Browsing by Author "Soleimani, Shirin"

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    Long-term co-culture of endothelial and cancer cells within biomimetic microfluidic chips for investigating juxtacrine and paracrine regulatory signaling pathways
    (2019-01) Soleimani, Shirin; Sanati-Nezhad, Amir; Rancourt, Derrick E.; Ungrin, Mark D.
    Emerging evidence on how angiocrine factors confer inductive signals to orchestrate a wide range of pathophysiological phenomena (e.g. tumorigenesis, self-renewal of hematopoietic stem cells, regenerative lung alveolization and liver regeneration) lends credence to the concept that endothelial cells are not only the building blocks of vascular networks but also serve as a rich resource of regulatory angiocrine factors. Cancer-associated endothelial cells initiate a series of signaling modes with cancer cells. These signallings determine cancer progression and response to drugs. While it is widely-believed that endothelial cells are only able to affect the cancer cells that are juxtaposed next to them, cells positioned five-cell diameters away from the sinusoid vessels have been shown to be ruled by angiocrine factors. Considering the distance dependency of cancer-endothelium crosstalk, there is a great demand for an in vitro system with high geometrical precision that offers a diverse range of cell-cell distance and cell-cell contact area for studying and distinguishing juxtacrine and paracrine signallings between cancer and endothelial cells in a spatiotemporal manner. In the present study, a three-layer microfluidic chip consisting of a top and a bottom channel separated via a porous membrane is devised, to enable studying the signalling pathways between cancer and endothelial cells under highly-controlled conditions. The porous membranes are variable in terms of pore size, thickness and porous surface area. However, transition from macroscopic to microfluidic platforms for reconstructing in vitro models brings with it a variety of challenges such as the effect of device material (Tissue culture Polystyrene vs. PDMS), surface coating, cell number/surface area unit, cell seeding method and cell culture media exchange schedule. The present work has tried to provide a comprehensive protocol to supply precisely controlled conditions along the microchannels for the cells to grow, using human umbilical vein endothelial cells, E4OR1 transduced endothelial cells and breast cancer MCF-7 cells.