(vascularendothelial cells)，并详细地揭示出这些细胞如何发挥功能。利用一种独特的方法，他们在iPSCs来源的模拟血液流动的血管内皮表面上施加机械力可诱导血管内皮细胞分化为特定类型的细胞。比如，感觉到更强血液流动的血管内皮细胞变成动脉细胞，而那些感觉到较弱血液流动的血管内皮细胞变成静脉细胞。相关研究结果于2013年7月25日发表在美国权威学术期刊《Stem CellReports 干细胞报告》上。
论文通信作者Guillermo García-Cardena博士说，“对我们而言，发现这些细胞对生物机械信号作出反应是特别激动人心的。通过让细胞接触‘动脉粥样硬化易发性血液流动(atheroprone flow)’，我们能够让这些细胞直接分化为血液循环系统中受到诸如动脉粥样硬化之类的疾病影响的区域内的细胞。”如今，García-Cardena正在利用源自人iPSCs的血管内皮细胞构建动脉斑块形成的模型，并鉴定可能阻止斑块形成潜在药物。
García-Cardena研究团队发现源自人iPSCs的血管内皮细胞通过形成体内的成熟内皮组织而表现出三种关键性的功能：产生炎症反应、阻止血液从血管中泄露以及阻止血栓形成。
基于这些信息，García-Cardena的研究也产生另一种激动人心的影响：它可能潜在地降低甚至消除在肾脏透析和肺衰竭治疗期间对肝素使用的需求，从而使得这两种疗法更加安全。
尽管肝素能够高效地阻止血栓形成，但是它也能导致失血、内出血和干扰愈合过程。García-Carden说，“源自人iPSCs的血管内皮细胞作为一种抗凝剂能够很好地发挥作用，而不需要定期地接受肝素注射。”
利用诱导性多能干细胞培育出功能性血管内皮细胞，无疑更加拓展了干细胞的医用领域，为动脉粥样硬化、肺衰竭等疾病的患者带来了治愈的希望。
推荐原文阅读：
Stem Cell Reports. 2013 Jul 25;1(2):105-13. doi: 10.1016/j.stemcr.2013.06.007.
Functional vascular endothelium derived from human induced pluripotent stem cells.
Adams WJ, Zhang Y, Cloutier J, Kuchimanchi P, Newton G, Sehrawat S, Aird WC, Mayadas TN, Luscinskas FW, García-Carde?a G.
Source
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA ; Program in Developmental and Regenerative Biology, Harvard Medical School, Boston, MA 02115, USA ; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Abstract
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 humaninduced pluripotent stem cells (iPSCs) exhibiting the rich functional phenotypic plasticity of mature primary vascular endothelium. These endothelialcells 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.
