Scientific notes

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

Introduction

Microfluidic 3D Endothelium-on-a-Chip – The endothelium is a thin membrane that lines the heart and blood vessels. Endothelial cells secrete chemicals that regulate vascular relaxation and contraction, as well as enzymes that regulate blood clotting, immunological function, and platelet adhesion (a whitish material found in the blood).

Endothelial dysfunction has been found to be important in predicting stroke and heart attacks due to the arteries’ failure to expand completely. Excessive blood pressure, diabetes, high cholesterol, and smoking may all contribute to the malfunction.

3d-cell-culture-Microfluidic-3D-Endothelium-on-a-Chip

Find out in this article below how the authors use a Microfluidic 3D Endothelium-on-a-Chip to Study Transendothelial Migration and what future it holds for Organ-on-a-chip.

How to culture vascularized & immunocompetent 3D models in a standard Multiwell

Abstract

The author states that “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 underflow 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 modeling 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.

References

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. Int J Mol Sci. 2021 Jul 30;22(15):8234. doi: 10.3390/ijms22158234. PMID: 34361000; PMCID: PMC8347346.

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