Renée Moerkens and Joram Mooiweer
We are Renée Moerkens and Joram Mooiweer, PhD students at the Department of Genetics, University Medical Centre, Groningen, the Netherlands. As part of a national consortium—the Netherlands Organ-on-Chip Initiative (NOCI)—we are using Gut-on-Chip technology to study coeliac disease.
But what is Gut-on-Chip?
A Gut-on-Chip is a miniature version of a gut made by placing human gut barrier cells into a ‘chip’ - a small device approximately the size of a computer memory stick that contains a channel in which we can grow cells and add fluids. The chip creates a miniaturised environment that resembles our own gut, including peristaltic motions. These mechanical forces cause the cells in the channel to form finger like structures that resemble the villi in our intestine. In this way we can recreate a human gut in our laboratory and use it to perform experiments.
Cells from urine and blood
It is not just the chip system that makes this technology unique, the cells we use are rather special as well. The gut barrier cells we use to build our chips are not directly derived from a human gut, but made from cells found in urine or blood. This is possible because all cells in our body contain the same DNA and, by turning the right genes on and off, we can make a urine or blood cell into a stem cell. Cells created this way are called induced pluripotent stem cells and can develop into all the cell types of the body. These stem cells can then be turned into gut barrier cells by mimicking the natural environment of gut cells. In practice, this means adding a cocktail of different molecules, called growth factors, to the cells every day for about one and a half months. In this manner, and with a bit of patience, we can make gut cells in our laboratory in a non invasive way.
The Gut-on-Chip allows us to study diseases outside of the human body in a system that closely resembles the human gut. We are currently developing these small mini guts using cells from patients with coeliac disease so that we can study the effect of genetics on gut function in coeliac disease. We will first investigate whether the gut barrier is intact, or maybe a bit leaky, in patients with coeliac disease. We know that after intake of gluten, this gut barrier is heavily disrupted. However, it is unclear whether the barrier might already be mildly affected before exposure to gluten due to, for example, specific coeliac disease genetic risk factors. If this is the case, gluten peptides could more easily penetrate the intestinal barrier to reach the immune cells that reside underneath and trigger inflammation. Such a genetic defect could potentially be counteracted by treatments that strengthen this barrier and prevent gluten peptides from reaching immune cells.
The effect of the immune system and gut microbiome
Besides providing a coeliac disease model of the gut barrier, Gut-on-Chip also allows us to model other aspects of the disease because this chip provides a unique platform to integrate multiple cell types associated with coeliac disease. We know that the intestinal damage in coeliac patients is caused by a strong inflammatory response to gluten, which is caused by immune cells. On the chip we will be able to study this immune reaction by adding these immune cells to the intestinal barrier in the system. Moreover, we could even extend the model to include a patient’s gut microbiome by adding microbes to the chip.
We hope that such a multi-cellular model can help us answer fundamental questions about this complex disease, such as whether and how the microbiome contributes to disease development and if it is possible to change our microbiome composition to a more favourable one via diet. We may also be able to explore how the gut barrier communicates with the immune cells that eventually trigger damage. Using the miniature guts of coeliac disease patients in our lab, we hope to learn more about the processes that drives the disease and how to avoid or control them.
If you want to stay up to date on our progress you can follow us on Twitter (@nociorganonchip).