Yamamoto Kimiko, Takahashi Tomono, Asahara Takayuki, Ohura Norihiko, Sokabe Takaaki, Kamiya Akira, Ando Joji
Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, 113-0033 Tokyo, Japan.
J Appl Physiol (1985). 2003 Nov;95(5):2081-8. doi: 10.1152/japplphysiol.00232.2003. Epub 2003 Jul 11.
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 G2-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.
内皮祖细胞（EPCs）在外周血中循环，迁移至靶组织，分化并参与新血管的形成。在本研究中，我们报告血流或组织液流动产生的剪切应力可加速EPCs的增殖、分化及类毛细血管样管腔形成。当对从人外周血中培养的EPCs施加层流剪切应力时，细胞会伸长并使其长轴沿流动方向排列。与在静态条件下培养的EPCs相比，暴露于剪切应力下的EPCs细胞密度更高，且这些细胞处于细胞周期G2-M期的比例更大。剪切应力在蛋白质和mRNA水平上均显著增加了两种血管内皮生长因子受体（含激酶插入结构域受体和fms样酪氨酸激酶-1）以及一种细胞间黏附分子（血管内皮钙黏蛋白）的EPC表达。胶原凝胶中的管腔形成试验表明，受剪切应力作用的EPCs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。这些发现表明EPCs对剪切应力敏感，且其血管生成活性可能受剪切应力调节。
