Three Dimensional Microfluidic Model to Investigate Synergism of Biomechanical and Biochemical Factors on Angiogenic Sprouting
Interstitial fluid is composing more than 20 % of our body fluid, making creeping but constant flow called interstitial flow (IF) through the extracellular matrix (ECM) of tissues. Recently the roles of IF in various pathophysiology have been highlighted, such as engagement of lymphatic vessels to cancer cells and inducement of cancer cell migration toward the initial lymphatics. Previously, several microfluidic models have elucidated the effect of IF on endothelial cells, especially on angiogenic sprouting. However, an orchestration of the IF with other growth factors on sprouting angiogenesis have not yet been studied thoroughly. Here we introduce a microfluidic platform enabling observation of angiogenic sprouting under physiological condition of IF and various growth factors. Sphingosine-1 phosphate (S1P), a blood borne lipid mediator, showed significant morphological change of angiogenic sprouting together with IF. We expect that our platform would be applied to explore deeper mechanism of collaboration between biomechanical and biochemical stimuli.