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

Publication date: Available online 12 February 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Xiaojie Wu, Molly A. Newbold, Zhe Gao, Christy L. Haynes
BackgroundEndothelial migration is a critical physiological process during vascular angiogenesis, growth and development, as well as in multiple 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 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.MethodsAn 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 current in vivo and in vitro assays for cell migration studies.ResultsThe 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.ConclusionsThe 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 structures required for endothelial migration.General significanceThis study provides deeper understanding of the dynamic cellular interaction between neutrophils and endothelial cells as well as the pathogenesis of relevant diseases.



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