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Real-time Observation of Leukocyte-Endothelium Interactions in Tissue-Engineered Blood Vessel

Abstract

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 (>25 fold) to the TEBV wall and transendothelial migration (TEM) (>70 fold) as the TEBV endothelium was activated by the inflammatory cytokine TNF-_. We demonstrated that treatment with anti-TNF-_ or an NF-kB signaling pathway inhibitor would attenuate the endothelium activation and reduce the number of leukocyte adhesion (>75%) and TEM events (>85%) 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.

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Publication details

The article was received on 23 Feb 2018, accepted on 26 May 2018 and first published on 01 Jun 2018


Article type: Paper
DOI: 10.1039/C8LC00202A
Citation: Lab Chip, 2018, Accepted Manuscript
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    Real-time Observation of Leukocyte-Endothelium Interactions in Tissue-Engineered Blood Vessel

    Z. Chen, M. Tang, D. Huang, W. Jiang, M. Li, H. Ji, J. Park, B. Xu, L. J. Atchison, G. Truskey and K. Leong, Lab Chip, 2018, Accepted Manuscript , DOI: 10.1039/C8LC00202A

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