Mucus-producing 3D cell culture models

Macedo, Maria Helena; Baião, Ana; Pinto, Soraia; Barros, Andreia S.; Almeida, Helena; Almeida, Andreia; Neves, José das

doi:10.1016/j.addr.2021.113993

Cited by 4 publications

(2 citation statements)

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“…With respect to mucus production, PAS staining and MUC2 immunostaining revealed the mucus layer in the partially laminated model. The thickness of the mucus layer can affect intestinal absorption [ 10 , 16 , 30 , 31 ]. Mucin proteins associate with lipids, which allows for hydrophobic interactions with drugs, decreasing diffusion rates in the mucus [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…The mucus layer covering the gut epithelial surface functions as a barrier to certain drugs and delivery systems, as well as microorganisms and toxins [ 10 ]. Goblet cells are the second most abundant cells in the gastrointestinal epithelium that secrete mucus to cover the mucosal surface, acting as a physical barrier based on its viscosity and mesh structure [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Caco-2 Cell Sheet Partially Laminated with HT29-MTX Cells as a Novel In Vitro Model of Gut Epithelium Drug Permeability

Cheng,

Watanabe,

Ando

et al. 2023

Pharmaceutics

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The intestinal epithelial Caco-2 cell monolayer is a well-established in vitro model useful for predicting intestinal drug absorption in humans. Coculture models of Caco-2 and goblet-cell-like HT29-MTX cells have been developed to overcome the lack of a mucus layer; however, those models are much leakier compared to the intestinal epithelium. Here, we developed a partially laminated culture model where HT29-MTX cells were superimposed onto a Caco-2 monolayer to overcome this issue. A morphological study showed that the piled HT29-MTX cells were voluntarily incorporated into the Caco-2 monolayer, and mucus production was confirmed via periodic acid-Schiff and mucin protein 2 staining. Permeability was evaluated in terms of transepithelial electrical resistance (TEER) and the apparent permeability of paracellular markers with different molecular sizes. The partially laminated model maintained the high barrier function of the Caco-2 monolayer, whose permeability appeared adjustable according to the HT29-MTX/Caco-2 cell ratio. In contrast, the coculture models showed abnormally high permeability of those markers, correlated with low TEER. Thus, the partially laminated model enabled in vitro recapitulation of effective mucosal barrier function. Consequently, this novel model may be useful as an in vitro high-throughput evaluation system for enteral mucosal permeability and mucus-penetrating efficiency of drugs and nanocarriers.

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