Three-tissue microphysiological system for studying inflammatory responses in gut-liver Axis.

Area of Science:

• Physiological modeling
• Microfluidics
• Immunology

Background:

• The gut-liver axis is vital for xenobiotic metabolism and disease progression.
• Axis dysfunction contributes to metabolic disorders, obesity, diabetes, and fatty liver disease.
• Immune system involvement in inflammatory responses is critical during disease progression.

Purpose of the Study:

• To develop a three-tissue microphysiological system (MPS) for modeling the gut-liver axis.
• To optimize the MPS for culturing distinct cell types (gut, immune, liver).
• To investigate inflammatory responses within this integrated system.

Main Methods:

• A microfluidic device with separated compartments for three cell types was designed.
• Computational fluid dynamics optimized channel geometry and flow conditions.
• Caco-2 (gut), RAW264.7 (immune), and HepG2 (liver) cells were cultured in the MPS.

Main Results:

• Stimulation with lipopolysaccharide (LPS) induced inflammation and nitric oxide (NO) production across connected chambers.
• The anti-inflammatory effects of luteolin were successfully demonstrated.
• The MPS effectively recapitulated gut-liver-immune cell interactions and inflammatory responses.

Conclusions:

• The developed three-tissue MPS serves as a valuable platform for studying gut-liver axis interactions.
• This model can be used to investigate disease mechanisms and evaluate therapeutic interventions.
• The MPS accurately mimics complex inflammatory processes involving multiple organs and cell types.