The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip

Abstract

Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these approaches fail to fully reflect the multifactorial and complex in vivo environment (e.g., including microbiota, nutrition, and immune response) in the gut system. Although conventional models such as cell lines, Ussing chamber, and the everted sac are still used, increasingly more sophisticated intestinal models have been developed over the past years including organoids, InTESTine™ and microfluidic gut-on-chip. In this review, we gathered the most recent insights on the setup, advantages, limitations, and future perspectives of most frequently used in vitro and ex vivo models to study intestinal physiology and functions in health and disease.

In Vitro Methods for Measuring the Permeability of Cell Monolayers

“…This experimental technique was applied in a wide array of research areas, including the study on the mechanisms of diarrheal disease in the setting of Salmonella infection and on the regulation of epithelial chloride secretion by the epidermal growth factor receptor [33], and the research on the cytotoxic effect of smoke from polymer combustion on human lungs [32]. For a long time, the Using chamber systems have been the most frequently used for the study of intestinal epithelium [34], but more recent papers describe the research on the airway epithelia, including the targeting of prostaglandin receptors in cystic fibrosis (CF) treatment [35].…”

A Planar Culture Model of Human Absorptive Enterocytes Reveals Metformin Increases Fatty Acid Oxidation and Export

“…Traditionally, cell culture models of human SI epithelium largely have relied on cancer or transimmortalized mouse intestinal cell lines (ie, Caco-2, 16 m-ICcl2, 17 and so forth), which retain properties consistent with undifferentiated states. [18][19][20] Organoid culture models have become popular alternatives because they typically are derived from primary intestinal epithelial stem cells (ISCs) and can differentiate into the main mature lineages of the differentiated gut epithelium. 21,22 Organoids are small (diameter, w100-1000 mm) spherical structures cultured in thick hydrogels.…”

Pro-Inflammatory Cytokines Trigger the Overexpression of Tumour-Related Splice Variant RAC1B in Polarized Colorectal Cells

“…The resulting transepithelial barrier is a characteristic of colon mucosa and better resembles the early events in colon tumorigenesis than conventional monolayer formation on plastic dishes. In this work, both colorectal cell lines were grown on microporous membranes and reached a TEER of up to 600 Ω•cm 2 after 12-14 days (Figures 1 and 7), a period during which they seal the lateral intercellular spaces through tight junction formation [37,49] and functionally separate the apical and basolateral plasma membranes [50][51][52][53][54]. This is an important characteristic of our study.…”