Microvasculature-on-a-chip modelling degenerative vascular disease
Blood vessels are integral to the maintenance of all tissues. They deliver oxygen and nutrients and remove waste. Blood vessels not only contain endothelial cells (ECs) that are in direct contact with flowing blood cells and fluids but they may also have pericytes (PCs) on the outside that stabilize the capillaries for example, and regulate their size, and in larger vessels, such as arterioles and venules endothelial cells they may be surrounded by vascular smooth muscle cells (vSMCs). All together they are integral for the proper functioning of the blood vessels. During inflammation, ECs in the blood capillaries become leaky and activated, so that they are more adhesive to blood cells which can result in thrombosis, increasing the chance of ischemia that causes tissue damage. The aim of this project would be to develop a 3D microvasculature-on-a-chip using human induced pluripotent stem cell (hiPSC)-derived ECs, PCs and vSMCs. Functional assays, such as vascular leakage and leukocyte recruitment would be next utilized in order to validate the system. Additional growth factor gradient formation on a chip will be examined for its effects on EC differentiation and sprouting angiogenesis. Inflammatory responses of 3D microvessels-on-chip will be determined using hPSC-derived vascular and inflammatory cells, each of which could bear vascular disease relevant mutations.