Bioreactor application of fluid forces and influences on cell physiology for tissue engineering

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Fluid flow is a strong regulator of cell physiology, both in the body and in bioreactor systems, and modulates cardiovascular disease (CVD) progression and stem cell behavior. CVD tends to develop where blood flow changes (such as around artery curves or branches) and is typically characterized by diseased sections of blood vessels, which can rupture leading to strokes or heart attacks. Endothelial Cells (ECs) are the primary artery cells affected by fluid forces, and they perform a variety of functions that regulate blood vessel properties and health. While there is ample evidence of a role for fluid flow in CVD, relatively little is known about how ECs sense the fluid force and modify their physiology. It is difficult to isolate specific flow effects in intact vessels because conditions change rapidly with position. Similarly, stem cells offer viable options to repair diseased or damaged tissues or organs. But they often must be expanded to larger numbers in bioreactors that incorporate fluid flow. Currently employed systems contain complex hydrodynamics that do not enable identification of the effect of fluid forces on cells. Experimental systems mimicking the local environment are needed to provide a way to study what is going on inside the cells that are exposed to fluid flow. By using a customized bioreactor system to expose ECs to different flow conditions, our lab has recently discovered a new mechanism that appears to be involved in determining flow dependent outcomes. Importantly, our lab has discovered that other cell types also have the ability to use this mechanism, including stem cells. The proposed project will identify how different types of fluid flow affect activation of the new mechanism in both ECs and stem cells, and how this affects cell response to biochemicals. This information will define bioreactor schemes to enable development of novel treatments for CVD, as well as generation of stem cells. This fits into our long term goals of creating devices and technologies for cell therapy, drug discovery and testing, and medical diagnostics. These outcomes will have positive impact the health of Canadians by advancing the technology and knowledge available for disease detection, drug discovery and regenerative medicine.