Intestinal Barrier Function
Integrity of the intestinal epithelium is crucial for the normal functioning of the lower GI tract. RepliGut maintains barrier integrity with high TEER values. Compounds can be assessed for the potential to disrupt barrier function or the barrier can be compromised with cytokines and the reestablishment of barrier function quantified.
Inflammation of the GI tract is the main hallmark of Inflammatory Bowel Disease. The RepliGut system is comprised of polarized intestinal cells grown on transwells. Dosing with compounds can be in the luminal or basolateral compartments and sampling for the release of inflammatory mediators can be quantified in either compartment as well.
GI toxicities are among the most common adverse events during Phase 1 clinical trials. RepliGut recapitulates intestinal epithelium and can be used to screen compounds for drug-induced GI toxicity early in the drug development process.
Intestinal Drug Disposition
RepliGut can be used to measure the uptake or efflux of compounds in a manner similar to Caco-2 cells. RepliGut is superior to Caco-2 cells because the cells are not transformed and studies can be conducted with cells derived from the different regions of the small intestine and colon. More than one donor can be tested.
Available biological endpoints
- Transepithelial electrical resistance (TEER)
- Permeability (Papp or % of control)
- mRNA Expression (RT-PCR)
- Cytotoxicity (ATP levels, membrane leakiness)
- Protein Expression (ELISA)
- High Content Imaging