Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality

Area of Science:

• Gastroenterology and Bioengineering
• In vitro modeling of human physiology
• Drug discovery and development

Background:

• The intestinal mucosa is a critical barrier regulating nutrient absorption, microbial interactions, and xenobiotic metabolism.
• Accurate in vitro models are needed to study complex intestinal physiology and pathophysiology.
• Organoid and Organ-on-a-Chip technologies offer promising avenues for advanced intestinal modeling.

Purpose of the Study:

• To develop and validate human intestine-on-a-chip models for studying intestinal physiology and pathophysiology.
• To establish protocols for creating duodenum and colon chips with preserved regional characteristics.
• To demonstrate the utility of these chips for drug metabolism studies and modeling barrier disruption.

Main Methods:

• Combining organoids from human intestinal biopsies with Organ-on-a-Chip technology.
• Seeding organoids into chip compartments with co-cultured microvascular endothelial cells.
• Implementing continuous flow and peristalsis-like deformations for chip culture.
• Assessing drug metabolism (CYP3A4 induction) and modeling interferon gamma-induced barrier disruption.

Main Results:

• Successfully established human duodenum and colon chips preserving distinct cellular and molecular features.
• Demonstrated the capacity for studying drug metabolism and induction in the duodenum chip.
• Validated the modeling of interferon gamma-mediated barrier disruption, including permeability changes and cytokine secretion, in the colon chip.

Conclusions:

• Human intestine-on-a-chip models integrating organoids and microfluidics provide a powerful platform for in vitro studies.
• These models accurately recapitulate key aspects of intestinal physiology and pathophysiology.
• The developed platform facilitates drug discovery, host-microbe interaction studies, and disease modeling.