What if we could recreate the complexity of human disease, like inflammatory bowel disease (IBD), in a lab dish? That’s exactly what researchers at i3S are doing through advanced 3D in vitro models. In this blog post, based on their recent scientific publication, Catarina Leite Pereira walks us through how these models offer a more realistic and powerful way to study IBD and test new treatments.
This piece is part of GENEGUT’s ongoing effort to bridge the gap between scientific discovery and public understanding. It highlights how cutting-edge laboratory research can have a real-world impact on how we treat chronic illnesses. Whether you’re new to the topic or already familiar with IBD, this post offers a clear and engaging look at how innovative tools are transforming biomedical research.
Establishment of a 3D multi-layered in vitro model of inflammatory bowel disease
Author: Catarina Leite Pereira
Scientists often use lab-grown cell systems, called in vitro models, to study diseases like IBD and to test new treatments. These models help us understand how the disease works and how new therapeutic approaches might help. However, the traditional models—where cells grow in flat layers (2D)—don’t do not fully recapitulate how things work inside the human body. In real tissues, cells grow in three dimensions, interact with each other in complex ways, and sit within a specific tissue structure that’s hard to mimic on a flat surface.
One commonly used cell line is called Caco-2, which comes from a type of colon cancer. It’s often used to study how substances move across the intestinal wall. Some researchers have tried to improve these models by growing different types of cells together—like gut cells and immune cells—but even then, they’re often kept in separate areas, so the interactions are limited. A few have placed them together in the same space, or flipped the setup to encourage better interaction, but it’s still far from perfect.
That’s why 3D models are becoming more popular. These models let cells grow in all directions, more like they do in the human body, and allow better communication between cells and their surroundings. To build these 3D environments, scientists can use materials called scaffolds or gels, which mimic the natural support structure around cells. One of the most commonly used materials is collagen. Collagen it’s affordable, easy to work with, and behaves very similarly to the natural environment inside the body. Other materials, like alginate and even tissue extracted from organs, can also be used.
Recently, researchers have developed several types of 3D gut models—including ones based on gels and scaffolds, as well as more advanced versions like gut-on-a-chip and organoids. These newer systems are helping to close the gap between simple cell cultures and animal studies. Our team at i3S has proposed a more advanced 3D model of the intestine specifically to study IBD. We have previously built a 3D model that mimics how drugs are absorbed in the gut, including different layers: an epithelial layer (the cells lining the gut), a collagen-based middle layer with fibroblasts (support cells), and an endothelial layer to simulate blood vessels. To study IBD more realistically, we added immune cells, especially macrophages, which are important because they help drive the inflammation seen in the gut during the disease. We also treated the 3D model with a special mix of molecules that trigger inflammation, to better mimic what happens in the intestines of IBD patients.
With these additions, our improved 3D model gives a much more accurate picture of what’s going on inside the gut during IBD, while providing a more accurate and consistent tool to test new therapeutic approaches before moving on to animal or human testing. Our model helps researchers understand how inflammation affects molecules absorption and how well different treatments might work. Most importantly, it plays a big role in the GENEGUT project as a testing platform to check if the new nano-based treatments we’re developing are safe and effective in IBD treatment.
UK participants in Horizon Europe Project GENEGUT are supported by UKRI grant number 10042451 (Bangor University).