Development of 3D Microfluidic Device to Study Endothelial-to-Mesenchymal Transformation

摘要

Our research objective is to identify the role of mechanobiology on endothelial-to-mesenchymal transformation (EndMT) by examining endothelial cell response to changes in the mechanical environment using microfluidic devices. Endothelial cells line all blood-contacting surfaces of the circulatory system and are able to sense and respond to mechanical and biochemical signals. EndMT begins when a subset of endothelial cells delaminate from the cell monolayer, lose cell-cell contacts, gain mesenchymal markers, develop an invasive and migratory phenotype, and potentially acquire mesenchymal stem cell-like properties. The transformed cells that result from EndMT are involved in embryonic tissue development, in adult tissue homeostasis such as wound healing, and in adult pathologies including fibrosis and cancer metastasis. While EndMT is well characterized in developmental biology, the mechanisms and functional role of EndMT in adult physiology have not been fully investigated. We have developed a 3D culture microfluidic bioreactor that will help us to determine the role of mechanobiology (specifically altered shear stress, altered 3D extracellular matrix composition and mechanical properties, and/or inflammatory signaling) in driving EndMT in human umbilical vein endothelial cell (HUVEC) cultures.