Linear Shear Conditioning Improves Vascular Graft Retention of Adipose-Derived Stem Cells by Upregulation of the α5β1 Integrin
Linear Shear Conditioning Improves Vascular Graft Retention of Adipose-Derived Stem Cells by Upregulation of the α5β1 Integrin
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DOI：
10.1089/ten.tea.2009.0238
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
DiMuzio, Paul J.
中科院分区：
文献类型：
--
作者：
McIlhenny, Stephen E.;Hager, Eric S.;DiMuzio, Paul J.
在血管组织工程中使用成体脂肪干细胞（ASC）作为内皮细胞替代品因其可用性而颇具吸引力。然而，当接种到脱细胞血管支架上并暴露于生理流体剪切力时，ASC 与移植管腔物理分离。在此，我们研究了使用管腔预涂层增加初始 ASC 附着的方法，以及逐渐引入剪切应力以优化 ASC 保留的新方案。与阴性对照相比，移植管腔的纤连蛋白涂层使 ASC 附着增加了近六倍。使用新型生物反应器逐渐引入接近生理的流体剪切应力，其中流速以每天 1.5 达因/厘米（2）的速率每秒增加，与传统的每日突然增加后几乎完全细胞损失相比，导致完全的管腔覆盖。暴露于剪切应力后，α(5)β(1) 整合素上调，这解释了观察到的 ASC 在移植管腔上保留的增加。这些结果表明了一种在高剪切应力微环境中将成体干细胞接种、调节和保留在脱细胞静脉支架上的新方法。
Use of adult adipose-derived stem cells (ASCs) as endothelial cell substitutes in vascular tissue engineering is attractive because of their availability. However, when seeded onto decellularized vascular scaffolding and exposed to physiological fluid shear force, ASCs are physically separated from the graft lumen. Herein we have investigated methods of increasing initial ASC attachment using luminal precoats and a novel protocol for the gradual introduction of shear stress to optimize ASC retention. Fibronectin coating of the graft lumen increased ASC attachment by nearly sixfold compared with negative controls. Gradual introduction of near physiological fluid shear stress using a novel bioreactor whereby flow rate was increased every second at a rate of 1.5 dynes/cm(2) per day resulted in complete luminal coverage compared with near complete cell loss following conventional daily abrupt increases. An upregulation of the alpha(5)beta(1) integrin was evinced following exposure to shear stress, which accounts for the observed increase in ASC retention on the graft lumen. These results indicated a novel method for seeding, conditioning, and retaining of adult stem cells on a decellularized vein scaffold within a high-shear stress microenvironment.