Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress
Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress
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DOI：
10.1152/japplphysiol.00232.2003
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发表时间：
2003-11-01
影响因子：
3.3
通讯作者：
Ando, J
中科院分区：
文献类型：
--
作者：
Yamamoto, K;Takahashi, T;Ando, J
内皮祖细胞(EPC)在外周血中循环，向靶组织迁移、分化并促进新血管的形成。在本研究中，我们报道了血流或组织液流动产生的剪应力可以加速内皮祖细胞的增殖、分化和毛细血管样管的形成。体外培养的人外周血内皮祖细胞在层流切应力作用下，细胞拉长，其长轴朝向流动方向。与静置培养的内皮细胞相比，剪切力作用下的内皮细胞密度更高，处于细胞周期G(2)-M期的细胞比例更大。切应力显著增加两种血管内皮生长因子受体的EPC在蛋白和mRNA水平上的表达，这两种受体分别是含有激酶插入结构域的受体和FMS样酪氨酸激酶-1，以及细胞间黏附分子血管内皮-钙粘附素。胶原凝胶中管形成的分析表明，剪切应力下的内皮祖细胞形成管状结构并形成广泛的管状网络的速度明显快于静态对照组。这些发现提示内皮祖细胞对剪切力很敏感，其血管生成活动可能受剪切力的调节。
Endothelial progenitor cells (EPCs), circulating in peripheral blood, migrate toward target tissue, differentiate, and contribute to the formation of new vessels. In this study, we report that shear stress generated by blood flow or tissue fluid flow can accelerate the proliferation, differentiation, and capillary-like tube formation of EPCs. When EPCs cultured from human peripheral blood were subjected to laminar shear stress, the cells elongated and oriented their long axes in the direction of flow. The cell density of the EPCs exposed to shear stress was higher, and a larger percentage of these cells were in the G(2)-M phase of the cell cycle, compared with EPCs cultured under static conditions. Shear stress markedly increased the EPC expression of two vascular endothelial growth factor receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase-1, and an intercellular adhesion molecule, vascular endothelial-cadherin, at both the protein and mRNA levels. Assays for tube formation in the collagen gels showed that the shear-stressed EPCs formed tubelike structures and developed an extensive tubular network significantly faster than the static controls. These findings suggest that EPCs are sensitive to shear stress and that their vasculogenic activities may be modulated by shear stress.