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Article

A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease

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Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands
2
Merck Healthcare KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Sergio Dias
Int. J. Mol. Sci. 2021, 22(15), 8234; https://doi.org/10.3390/ijms22158234
Received: 2 July 2021 / Revised: 22 July 2021 / Accepted: 26 July 2021 / Published: 30 July 2021
(This article belongs to the Section Materials Science)
The recruitment of T cells is a crucial component in the inflammatory cascade of the body. The process involves the transport of T cells through the vascular system and their stable arrest to vessel walls at the site of inflammation, followed by extravasation and subsequent infiltration into tissue. Here, we describe an assay to study 3D T cell dynamics under flow in real time using a high-throughput, artificial membrane-free microfluidic platform that allows unimpeded extravasation of T cells. We show that primary human T cells adhere to endothelial vessel walls upon perfusion of microvessels and can be stimulated to undergo transendothelial migration (TEM) by TNFα-mediated vascular inflammation and the presence of CXCL12 gradients or ECM-embedded melanoma cells. Notably, migratory behavior was found to differ depending on T cell activation states. The assay is unique in its comprehensiveness for modelling T cell trafficking, arrest, extravasation and migration, all in one system, combined with its throughput, quality of imaging and ease of use. We envision routine use of this assay to study immunological processes and expect it to spur research in the fields of immunological disorders, immuno-oncology and the development of novel immunotherapeutics. View Full-Text
Keywords: T cell; microfluidic; high-throughput; transendothelial migration; extravasation; inflammation; immuno-oncology; in vitro; organ-on-a-chip T cell; microfluidic; high-throughput; transendothelial migration; extravasation; inflammation; immuno-oncology; in vitro; organ-on-a-chip
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MDPI and ACS Style

de Haan, L.; Suijker, J.; van Roey, R.; Berges, N.; Petrova, E.; Queiroz, K.; Strijker, W.; Olivier, T.; Poeschke, O.; Garg, S.; van den Broek, L.J. A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease. Int. J. Mol. Sci. 2021, 22, 8234. https://doi.org/10.3390/ijms22158234

AMA Style

de Haan L, Suijker J, van Roey R, Berges N, Petrova E, Queiroz K, Strijker W, Olivier T, Poeschke O, Garg S, van den Broek LJ. A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease. International Journal of Molecular Sciences. 2021; 22(15):8234. https://doi.org/10.3390/ijms22158234

Chicago/Turabian Style

de Haan, Luuk, Johnny Suijker, Ruthger van Roey, Nina Berges, Elissaveta Petrova, Karla Queiroz, Wouter Strijker, Thomas Olivier, Oliver Poeschke, Sakshi Garg, and Lenie J. van den Broek. 2021. "A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease" International Journal of Molecular Sciences 22, no. 15: 8234. https://doi.org/10.3390/ijms22158234

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