Re-creating the human intestine at microscale: using induced pluripotent stem cells and organ-on-chip systems

The research models used to study the human intestine are crucial for improving our understanding of intestinal diseases, the effects of gut bacteria and why certain individuals respond differently to nutrients or drugs. Traditional research models like cell lines cultured in plastic dishes and mice fail to fully replicate human intestinal biology and disease because they are either too simplistic (cell lines) or show species-specific differences (mice and other animals).

In this thesis we developed an intestine-on-chip: a miniature version of the human intestine, only a few centimeters in length. The chip creates an environment resembling our intestine, including continuous fluid flow. This dynamic environment drives the intestinal cells to form finger-like structures that mimic intestinal villi. The cells in the intestine-on-chip are also special—instead of using cells taken directly from the human intestine, we used cells from urine. By activating the right genes and exposing the cells to various growth factors for several months, we transformed them into (induced pluripotent) stem cells and then into intestinal cells. This allows the generation of personalized mini-intestines from non-invasive sources.

This intestine-on-chip system mimics the intestinal epithelial barrier and subepithelial tissues, and we optimized it to reproduce a human-like cell composition and structure. We could also show that the chip’s dynamic environment promotes more mature and functional intestinal phenotypes compared to conventional static models. This thoroughly characterized intestine-on-chip system holds great promise for modelling intestinal diseases, studying specific genetic profiles and cell types, facilitating drug testing and analyzing nutrient and drug metabolism and absorption.