Vascular inflammation on a chip: A scalable platform for trans-endothelial electrical resistance and immune cell migration

Haley Ehlers; Arnaud Nicolas; Frederik Schavemaker; Jeroen P M Heijmans; Martin Bulst; Sebastiaan J Trietsch; Lenie J van den Broek

doi:10.3389/fimmu.2023.1118624

Vascular inflammation on a chip: A scalable platform for trans-endothelial electrical resistance and immune cell migration

Front Immunol. 2023 Jan 24:14:1118624. doi: 10.3389/fimmu.2023.1118624. eCollection 2023.

Authors

Haley Ehlers^{1

2}, Arnaud Nicolas^{1

2}, Frederik Schavemaker¹, Jeroen P M Heijmans¹, Martin Bulst³, Sebastiaan J Trietsch¹, Lenie J van den Broek¹

Affiliations

¹ Mimetas B.V., Leiden, Netherlands.
² Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
³ Sciospec GmbH, Bennewitz, Germany.

Abstract

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.

Keywords: TEER; TNFα, INF-γ and OrganoPlate; endothelium; immune cell migration; organ-on-a-chip; vascular inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Movement
Electric Impedance
Humans
Inflammation*
Lab-On-A-Chip Devices
Leukocytes, Mononuclear*

Grants and funding

This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 813920.