Exposure of Induced Pluripotent Stem Cell-Derived Vascular Endothelial and Smooth Muscle Cells in Coculture to Hemodynamics Induces Primary Vascular Cell-Like Phenotypes.
Exposure of Induced Pluripotent Stem Cell-Derived Vascular Endothelial and Smooth Muscle Cells in Coculture to Hemodynamics Induces Primary Vascular Cell-Like Phenotypes.
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DOI：
10.1002/sctm.17-0004
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发表时间：
2017-08
影响因子：
6
通讯作者：
Wamhoff BR
中科院分区：
文献类型：
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作者：
Collado MS;Cole BK;Figler RA;Lawson M;Manka D;Simmers MB;Hoang S;Serrano F;Blackman BR;Sinha S;Wamhoff BR
人诱导多能干细胞（iPSC）可以分化为血管内皮（iEC）和平滑肌（iSMC）细胞。然而，由于iEC和iSMC不是来源于完整的血管，因此它们代表不成熟的表型。血流动力学和异型细胞间通讯在血管细胞表型调控中起重要作用。在此，我们检验了iEC与iSMC共培养时血流动力学暴露诱导体内样表型的假设。iEC和iSMC在血管区域特异性血流血流动力学条件下共培养，并与血管源性内皮（PEC）和平滑肌（pSMC）细胞的血流动力学共培养物进行比较。血流动力学诱导的基因表达在佩奇和iEC以及pSMC和iSMC之间呈正相关。虽然内皮型一氧化氮合酶3蛋白在iEC中低于佩奇，但iEC功能成熟，如乙酰化低密度脂蛋白（LDL）摄取所示。SMC收缩蛋白标志物在pSMC和iSMC之间也呈正相关。iEC和佩奇暴露于含氧化LDL的动脉粥样硬化酮血流动力学诱导了两者的炎症反应。转化生长因子β（TGFβ）通路功能障碍见于多种血管疾病，iEC和iSMC在对LY 2109761介导的转化生长因子β受体I/II（TGFβRI/II）抑制的应答中分别表现出与佩奇和pSMC相似的转录组prolife。虽然与血管相比，来自iPSC的EC和SMC之间存在差异，但血液动力学共培养恢复了它们对与血管疾病相关的病理刺激的反应的高度相似性。因此，暴露于血流动力学的iPSC衍生的血管细胞可以为建模罕见血管疾病和测试新的治疗方法提供可行的系统。干细胞转化医学2017;6：1673-1683
Human induced pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC) cells. However, because iECs and iSMCs are not derived from an intact blood vessel, they represent an immature phenotype. Hemodynamics and heterotypic cell:cell communication play important roles in vascular cell phenotypic modulation. Here we tested the hypothesis that hemodynamic exposure of iECs in coculture with iSMCs induces an in vivo‐like phenotype. iECs and iSMCs were cocultured under vascular region‐specific blood flow hemodynamics, and compared to hemodynamic cocultures of blood vessel‐derived endothelial (pEC) and smooth muscle (pSMC) cells. Hemodynamic flow‐induced gene expression positively correlated between pECs and iECs as well as pSMCs and iSMCs. While endothelial nitric oxide synthase 3 protein was lower in iECs than pECs, iECs were functionally mature as seen by acetylated‐low‐density lipoprotein (LDL) uptake. SMC contractile protein markers were also positively correlated between pSMCs and iSMCs. Exposure of iECs and pECs to atheroprone hemodynamics with oxidized‐LDL induced an inflammatory response in both. Dysfunction of the transforming growth factor β (TGFβ) pathway is seen in several vascular diseases, and iECs and iSMCs exhibited a transcriptomic prolife similar to pECs and pSMCs, respectively, in their responses to LY2109761‐mediated transforming growth factor β receptor I/II (TGFβRI/II) inhibition. Although there are differences between ECs and SMCs derived from iPSCs versus blood vessels, hemodynamic coculture restores a high degree of similarity in their responses to pathological stimuli associated with vascular diseases. Thus, iPSC‐derived vascular cells exposed to hemodynamics may provide a viable system for modeling rare vascular diseases and testing new therapeutic approaches. Stem Cells Translational Medicine 2017;6:1673–1683
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影响因子：
1.2
作者：
Banerjee, Saswati;Dhara, Sujoy K.;Bacanamwo, Methode
通讯作者：
Bacanamwo, Methode
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.9
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
通讯作者：
Garcia-Cardena, Guillermo
DOI：
10.1088/1742-5468/2008/10/p10008
发表时间：
2008-10-01
影响因子：
2.4
作者：
Blondel, Vincent D.;Guillaume, Jean-Loup;Lefebvre, Etienne
通讯作者：
Lefebvre, Etienne
影响因子：
46.9
作者：
通讯作者：
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