Development of a triculture based system for improved benefit/risk assessment in pharmacology and human food

Abstract

Caco-2 cells are widely used for both mechanistic studies in molecular cell biology as well as for studies aiming at estimating, in vitro, the bioavailability of drug candidates, xenobiotics, food compounds …. This results largely from the spontaneous differentiation of this human colon adenocarcinoma line into enterocytes-like cells in classical culture conditions, as well as from the use of bicameral culture inserts including porosity calibrated filters. Although Caco-2 cells represent the current "golden standard" of in vitro models of the human intestinal barrier, there is a trend to develop new systems mimicking more closely the intestinal epithelium for pharmaceutical and toxicological studies. In particular, goblet cells may bring a main constituent of the intestinal barrier as secreting mucus and contribute to the permeability met in vivo. In addition, gut associated M cells offer a putative way for oral delivery of nanoencapsulated therapeutic peptides and mucosal vaccines.

Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress: Mucoadhesive Chitosan vs. Poly(lactic-co-glycolic acid) Nanoparticles

“…In Figure 4c, no significant difference in TEER is observed between the dispersions tested, and, in all cases, the TEER, although decreasing in time, never drops to less than 70% of the initial value. Such a decrease is compatible with an acceptable integrity of the epithelial barrier [28] and testifies to the reliability of data represented in Figure 4a,b. These results indicate a significant promotion of permeation by PLGA NPs only with the highest concentration tested, i.e., a 2.2-fold increase in catechin (CAT) permeated over the whole time of experiment (240 min) compared to the respective control (non-encapsulated CE).…”

Organotypic and Microphysiological Human Tissue Models for Drug Discovery and Development—Current State-of-the-Art and Future Perspectives

“…Coculture moreover led to increased apical-tobasolateral permeability, which was reduced in the opposite direction, consistent with the absence of Pgp expression in HT29-MTX cells. Further extension of the model by including lymphoblast-like Raji B cells as cell models of intestinal M cells resulted in a further reduction of TEER and increased absorption of hydrophilic compounds (markers of paracellular transport) (Bazes et al, 2011;Antunes et al, 2013;Ara ujo and Sarmento, 2013;Ara ujo et al, 2016). Furthermore, the transcellular transport of nanoparticles in triple cocultures closely correlated with uptake across porcine intestinal mucosa (Schimpel et al, 2014).…”