Issue 1, 2015

A novel device to concurrently assess leukocyte extravasation and interstitial migration within a defined 3D environment

Abstract

Leukocyte extravasation and interstitial migration are key events during inflammation. Traditional in vitro techniques address only specific steps of cell recruitment to tissues and fail to recapitulate the whole process in an appropriate three-dimensional (3D) microenvironment. Herein, we describe a device that enables us to qualitatively and quantitatively assess in 4D the interdependent steps underlying leukocyte trafficking in a close-to-physiology in vitro context. Real-time tracking of cells, from initial adhesion to the endothelium and subsequent diapedesis to interstitial migration towards the source of the chemoattractant within the 3D collagen matrix, is enabled by the use of optically transparent porous membranes laid over the matrix. Unique features of the device, such as the use of non-planar surfaces and the contribution of physiological flow to the establishment of a persistent chemoattractant gradient, were assessed by numerical simulations and validated by proof-of-concept, simultaneous testing of differentially treated primary mouse neutrophils. This microfluidic platform offers new and versatile tools to thoroughly investigate the stepwise process of circulating cell recruitment to target tissues in vitro and to test novel therapeutics targeting various steps of the process.

Graphical abstract: A novel device to concurrently assess leukocyte extravasation and interstitial migration within a defined 3D environment

Supplementary files

Article information

Article type
Paper
Submitted
24 Jun 2014
Accepted
26 Sep 2014
First published
29 Sep 2014

Lab Chip, 2015,15, 195-207

A novel device to concurrently assess leukocyte extravasation and interstitial migration within a defined 3D environment

R. Molteni, E. Bianchi, P. Patete, M. Fabbri, G. Baroni, G. Dubini and R. Pardi, Lab Chip, 2015, 15, 195 DOI: 10.1039/C4LC00741G

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