Human induced pluripotent stem cells derived endothelial cells mimicking vascular inflammatory response under flow.
Human induced pluripotent stem cells derived endothelial cells mimicking vascular inflammatory response under flow.
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DOI：
10.1063/1.4940041
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发表时间：
2016-01
期刊：
影响因子：
3.2
通讯作者：
Li Wang;Meng Xiang;Yingying Liu;N. Sun;Meng Lu;Yang Shi;Xinhong Wang;Dan Meng;Sifen chen;J. Qin
中科院分区：
文献类型：
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作者：
Li Wang;Meng Xiang;Yingying Liu;N. Sun;Meng Lu;Yang Shi;Xinhong Wang;Dan Meng;Sifen chen;J. Qin
内皮细胞在血管疾病研究和再生医学中具有巨大的应用潜力。自体的人EC难以在体外获得足够数量，而人诱导多能干细胞（iPSC）为产生用于这些目的的EC提供了独特的机会。在这项工作中，我们提出了一种新的和有效的方法来简单地将人类iPSCs分化为功能性EC，这些EC可以在制造的微型装置上对生理水平的流动和炎症刺激做出反应。根据诱导发育原理，仅一周内即可从人iPSC分化出内皮样细胞。内皮祖细胞和内皮标志物基因（GATA 2，RUNX 1，CD 34和CD 31）的表达在初始诱导过程后的第二天和第四天增加。分化的EC表现出细胞特异性标记物（CD 31和血管性血友病因子抗体）的强表达，与人脐静脉内皮细胞中存在的标记物相似。此外，hiPSC衍生的EC能够形成管状结构并响应于在微型装置上产生的血管样流动。此外，经肿瘤坏死因子（TNF-α）预处理的人诱导多能干细胞-内皮细胞（hiPSC-ECs）在流动条件下对人单核细胞系U937的粘附敏感，表明该hiPSC-ECs衍生微系统可模拟内皮细胞在生理和病理过程中的炎症反应。
Endothelial cells (ECs) have great potential in vascular diseases research and regenerative medicine. Autologous human ECs are difficult to acquire in sufficient numbers in vitro, and human induced pluripotent stem cells (iPSCs) offer unique opportunity to generate ECs for these purposes. In this work, we present a new and efficient method to simply differentiate human iPSCs into functional ECs, which can respond to physiological level of flow and inflammatory stimulation on a fabricated microdevice. The endothelial-like cells were differentiated from human iPSCs within only one week, according to the inducing development principle. The expression of endothelial progenitor and endothelial marker genes (GATA2, RUNX1, CD34, and CD31) increased on the second and fourth days after the initial inducing process. The differentiated ECs exhibited strong expression of cells-specific markers (CD31 and von Willebrand factor antibody), similar to that present in human umbilical vein endothelial cells. In addition, the hiPSC derived ECs were able to form tubular structure and respond to vascular-like flow generated on a microdevice. Furthermore, the human induced pluripotent stem cell-endothelial cells (hiPSC-ECs) pretreated with tumor necrosis factor (TNF-α) were susceptible to adhesion to human monocyte line U937 under flow condition, indicating the feasibility of this hiPSCs derived microsystem for mimicking the inflammatory response of endothelial cells under physiological and pathological process.