Department of Biohybrid & Medical Textiles (BioTex) at Center of Biohybrid Medical Systems (CBMS), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Forckenbeckstr. 55, 52074, Aachen, Germany.
Chair of Medical Materials and Implants, Department of Mechanical Engineering, School of Engineering and Design and Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstr 15, 85748, Garching, Germany.
Sci Rep. 2023 Sep 1;13(1):14384. doi: 10.1038/s41598-023-41247-6.
Endothelialization of tissue-engineered vascular grafts has proven crucial for implant functionality and thus clinical outcome, however, the choice of endothelial cells (ECs) is often driven by availability rather than by the type of vessel to be replaced. In this work we studied the response to flow of different human ECs with the aim of examining whether their response in vitro is dictated by their original in vivo conditions. Arterial, venous, and microvascular ECs were cultured under shear stress (SS) of 0, 0.3, 3, 1, 10, and 30 dyne/cm for 24 h. Regulation of flow-induced marker KLF2 was similar across the different ECs. Upregulation of anti-thrombotic markers, TM and TPA, was mainly seen at higher SS. Cell elongation and alignment was observed for the different ECs at 10 and 30 dyne/cm while at lower SS cells maintained a random orientation. Downregulation of pro-inflammatory factors SELE, IL8, and VCAM1 and up-regulation of anti-oxidant markers NQO1 and HO1 was present even at SS for which cell alignment was not observed. Our results evidenced similarities in the response to flow among the different ECs, suggesting that the maintenance of the resting state in vitro is not dictated by the SS typical of the tissue of origin and that absence of flow-induced cell orientation does not necessarily correlate with a pro-inflammatory state of the ECs. These results support the use of ECs from easily accessible sources for in vitro vascular tissue engineering independently from the target vessel.
组织工程血管移植物的内皮化已被证明对植入物的功能和临床结果至关重要，然而，内皮细胞（ECs）的选择通常取决于可用性，而不是要替代的血管类型。在这项工作中，我们研究了不同的人 ECs 对流动的反应，目的是检查它们在体外的反应是否由其原始的体内条件决定。动脉、静脉和微血管 ECs 在 0、0.3、3、1、10 和 30 达因/厘米的切应力（SS）下培养 24 小时。不同 ECs 之间的 KLF2 等流动诱导标志物的调节相似。在较高的 SS 下，主要观察到抗血栓形成标志物 TM 和 TPA 的上调。不同的 ECs 在 10 和 30 达因/厘米时观察到细胞伸长和对齐，而在较低的 SS 下，细胞保持随机取向。促炎因子 SELE、IL8 和 VCAM1 的下调和抗氧化标记物 NQO1 和 HO1 的上调即使在 SS 下也存在，而细胞对齐没有观察到。我们的结果表明，不同 ECs 对流动的反应存在相似性，这表明体外静止状态的维持不受起源组织典型的 SS 决定，并且缺乏流动诱导的细胞取向不一定与 ECs 的促炎状态相关。这些结果支持使用易于获得的 ECs 进行体外血管组织工程，而不依赖于目标血管。
