Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes.
Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes.
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DOI：
10.1371/journal.pone.0084179
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Uzan G
中科院分区：
文献类型：
--
作者：
Boyer-Di Ponio J;El-Ayoubi F;Glacial F;Ganeshamoorthy K;Driancourt C;Godet M;Perrière N;Guillevic O;Couraud PO;Uzan G
血管系统适应于不同组织和器官中的特定功能。血管内皮细胞是这种适应的重要因素，导致了“特化内皮细胞”的概念。这些细胞的表型高度依赖于其特定的微环境，并且当分离和培养时，它们在几次传代后失去其特定特征，使得使用此类细胞的模型预测性差且不可重现。我们提出了一种新的来源，专门的内皮细胞的基础上脐带血循环内皮祖细胞（EPCs）。作为原型的例子，我们评估了EPCs在特定诱导培养条件下获得脑微血管内皮细胞（血脑屏障（BBB））或动脉内皮细胞特性的能力。首先，我们证明了EPC衍生的内皮细胞（EPDCs）与星形胶质细胞共培养获得了几个BBB表型特征，如限制亲水性溶质的细胞旁扩散和紧密连接蛋白的表达。第二，我们观察到在高浓度VEGF中培养相同的EPDCs，通过激活Notch信号传导，导致大多数动脉内皮标志物的表达增加。因此，我们已经证明，在特定条件下体外培养早期传代人脐带血EPDCs可以诱导血脑屏障或动脉表型的表型变化，表明这些EPDCs保持足够的可塑性，以获得各种专门的表型的特征。我们建议，EPDCs的这种特性可能会被利用，用于生产专门的内皮细胞培养用于药物测试和预测体外试验。
The vascular system is adapted to specific functions in different tissues and organs. Vascular endothelial cells are important elements of this adaptation, leading to the concept of ‘specialized endothelial cells’. The phenotype of these cells is highly dependent on their specific microenvironment and when isolated and cultured, they lose their specific features after few passages, making models using such cells poorly predictive and irreproducible. We propose a new source of specialized endothelial cells based on cord blood circulating endothelial progenitors (EPCs). As prototype examples, we evaluated the capacity of EPCs to acquire properties characteristic of cerebral microvascular endothelial cells (blood-brain barrier (BBB)) or of arterial endothelial cells, in specific inducing culture conditions. First, we demonstrated that EPC-derived endothelial cells (EPDCs) co-cultured with astrocytes acquired several BBB phenotypic characteristics, such as restricted paracellular diffusion of hydrophilic solutes and the expression of tight junction proteins. Second, we observed that culture of the same EPDCs in a high concentration of VEGF resulted, through activation of Notch signaling, in an increase of expression of most arterial endothelial markers. We have thus demonstrated that in vitro culture of early passage human cord blood EPDCs under specific conditions can induce phenotypic changes towards BBB or arterial phenotypes, indicating that these EPDCs maintain enough plasticity to acquire characteristics of a variety of specialized phenotypes. We propose that this property of EPDCs might be exploited for producing specialized endothelial cells in culture to be used for drug testing and predictive in vitro assays.
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影响因子：
5.3
作者：
Fujii, Takaaki;Yonemitsu, Yoshikazu;Sueishi, Katsuo
通讯作者：
Sueishi, Katsuo
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR
Wnt/β-catenin信号传导控制血脑屏障的发展。
影响因子：
7.8
作者：
Liebner, Stefan;Corada, Monica;Bangsow, Thorsten;Babbage, Jane;Taddei, Andrea;Czupalla, Cathrin J.;Reis, Marco;Felici, Angelina;Wolburg, Hartwig;Fruttiger, Marcus;Taketo, Makoto M.;von Melchner, Harald;Plate, Karl Heinz;Gerhardt, Holger;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta
影响因子：
4.6
作者：
le Noble, F;Moyon, D;Eichmann, A
通讯作者：
Eichmann, A
DOI：
10.1161/atvbaha.111.228999
发表时间：
2011-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Atkins GB;Jain MK;Hamik A
通讯作者：
Hamik A