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

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Immunology

Background:

• The lymphatic system is crucial for immune response regulation.
• Limited in vitro models exist for studying human lymphatic vessels.
• A need exists for primary cell-based models to understand flow effects on lymphatic vessels.

Purpose of the Study:

• To develop and validate a fluidic device simulating cyclical lymphatic flow.
• To investigate the behavior of primary human lymphatic endothelial cells (HLECs) under varying shear stress conditions.
• To assess the impact of simulated lymphatic flow on inflammatory marker expression and cell proliferation.

Main Methods:

• A pumpless fluidic device was designed to model normal (0.092 Pa) and disease (0.67 Pa) shear stress conditions.
• Cyclical flow was simulated by applying shear stress for 10-second intervals multiple times per minute.
• Primary human lymphatic endothelial cells (HLECs) were cultured in the device for 10 days.

Main Results:

• HLECs cultured in the fluidic device produced less interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) per cell compared to static cultures.
• These findings align with in vivo measurements, validating the device's ability to mimic physiological conditions.
• Primary HLECs demonstrated faster proliferation under high-shear conditions than under low-shear conditions.

Conclusions:

• The developed fluidic device effectively models human lymphatic flow and endothelial cell responses.
• Simulated lymphatic flow influences inflammatory mediator production and cell proliferation.
• This model provides a valuable tool for studying lymphatic vessel behavior and potential therapeutic interventions.