Intestinal organoids created from human induced pluripotent stem cells (hiPSC) are valuable tools for studying developmental biology and potential personalized therapies, but their closed topology and relatively immature state can limit their uses. Moerkens and the team applied organ-on-chip technology to develop a hiPSC-derived intestinal barrier that gives researchers access to the apical and basolateral sides of the tissue in an in vitro microenvironment mimicking the physiological conditions in the body. To replicate the growth factor gradients along the crypt-villus axis, they exposed the cells to expansion and differentiation media. Under these conditions, the intestinal epithelial cells self-organized into villus-like folds with physiological barrier integrity. Remarkably, the team also observed that myofibroblasts and neurons emerged and formed a subepithelial tissue in the bottom channel of the chip.
The growth factor gradients applied efficiently balance dividing and mature cell types and induce an intestinal epithelial layer cell composition that resembles that of the human small intestine, including absorptive and secretory cell lineages. This small intestine-on-chip system was set up as a model to study celiac disease. By starting with patient-derived cells, the researchers capture the complex genetic background involved in celiac disease and create a personalized system to study how the celiac gut differs from that of controls.
The gut-in-chip system that the group has established can easily be adapted to study other physiological processes in the small intestine, including drug metabolism and digestion, and a model resembling the large intestine can be developed by tweaking the differentiation protocols.
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