Lymphatic Vessel on a Chip with Capability for Exposure to Cyclic Fluidic Flow

The lymphatic system is a complex organ system that is essential in regulating the development of host immune responses. Because of the complexity of the lymphatic system and the existence of few in vitro models that replicate human lymphatic vessels, there is a need for a primary cell-based lymphatic model that can provide a better understanding of the effects of flow parameters, therapeutics, and other stimuli on lymphatic vessel behavior. In this report, a fluidic device models the cyclical lymphatic flow under normal and disease conditions. The device utilizes a pumpless design, operating with gravitational forces to simulate normal conditions with a shear of 0.092 Pa (0.92 dyn/cm(2)) as well as disease conditions with an increased shear of (0.67 Pa, 6.7 dyn/cm(2)). The cyclical pumping present in lymphatic vessels is replicated by applying shear stress for a period of 10 s multiple times per minute. Primary human lymphatic endothelial cells (HLECs) cultured in the device for 10 days produce less interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) per cell than cells cultured under static conditions. The results are consistent with previously published in vivo measurements, indicating that the fluidic device mimics conditions for IL-8 and TNF-alpha expression well. Data obtained with the devices also indicate that primary HLECs proliferate faster under high-shear than under low-shear conditions.