A platform to reproducibly evaluate human colon permeability and damage.

Area of Science:

• Gastroenterology
• Biomedical Engineering
• Cell Biology

Background:

• The intestinal epithelium forms a critical barrier against pathogens and irritants.
• Disruption of this barrier is linked to inflammatory bowel disease and sepsis.
• Existing animal models for intestinal permeability are limited in predicting human biology.

Purpose of the Study:

• To develop a high-throughput human colon organ-on-chip model for assessing epithelial barrier function.
• To create a predictive system for colon barrier damage and healing.
• To establish a model relevant to Inflammatory Bowel Disease (IBD) for therapeutic studies.

Main Methods:

• Integration of primary human colon stem cells into the PREDICT96 microfluidic organ-on-chip platform.
• Pharmacological induction of barrier damage.
• Measurement of barrier integrity using molecular permeability assays and transepithelial electrical resistance (TEER).

Main Results:

• Demonstrated pharmacologically induced barrier damage in the organ-on-chip model.
• Successfully measured barrier damage using high-throughput molecular permeability and TEER assays.
• Developed an Inflammatory Bowel Disease-relevant model using cytokine-induced damage.

Conclusions:

• The developed human colon organ-on-chip platform provides a robust, high-throughput system for studying colon epithelial barrier function.
• This model accurately predicts barrier damage and healing, offering a valuable alternative to animal models.
• The IBD-relevant model supports research into disease mechanisms and the evaluation of potential therapeutics for inflammatory bowel disease.