A versatile microfluidic platform for the study of cellular interactions between endothelial cells and neutrophils

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 5; pp. 1122 - 1130
• Main Authors: Wu, Xiaojie, Newbold, Molly A., Gao, Zhe, Haynes, Christy L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2017
• Subjects: Angiogenesis; cardiovascular diseases; Cell Communication - physiology; cell movement; Cell Movement - physiology; Cells, Cultured; Chemokine; chemokines; Chemokines - metabolism; drugs; endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - physiology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiology; gels; growth and development; Humans; immune response; in vitro studies; Microfluidic; Microfluidics - methods; Migration; neoplasms; Neutrophil; Neutrophil Infiltration - physiology; neutrophils; Neutrophils - metabolism; Neutrophils - physiology; pathogenesis; Receptor expression; Vascular Endothelial Growth Factor A - metabolism; vascular endothelial growth factors; Chemokine; Angiogenesis; Neutrophil; Migration; Receptor expression; Microfluidic
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.02.012

Endothelial migration is a critical physiological process during vascular angiogenesis, growth and development, as well as in various disease conditions, such as cancer and cardiovascular diseases. Neutrophil migration, known as the important characteristic of immune responses, is also recognized as a contributor to the diseases involving endothelial migration. Herein, the mutually dependent relationship between neutrophil recruitment and endothelial migration was studied on a microfluidic platform for the first time. An in vivo-like microenvironment is created inside microfluidic devices by embedding a gel scaffold into the micro-chambers. This approach, with controllable stable chemical gradients and the ability to quantitate interaction characteristics, overcomes the limitations of the current in vivo and in vitro assays for cell migration studies. The number of neutrophils migrating through the endothelial cell layer is heavily influenced by the concentration of vascular endothelial growth factor (VEGF) that induces endothelial cell migration in the gel scaffold, and is not as correlated to the concentration of chemokine solution used for initiating neutrophil migration. More importantly, neutrophil migration diminishes the effects of the drug that inhibits endothelial migration and this process is regulated by the concentration of chemokine molecules instead of VEGF concentration. The results presented herein demonstrate the complicated cellular interactions between endothelial cells and neutrophils: endothelial migration delicately regulates neutrophil migration while the presence of neutrophils stabilizes the structures of endothelial migration. This study provides deeper understanding of the dynamic cellular interactions between neutrophils and endothelial cells as well as the pathogenesis of relevant diseases. •Multi-component microfluidics recapitulate the neutrophil/endothelial cell interaction microenvironment.•Endothelial cells delicately regulate neutrophil migration.•Neutrophils are critical for stabilizing endothelial structures.