ADHESION AND DIFFERENTIATION OF ENDOTHELIAL-CELLS BY EXPOSURE TO CHRONIC SHEAR-STRESS - A VASCULAR GRAFT MODEL
ADHESION AND DIFFERENTIATION OF ENDOTHELIAL-CELLS BY EXPOSURE TO CHRONIC SHEAR-STRESS - A VASCULAR GRAFT MODEL
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DOI：
10.1159/000170195
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发表时间：
1995-05-01
影响因子：
3
通讯作者：
OTT, MJ
中科院分区：
文献类型：
--
作者：
BALLERMANN, BJ;OTT, MJ
由于新生内膜增生和相关的移植物血栓形成，用于血液透析通路和小口径动脉搭桥或间置的人工血管移植物的长期通畅性受到限制。考虑到内皮细胞的抗凝和血管扩张特性，如果在移植前种植一层贴壁的分化内皮细胞，这些问题可以部分解决。体内的内皮细胞具有高度的粘附性，可以抵抗血液动力学切应力的破坏，其水平远远超过生理条件。体内的内皮细胞也是高度分化的，具有有组织的细胞骨架、webel-Palade小体和带有局灶性粘连斑块的基底应力纤维。在细胞培养中，内皮细胞迅速失去了许多分化的特征，而人工表面的内皮细胞，如血管移植材料，不能足够的黏附或分化来抵抗生理剪应力。我们发现，在体外暴露于慢性剪切力的内皮细胞，经过几天的分步作用，被诱导成与基质紧密附着并显示出更多的分化特征。因此，种植于血管移植物上的血管内皮细胞在体外以阶梯切应力进行预适应，可用于改善内皮细胞的保留和分化，以便随后在体内使用。
Long-term patency of artificial vascular grafts for hemodialysis access and for bypass or interposition in small caliber arteries is limited due to neointimal hyperplasia and associated graft thrombosis. Given the anticoagulant and vasodilatory properties of endothelial cells, these problems could be partially overcome if grafts were seeded with an adherent monolayer of differentiated endothelial cells, prior to implantation. Endothelial cells in vivo are highly adherent and can resist disruption by hemodynamic shear stress at levels that far exceed physiological conditions. Endothelial cells in vivo also are highly differentiated, with an organized cytoskeleton, Weibel-Palade bodies, and basal stress fibers with focal adhesion plaques. In cell culture, endothelial cells rapidly lose many of their differentiated features, and endothelial cells on artificial surfaces, like vascular graft material, are not sufficiently adherent or differentiated to resist physiologic shear stress. We find that endothelial cells exposed to chronic shear stress in vitro, applied in a stepwise fashion over several days, are induced to become tightly adherent to the substratum and exhibit more differentiated features. Thus, pre-conditioning of endothelial cells seeded on vascular grafts with stepwise shear stress in vitro could be used to improve endothelial cell retention and differentiation for subsequent in vivo use.