Design A Dynamic Flow Co-Culture System To Investigate The Effect Of Biomechanical Force Found In Vascular Niche On Cell Functions

摘要

Vascular niche plays a critical role in regulating the cellular phenotypes in cells around the niche. Because physiological parameters (e.g., flow & pressure) directly influences the functional status of vasculature, which then influence the surrounding cellular phenotypes, it is essential to study cell behaviors in a realistic, physiologically relevant system in order to better understand the interactions between the surrounding cells and the vascular niche. Here we report the design and construction of a dynamic flow co-culture system in which vascular cells and the surrounding cells can be co-cultured in the system and allowed to communicate with each other via soluble factors and cell-cell contact. The system is able to accurately replicate any pre-defined shear stress waveform and apply it to the cultured vascular cells. To validate the performance of the system, an investigation of the reaction of human umbilical vein endothelial cell (HUVEC) co-cultured with human smooth muscle cells to different shear stress environments is presented. Further investigation includes the effects of the different resulting HUVEC gene expression on cell types that are found adjacent in the vascular niche to the surrounding cells such as smooth muscle cell (SMC). A procedure was developed to provide consistent results when applying the shear force that match in vivo conditions... Overall cell morphology, alignment, growth proliferation, and RNA expression are reported of both cell lines.