Endothelial progenitor cells promote directional three-dimensional endothelial network formation by secreting vascular endothelial growth factor.
Endothelial progenitor cells promote directional three-dimensional endothelial network formation by secreting vascular endothelial growth factor.
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DOI：
10.1371/journal.pone.0082085
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tanishita K
中科院分区：
文献类型：
--
作者：
Abe Y;Ozaki Y;Kasuya J;Yamamoto K;Ando J;Sudo R;Ikeda M;Tanishita K
内皮祖细胞（EPC）移植可诱导新生血管网络的形成，提供营养和氧气，是治疗缺血和心血管疾病的可行方法。然而，EPCs作为促血管生成细胞因子的来源和随后的细胞外生长因子微环境在三维（3D）微血管形成中的产生者的作用尚未完全了解。我们专注于使用体外3D网络模型的3D微血管形成的促血管生成细胞因子的来源的EPCs的贡献。为了建立三维网络模型，从大鼠骨髓中分离的EPCs与双层胶原凝胶夹在一起。然后在上胶原凝胶层的顶部培养内皮细胞（EC）。EC网络形成的定量分析表明，EC网络的长度，数量和深度显着增强EC和EPC的三维模型相比，EC单作。此外，条件培养基（CM）的3D模型与EC和EPC促进网络形成相比，CM从EC单一培养。我们还证实了EPCs分泌血管内皮生长因子（VEGF）。然而，用CM培养的网络是浅的，并且不能很深地穿透胶原凝胶。因此，我们得出结论，内皮祖细胞有助于三维网络的形成，至少通过间接纳入产生局部VEGF梯度。这些结果表明，在组织工程领域中，EPC的位置对于控制定向3D网络形成是重要的。
Endothelial progenitor cell (EPC) transplantation induces the formation of new blood-vessel networks to supply nutrients and oxygen, and is feasible for the treatment of ischemia and cardiovascular diseases. However, the role of EPCs as a source of proangiogenic cytokines and consequent generators of an extracellular growth factor microenvironment in three-dimensional (3D) microvessel formation is not fully understood. We focused on the contribution of EPCs as a source of proangiogenic cytokines on 3D microvessel formation using an in vitro 3D network model. To create a 3D network model, EPCs isolated from rat bone marrow were sandwiched with double layers of collagen gel. Endothelial cells (ECs) were then cultured on top of the upper collagen gel layer. Quantitative analyses of EC network formation revealed that the length, number, and depth of the EC networks were significantly enhanced in a 3D model with ECs and EPCs compared to an EC monoculture. In addition, conditioned medium (CM) from the 3D model with ECs and EPCs promoted network formation compared to CM from an EC monoculture. We also confirmed that EPCs secreted vascular endothelial growth factor (VEGF). However, networks cultured with the CM were shallow and did not penetrate the collagen gel in great depth. Therefore, we conclude that EPCs contribute to 3D network formation at least through indirect incorporation by generating a local VEGF gradient. These results suggest that the location of EPCs is important for controlling directional 3D network formation in the field of tissue engineering.
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