Immunocompetent Human Intestinal Models in Preclinical Drug Development.

Area of Science:

• Gastroenterology
• Immunology
• Biomedical Engineering

Background:

• The intestinal epithelial barrier, microbiome, and immune system maintain gut homeostasis.
• Dysfunction of this barrier is linked to chronic inflammation, such as in inflammatory bowel diseases (IBD).
• Traditional animal models have limitations in human biological relevance for IBD preclinical research.

Purpose of the Study:

• To highlight the advantages and limitations of 2D and 3D intestinal models.
• To discuss the application of these models in studying inflammatory and immune responses in the gut.
• To emphasize their role in improving preclinical drug development for intestinal inflammatory diseases.

Main Methods:

• Review of two-dimensional (2D) and three-dimensional (3D) intestinal models.
• Comparison of coculture systems, organoids, and microfluidic devices.
• Analysis of their utility in mimicking gut physiology and pathophysiology.

Main Results:

• 3D reconstructed intestinal epithelium models, incorporating immune and microbial cells, more accurately mimic in vivo gut physiology and inflammation.
• These advanced models offer improved representation of pathophysiological changes compared to traditional methods.
• Current cell culture models still have limitations in cellular and molecular complexity.

Conclusions:

• Advanced 3D intestinal models offer enhanced biological relevance for studying IBD.
• These models are valuable tools for improving preclinical drug development in intestinal inflammatory diseases.
• Further development is needed to fully replicate in vivo complexity.