Leukocyte extravasation into inflamed tissue is a complex process that is difficult to capture as a whole in vitro. We employed a bloodvessel- on-a-chip model in which human endothelial cells were cultured in a tube-like lumen in a collagen-1 matrix. The vessels are leak tight, creating a barrier for molecules and leukocytes. Addition of inflammatory cytokine TNF-α (also known as TNF) caused vasoconstriction, actin remodelling and upregulation of ICAM-1. Introducing leukocytes into the vessels allowed real-time visualization of all different steps of the leukocyte transmigration cascade, including migration into the extracellular matrix. Individual cell tracking over time distinguished striking differences in migratory behaviour between T-cells and neutrophils. Neutrophils cross the endothelial layer more efficiently than T-cells, but, upon entering the matrix, neutrophils display high speed but low persistence, whereas T-cells migrate with low speed and rather linear migration. In conclusion, 3D imaging in real time of leukocyte extravasation in a vessel-on-a-chip enables detailed qualitative and quantitative analysis of different stages of the full leukocyte extravasation process in a single assay.
|Number of pages||14|
|Journal||Journal of cell science|
|Publication status||Published - 4 Nov 2021|
Bibliographical noteFunding Information:
This work was supported by grants from the Landsteiner Foundation for Blood Transfusion Research [1649 to A.C.I.v.S.; 1820 to L.K.], the National Institutes of Health [R01AI134749, R33CA225281 and P30CA014520 to D.J.B.] and ZonMW [NWO Vici grant 91819632 to J.D.v.B.]. Deposited in PMC for release after 12 months.
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- Blood vessels
- Endothelial cells
- Extracellular matrix
- Leukocyte transendothelial migration
- Migration dynamics
- Physiological hydrogel