Multivalent biomaterial platform to control the distinct arterial venous differentiation of pluripotent stem cells.
Multivalent biomaterial platform to control the distinct arterial venous differentiation of pluripotent stem cells.
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DOI：
10.1016/j.biomaterials.2018.09.002
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发表时间：
2018-12
期刊：
影响因子：
14
通讯作者：
Dai G
中科院分区：
文献类型：
--
作者：
Dorsey TB;Kim D;Grath A;James D;Dai G
由多能干细胞分化而来的血管内皮细胞（EC）具有巨大的潜力，可用于各种治疗领域，例如血管移植的组织工程和缺血组织的血管重建。迄今为止，已经开发了各种方案来将干细胞分化为血管内皮细胞。然而，目前的方法仍然不足以驱动不同的动静脉分化。因此，迫切需要开发精细的动静脉分化方法来解决这一差距。在这里，我们开发了一个生物材料平台来模拟多价肝配蛋白-B2/EphB4信号传导，并研究其在多能干细胞早期动脉和静脉规范中的作用。我们的结果表明，水凝胶基质上固定化的 ephrinB2 或 EphB4 通过调节多种动静脉标记物对动静脉分化具有明显的影响。当与 Wnt 通路激动剂或 BMP4 信号传导相结合时，ephrin-B2/EphB4 生物材料平台可以创建不同的 EC 祖细胞群，展示各种动脉和静脉标记物以及表型标记物（如抗血栓、促动脉粥样硬化和成骨基因）的差异基因表达模式，这些标记物与动脉和静脉 EC 的体内表达模式一致。重要的是，这种独特的EC祖细胞群不能通过目前仅应用可溶性因子或血流动力学刺激的方法来实现，这说明使用生物材料平台微调发育信号提供了一种更好地控制干细胞动静脉分化的新方法。
Vascular endothelial cells (ECs) differentiated from pluripotent stem cells have enormous potential to be used in a variety of therapeutic areas such as tissue engineering of vascular grafts and re-vascularization of ischemic tissues. To date, various protocols have been developed to differentiate stem cells toward vascular ECs. However, current methods are still not sufficient to drive the distinct arterial venous differentiation. Therefore, developing refined method of arterial-venous differentiation is critically needed to address this gap. Here, we developed a biomaterial platform to mimic multivalent ephrin-B2/EphB4 signaling and investigated its role in the early arterial and venous specification of pluripotent stem cells. Our results show immobilized ephrinB2 or EphB4 on hydrogel substrates have a distinct effect on arterial venous differentiation by regulating several arterial venous markers. When in combination with Wnt pathway agonist or BMP4 signaling, the ephrin-B2/EphB4 biomaterial platform can create diverging EC progenitor populations, demonstrating differential gene expression pattern across a wide range of arterial and venous markers, as well as phenotypic markers such as anti-thrombotic, pro-atherogenic and osteogenic genes, that are consistent with the in vivo expression patterns of arterial and venous ECs. Importantly, this distinct EC progenitor population cannot be achieved by current methods of applying soluble factors or hemodynamic stimuli alone, illustrating that fine-tuning of developmental signals using the biomaterial platform offers a new approach to better control the arterial venous differentiation of stem cells.
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影响因子：
4
作者：
Bai, Hao;Gao, Yongxing;Arzigian, Melanie;Wojchowski, Don M.;Wu, Wen-shu;Wang, Zack Z.
通讯作者：
Wang, Zack Z.
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38.3
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11.8
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通讯作者：
Dejana E
影响因子：
5.2
作者：
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通讯作者：
Uzan, Georges