An Immune Microenvironment-Integrated Intestinal-on-a-Chip Model for Investigating Immunopathogenesis in Inflammatory...

Area of Science:

• Biomedical Engineering
• Gastroenterology
• Immunology

Background:

• Inflammatory bowel disease (IBD) pathogenesis is complex and not fully understood.
• Traditional 2D cell culture models fail to replicate the intricate in vivo microenvironment crucial for IBD research.

Purpose of the Study:

• To develop an advanced intestinal-on-a-chip model that integrates immune components to better simulate IBD.
• To investigate the mechanisms of intestinal barrier dysfunction in IBD using this novel model.

Main Methods:

• Engineered a microfluidic chip for co-culturing intestinal epithelial (Caco-2) cells and macrophages.
• Simulated IBD pathological conditions through inflammatory stimulation.
• Utilized Infliximab as a model drug to assess therapeutic intervention.

Main Results:

• Inflammatory stimulation induced macrophage polarization (M0 to M1) and increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β).
• This inflammatory response disrupted tight junction proteins (e.g., ZO-1) in Caco-2 cells, compromising epithelial barrier integrity.
• Infliximab treatment successfully inhibited TNF-α, modulated macrophage polarization, and restored epithelial barrier function.

Conclusions:

• The developed intestinal-on-a-chip model accurately recapitulates key macrophage-epithelial interactions in IBD.
• This platform offers a robust tool for studying intestinal barrier dysfunction mechanisms.
• It serves as a valuable system for developing and testing targeted IBD therapies.