A bioreactor for in vitro studies of lymphatic endothelial cells with simultaneous fluid shear stress and membrane strain.

Reproducing the in vivo physiologic conditions and biomechanical environment to stimulate natural growth and behavior of lymphatic endothelial cells (LECs) is critical in studying the lymphatic system and its response to stimuli. In vitro studies that deconstruct the biomechanical environment, e.g.

Effect of the snake venom component crotamine on lymphatic endothelial cell responses and lymph transport.

Objective: The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life-threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.

Intracellular calcium dynamics of lymphatic endothelial and muscle cells co-cultured in a Lymphangion-Chip under pulsatile flow.

The lymphatic vascular function is regulated by pulsatile shear stresses through signaling mediated by intracellular calcium [Ca]. Further, the intracellular calcium dynamics mediates signaling between lymphatic endothelial cells (LECs) and muscle cells (LMCs), including the lymphatic tone and contractility. Although calcium signaling has been characterized on LEC monolayers under uniform or step changes in shear stress, these dynamics have not been revealed in LMCs under physiologically-relevant co-culture conditions with LECs or under pulsatile flow.

Lymphangion-chip: a microphysiological system which supports co-culture and bidirectional signaling of lymphatic endothelial and muscle cells.

The pathophysiology of several lymphatic diseases, such as lymphedema, depends on the function of lymphangions that drive lymph flow. Even though the signaling between the two main cellular components of a lymphangion, endothelial cells (LECs) and muscle cells (LMCs), is responsible for crucial lymphatic functions, there are no models that have included both cell types. Here, a fabrication technique (gravitational lumen patterning or GLP) is developed to create a lymphangion-chip.

Targeting Lymphangiogenesis and Lymph Node Metastasis in Liver Cancer.

Increased lymphangiogenesis and lymph node metastasis, the important prognostic indicators of aggressive hepatobiliary malignancies such as hepatocellular cancer and cholangiocarcinoma, are associated with poor patient outcome. The liver produces 25% to 50% of total lymphatic fluid in the body and has a dense network of lymphatic vessels. The lymphatic system plays critical roles in fluid homeostasis and inflammation and immune response.