02377nas a2200289 4500000000100000000000100001008004100002260001500043653001600058653000900074653002100083653002600104653002100130653002600151100001700177700001900194700002500213700002600238700001700264700002700281700002700308245012700335856009300462490000700555520151100562022001402073 2023 d c2023-01-2410aendothelium10aTeer10aimmune migration10ainflammatory triggers10aorgan-on- a-chip10avascular inflammation1 aHaley Ehlers1 aArnaud Nicolas1 aFrederik Schavemaker1 aJeroen P. M. Heijmans1 aMartin Bulst1 aSebastiaan J. Trietsch1 aLenie J. van den Broek00aVascular inflammation on a chip: A scalable platform for trans-endothelial electrical resistance and immune cell migration uhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1118624/full0 v143 a
The vasculature system plays a critical role in inflammation processes in the body. Vascular inflammatory mechanisms are characterized by disruption of blood vessel wall permeability together with increased immune cell recruitment and migration. There is a critical need to develop models that fully recapitulate changes in vascular barrier permeability in response to inflammatory conditions. We developed a scalable platform for parallel measurements of trans epithelial electrical resistance (TEER) in 64 perfused microfluidic HUVEC tubules under inflammatory conditions. Over 250 tubules where exposed to Tumor necrosis factor alpha (TNFα) and interferon gamma (INF-γ) or human peripheral blood mononuclear cells. The inflammatory response was quantified based on changes TEER and expression of ICAM and VE-cadherin. We observed changes in barrier function in the presence of both inflammatory cytokines and human peripheral blood mononuclear cells, characterized by decreased TEER values, increase in ICAM expression as well changes in endothelial morphology. OrganoPlate 3-lane64 based HUVEC tubules provide a valuable tool for inflammatory studies in an automation compatible manner. Continuous TEER measurements enable long term, sensitive assays for barrier studies. We propose the use of our platform as a powerful tool for modelling endothelial inflammation in combination with immune cell interaction that can be used to screen targets and drugs to treat chronic vascular inflammation.
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