Current preclinical models offer limited predictivity when studying intestinal absorption and safety risk of orally administered drugs due to a reliance on immortalized cell lines
The Duodenum Intestine-Chip is the only commercial model of the human small intestine to incorporate pre-qualified biopsy-derived primary organoids and duodenal endothelial cells with mechanical forces to emulate in vivo physiology. The model is being applied to study duodenal physiology, drug absorption, and drug-drug interactions to improve clinical translation.
An improved model of the human duodenum
The Duodenum Intestine-Chip combines primary human duodenal organoids and small intestine microvascular endothelial cells with mechanical forces that recreate intestinal peristalsis. In this dynamic microenvironment, cells become well-polarized and exhibit in vivo-like morphology, functionality, and gene expression, while allowing for access to the apical surface.
By using primary human cells, the Duodenum Intestine-Chip more closely models human characteristics, overcoming the translational challenges of animal models caused by species differences and differences in gene expression.
Gene expression in the Duodenum Intestine-Chip more closely resembles in vivo tissue than organoids alone with significantly enriched pathways associated with metabolism, digestion, nutrient transport, and detoxification.
Major intestinal epithelial cell types—absorptive enterocytes, enteroendocrine cells, goblet cells, and Paneth cells—are present and functional on-chip in physiologically relevant ratios, with improved differentiation compared to organoids alone.
The Duodenum Intestine-Chip forms a functional intestinal barrier with well-defined epithelial tight junctions and in vivo-like permeability, in contrast to poorly defined tight junctions seen in standard cell culture.
Unlike Caco-2 models, the Duodenum Intestine-Chip closely resembles in vivo duodenal epithelium cytoarchitecture, including well-polarized and cobblestone-like morphology, villi-like structures, and a well-developed continuous brush border with densely packed microvilli.