Exploring Lymphatic Function: An Engineered Toolbox to Shed Light on Nature’s Invisible Vessels

Abstract

Proper lymphatic function is essential to a variety of important physiologic processes including immune cell trafficking, lipid absorption, and the regulation of fluid balance. However, the experimental difficulties associated with making actual measurements on lymphatics have slowed our understanding of these processes. In vitro experiments on isolated primary lymphatic endothelial cells or lymphatic muscle cells remove the cell from its native biological and mechanical microenvironment, making the interpretation of results challenging. In vivo experiments, on the other hand, often require highly invasive and terminal procedures to access the vessels. In this talk I will describe several experimental platforms we have developed to assist in both of these issues. By culturing cells in microenvironments that more accurately recreate their biophysical and physiologic surroundings, we seek to not only better recapitulate the in vivo state, but to explore how changes in this mechanical environment participate in the pathogenesis of lymphatic disease. Through the use of NIR imaging techniques, we can perform longitudinal studies on lymphatic function and measure lymphatic pumping pressure in a minimally invasive fashion. Finally, we have developed several approaches using a fluorescently-labeled fatty acid analogue to quantify the dynamics of lipid transport by lymphatics both in vivo and in vitro and have evidence that lymphatic transport of lipid is not the passive process that it has been historically regarded to be.