Human cell-based 3D tissue constructs play an increasing role in disease modeling and drug screening. Inflammation, atherosclerosis, and many autoimmune disorders involve the interactions between immune cells and blood vessels. However, it has been difficult to image and model these interactions under realistic conditions. In this study, we fabricated a perfusion and imaging chamber to allow the real-time visualization of leukocyte perfusion, adhesion, and migration inside a tissue-engineered blood vessel (TEBV). We monitored the elevated monocyte adhesion to the TEBV wall and transendothelial migration (TEM) as the TEBV endothelium was activated by the inflammatory cytokine TNF-α. We demonstrated that treatment with anti-TNF-α or an NF-kB signaling pathway inhibitor would attenuate the endothelium activation and reduce the number of leukocyte adhesion (>74%) and TEM events (>87%) close to the control. As the first demonstration of real-time imaging of dynamic cellular events within a TEBV, this work paves the way for drug screening and disease modeling in TEBV-associated microphysiological systems.

中文翻译：

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实时观察组织工程血管中白细胞与内皮的相互作用†

基于人类细胞的3D组织构造在疾病建模和药物筛选中起着越来越重要的作用。炎症，动脉粥样硬化和许多自身免疫性疾病涉及免疫细胞和血管之间的相互作用。然而，在现实条件下很难对这些相互作用进行成像和建模。在这项研究中，我们制造了一个灌注和成像室，以实时观察组织工程血管（TEBV）中白细胞的灌注，黏附和迁移情况。当TEBV内皮被炎性细胞因子TNF-α激活时，我们监测了单核细胞粘附到TEBV壁和跨内皮迁移（TEM）的升高。我们证明，用抗TNF-α或NF-kB信号通路抑制剂进行治疗将减弱内皮细胞的活化并减少白细胞粘附的数量（> 74％）和TEM事件（> 87％），接近于对照组。作为TEBV中动态细胞事件实时成像的首次展示，这项工作为与TEBV相关的微生理系统中的药物筛选和疾病建模铺平了道路。