Engineering more physiologic in vitro models for the study of vascular biology

Recent advances in our understanding of vascular biology have been achieved using both in vivo and in vitro approaches. In vivo studies incorporate the complexity of the physiologic system yet are difficult to control, while in vitro studies can be carefully controlled but lack the totality of the environment that influences cell behavior. A promising new strategy to converge these approaches is the use of tissue engineering to create more physiologic in vitro models, which are controlled and yet also mimic the complex in vivo environment. The studies presented here focus on the responses of vascular endothelial cells at the molecular level to complex substrates and to fluid shear stress by using transcriptional profiling. The first goal was to examine the influence of substrate on gene expression under static conditions of cells on small intestinal submucosa or tissue engineered blood vessel wall model, as compared to cells on collagen I adsorbed to glass. The second goal was to examine the combined influence of substrate and mechanical environment on cell behavior by comparing endothelial cells on the tissue engineered blood vessel wall model to cells on adsorbed collagen under shear stress conditions. Results show a significant differential regulation of numerous genes including prominent trends in genes related to extracellular matrix and cell cycle. We conclude that endothelial cells are not only extensively influenced by type of extracellular matrix, presence of smooth muscle cells and application of shear stress, but also by the combined presence of these stimuli. The studies presented here are only a beginning, yet demonstrate the importance of using more complex models in vitro and the need for engineering more physiologic in vitro models for the study of vascular biology.