Development of a human primary gut-on-a-chip to model inflammatory processes

Area of Science:

• Gastroenterology
• Biomedical Engineering
• Cell Biology

Background:

• Inflammatory bowel disease (IBD) presents a complex challenge due to a lack of physiologically relevant in vitro models.
• Current models often balance biological relevance with scalability, limiting their utility.
• There is a critical need for advanced models to study IBD pathogenesis and therapeutic interventions.

Purpose of the Study:

• To develop an advanced gut-on-a-chip platform for modeling IBD.
• To integrate human intestinal epithelial cells (IECs) from organoids with macrophages for a multi-factorial model.
• To assess the platform's ability to replicate human intestinal physiology and inflammatory responses relevant to IBD.

Main Methods:

• Human intestinal epithelial cells (IECs) derived from organoids were cultured in a microfluidic gut-on-a-chip system.
• IECs were co-cultured with monocyte-derived macrophages to simulate the intestinal microenvironment.
• The model's response to inflammatory triggers was analyzed, including cytokine secretion and gene expression changes.

Main Results:

• Microfluidic culture enhanced IEC polarization and differentiation, closely mirroring human colon expression profiles.
• The model exhibited polarized secretion of key inflammatory cytokines (CXCL10, IL-8, CCL-20) upon activation.
• Inflammatory gene expression changes in the model correlated with known dysregulated pathways in IBD patients.
• TPCA-1 effectively inhibited inflammatory responses within the model.

Conclusions:

• The developed gut-on-a-chip platform provides a physiologically relevant in vitro model for studying IBD.
• Integration of macrophages represents a significant step towards a multi-factorial model for IBD research.
• This platform holds potential for early-stage drug development and personalized medicine approaches for IBD.