3D printed HUVECs/MSCs cocultures impact cellular interactions and angiogenesis depending on cell-cell distance
3D printed HUVECs/MSCs cocultures impact cellular interactions and angiogenesis depending on cell-cell distance
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DOI：
10.1016/j.biomaterials.2019.119423
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发表时间：
2019-11-01
期刊：
影响因子：
14
通讯作者：
Fisher, John
中科院分区：
文献类型：
--
作者：
Piard, Charlotte;Jeyaram, Anjana;Fisher, John
血管化是骨生长发育过程中的一个重要过程(1)，但它仍然是修复大型骨缺损的主要挑战之一。利用人脐静脉内皮细胞(HUVECs)和人间充质干细胞(HMSCs)体外共培养是目前研究最多的方法之一。这两种类型的细胞都会分泌互惠互利的特定生长因子，研究表明细胞间的交流和旁分泌可能会受到许多因素的影响。然而，关于细胞图案化和细胞群之间的距离对它们的串扰的影响，人们知之甚少。在目前的研究中，我们发现ECs和MSCs群体之间的分离和距离通过调节细胞间的通讯来影响血管生成。与MSCs相距较远的HUVECs((>；)400 PM)表现出早期血管生成(迁移/增殖)的特征。结果显示，血管内皮生长因子、成纤维细胞生长因子-2和ITGA3(整合素)表达上调，而VE-钙粘附素和血管紧张素-1表达的倍数变化较小。人脐静脉内皮细胞仍高度增殖。相反，人脐静脉内皮细胞孵育得更紧密(
Vascularization is a crucial process during the growth and development of bone (1), yet it remains one of the main challenges in the reconstruction of large bone defects. The use of in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) has been one of the most explored options. Both cell types secrete specific growth factors that are mutually beneficial, and studies suggested that cell-cell communication and paracrine secretion could be affected by a number of factors. However, little is known about the effect of cell patterning and the distance between cell populations on their crosstalk. In the present study, we showed that the separation and distance between ECs and MSCs populations affects angiogenesis by modulating cell-cell communication. HUVECs grown farther apart from MSCs ((>)400 pm) presented characteristics of an early stage of angiogenesis (migration/proliferation). Results showed an increase in the up regulation of VEGF, FGF-2, and ITGA3 (integrins) but a smaller fold change in the expression of VE-Cadherin and Ang-1. HUVECs were also still highly proliferative. On the contrary, HUVECs incubated closer (