by Keyword: intestinal models
García-Díaz, María, Cendra, Maria del Mar, Alonso-Roman, Raquel, Urdániz, María, Torrents, Eduard, Martínez, Elena, (2022). Mimicking the Intestinal Host–Pathogen Interactions in a 3D In Vitro Model: The Role of the Mucus Layer Pharmaceutics 14, 1552
The intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time, the intestinal mucus accommodates the resident microbiota, providing nutrients and attachment sites, and therefore playing an essential role in the host–pathogen interactions and gut homeostasis. Underneath this mucus layer, the intestinal epithelium is organized into finger-like protrusions called villi and invaginations called crypts. This characteristic 3D architecture is known to influence the epithelial cell differentiation and function. However, when modelling in vitro the intestinal host–pathogen interactions, these two essential features, the intestinal mucus and the 3D topography are often not represented, thus limiting the relevance of the models. Here we present an in vitro model that mimics the small intestinal mucosa and its interactions with intestinal pathogens in a relevant manner, containing the secreted mucus layer and the epithelial barrier in a 3D villus-like hydrogel scaffold. This 3D architecture significantly enhanced the secretion of mucus. In infection with the pathogenic adherent invasive E. coli strain LF82, characteristic of Crohn’s disease, we observed that this secreted mucus promoted the adhesion of the pathogen and at the same time had a protective effect upon its invasion. This pathogenic strain was able to survive inside the epithelial cells and trigger an inflammatory response that was milder when a thick mucus layer was present. Thus, we demonstrated that our model faithfully mimics the key features of the intestinal mucosa necessary to study the interactions with intestinal pathogens.
JTD Keywords: barrier function, bile-salts, cells, drug-delivery, host-pathogen interaction, hydrogels, ileal mucosa, infection, intestinal models, intestinal mucus, microbiome, patient, responses, 3d in vitro models, Invasive escherichia-coli
Macedo, Maria Helena, Araújo, Francisca, Martínez, Elena, Barrias, Cristina, Sarmento, Bruno, (2018). iPSC-Derived enterocyte-like cells for drug absorption and metabolism studies Trends in Molecular Medicine 24, (8), 696-708
Intestinal cell models have been widely studied and used to evaluate absorption and metabolism of drugs in the small intestine, constituting valuable tools as a first approach to evaluate the behavior of new drugs. However, such cell models might not be able to fully predict the absorption mechanisms and metabolic pathways of the tested compounds. In recent years, induced pluripotent stem cells (iPSCs) differentiated into enterocyte-like cells have been proposed as more biorelevant intestinal models. In this review, we describe mechanisms underlying the differentiation of iPSCs into enterocyte-like cells, appraise the usefulness of these cells in tridimensional intestinal models, and discuss their suitability to be used in the future for drug screening.
JTD Keywords: iPSCs, Enterocytes, Differentiation, Small intestine, Drug absorption, Intestinal models