Researchers at Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland have developed a mini intestine on a chip that closely mimics the morphology and cellular composition of the small intestine. The device could be useful for advancing personalized medicine, drug screening, and even paving the way for researchers to grow new tissues and organs in the lab for use in regenerative medicine.
Creating organoids typically involves assembling stem cells to form miniature versions of tissues or organs. However, existing approaches are limited in how closely they can mimic native human tissues, and researchers have not yet mastered how to control and guide the movement and growth of cells. Often the cells will self-assemble into sphere-like structures with limited viability and little resemblance to the tissue of choice.
In this most recent attempt, the Swiss researchers have used a gut shaped template, laser-sculpted within a hydrogel in a microfluidic channel, to guide stem cells into the correct tissue arrangement that mimics the small intestine. The hydrogel scaffold includes crypt-like structures, just like those found in the intestine.
To the researchers’ surprise, the cells appeared to arrange themselves correctly when first introduced to the structure without any guidance, and began differentiating into cell types found at specific locations within the intestine, including rare cells only found within the intestinal crypts. The shape and composition of the hydrogel were enough to prompt the cells to act like intestinal cells.
“It looks like the geometry of the hydrogel scaffold, with its crypt-shaped cavities, directly influences the behavior of the stem cells so that they are maintained in the cavities and differentiate in the areas outside, just like in the native tissue,” said Matthias Lütolf, a researcher involved in the study.
Interestingly, the new organoids appear to allow for high cell turnover that are found in the gut, whereby dead cells are removed and new cells are created by stem cells within the crypts. “The introduction of a microfluidic system allowed us to efficiently perfuse these mini-guts and establish a long-lived homeostatic organoid system in which cell birth and death are balanced,” said Mike Nikolaev, another researcher involved in the study.
Although the current organoids mimic the intestine, similar approaches could be used to mimic other tissues. “Our work shows that tissue engineering can be used to control organoid development and build next-gen organoids with high physiological relevance, opening up exciting perspectives for disease modelling, drug discovery, diagnostics and regenerative medicine,” said Lütolf.
See a video about the technique below: