Inflammation

EpiIntestinal closely recapitulates the physiology, 3D tissue architecture, and function of the small intestine for use in pharmaceutical development applications and inflammation studies.

The Model

EpiIntestinal is a 3D reconstructed tissue model produced from normal, human cell-derived small intestine epithelial and endothelial cells and fibrobasts. The highly differentiated tissue model is produced at the air-liquid-interface (ALI) in easy-to-handle tissue culture inserts. Structural analysis of the tissue model demonstrates columnar shaped basal cells and Kerckring folds. Ultrastructurally, EpiIntestinal exhibits brush borders, functional tight junctions and mucous secreting granules, similar to in vivo tissue.

Transmission electron micrograph (TEM) of in vitro EpiIntestinal (A) and Explant tissues (B) showing Brush borders (situated at the luminal pole of the enterocyte) and tight junctions. Brush border – provides digestive and absorption surface; site for enzymes & transporters.

The Method

Effect of Inflammatory Signals on EpiIntestinal Barrier: TEER values of SMI-100-FT tissue following 96 hr. exposure to TNF-α (40 ng/ml), IFN-y (10 ng/ml), and TNF-α + IFN-y. Medium treated wells were used as untreated controls.

Cytokine release by SMI-100 tissues following exposure to inflammatory cytokines: Tissues were exposed for 24 or 48 hr to IL-1β (5 ng/ml) or TNF-α (40 ng/ml) + IFN-y (5 ng/ml) and culture supernatants were analyzed using Bio-Plex ELISA.

Cytokine release by EpiIntestinal following exposure to inflmmatory stimuli: SMI-100-FT tissues were exposed for 24 hr to IL-1β (5 ng/ml) or TNF-α (40 ng/ml) + IFN-y (5 ng/ml). Culture supernatants were analyzed using Bio-Plex ELISA.

Conclusion

The newly developed SMI tissue model will have applications in drug safety and inflammation studies. Availability of an easy-to-use, economical, and reproducible in vitro reconstructed human SMI tissue will reduce animal use, minimize the number of test compounds dropped due to permeation problems in Caco-2, and significantly improve the prediction potential for drug absorption or inflammation in humans for candidate pharmaceutical compounds.

For more information, view the EpiIntestinal Technology Page, and Technical References.