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

International Journal of Molecular Sciences, vol. 22, pp. 8234

Abstract

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.

Authors 11

1. Luuk de Haan Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands

2. Johnny Suijker Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands

3. Ruthger van Roey Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands

4. Nina Berges

   Merck Healthcare KGaA, Darmstadt (Germany)

   Affiliation as printed

   Merck Healthcare KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany

5. Elissaveta P. Petrova

   Merck Healthcare KGaA, Darmstadt (Germany)

   Affiliation as printed

   Merck Healthcare KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany

6. Karla C. S. Queiroz Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands

7. Wouter Strijker Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands

8. Thomas Olivier Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands

9. Oliver Poeschke

   Merck Healthcare KGaA, Darmstadt (Germany)

   Affiliation as printed

   Merck Healthcare KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany

10. Sakshi Garg

    Merck Healthcare KGaA, Darmstadt (Germany)

    Affiliation as printed

    Merck Healthcare KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany

11. Lenie J. van den Broek corresponding Aachen Mimetas BV

    Mimetas (Netherlands)

    Affiliation as printed

    Mimetas BV, de Limes 7, 2342 DH Oegstgeest, The Netherlands