We are interested in lymphatic vessel physiology and how lymphatic functions are mediated by the biochemical and biophysical environment of the lymphatic endothelium. Understanding lymphatic growth and function modulation is necessary not only to develop novel therapies to restore lymphatic transport in pathologies such as lymphedema, but also to better exploit lymphatics for lymph node targeting in vaccination and immunotherapies. We developed multiple mouse models to characterize lymphatic vessel formation (lymphangiogenesis), remodeling and transport functions. To explore dynamics of cell and extracellular component interactions with lymphatics, we recently described a novel intravital imaging technique to observe the live mouse ear dermis. We also established a method to selectively deplete lymphatics, namely photodynamic therapy. In this method, a photosensitizer is injected in the mouse dermis and collected by lymphatics. Then, upon light exposure, free radicals are generated and destroy lymphatics locally. This allows to subsequently determine the consequences of lymphatic depletion, and regeneration processes.
Using novel 3D interstitial flow tissue culture models, we showed that lymphatics actively regulate tissue fluid drainage and immune cell trafficking, and that this process was dependent on transmural flow. Further studies aim to characterize the active roles of lymphatics in antigen transport and processing, and their implications in immune responses.
“Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling,” Güç E, Briquez PS, Foretay D, Fankhauser MA, Hubbell JA, Kilarski WW, Swartz MA. Biomaterials, 2017
“Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress,” Triacca V, Guc E, Kilarski WW, Pisano M, Swartz MA. Circulation Research, 2017
“Intravital immunofluorescence for visualizing the microcirculatory and immune microenvironments in the mouse ear dermis”, Kilarski WW, Güç E, Teo JC, Oliver SR, Lund AW, Swartz MA. PLoS One, 2013
“Transmural flow modulates cell and fluid transport functions of lymphatic endothelium”, Miteva DO, Rutkowski JM, Dixon JB, Kilarski W, Shields JD, and Swartz MA. Circulation Research, 2010