Scientists grow small human intestines inside mice

in your intestines obvious job: it processes the food you eat. But it has another important function: it protects you from bacteria, viruses, or allergens that you ingest with this food. “The biggest part of the human immune system is the gastrointestinal tract, and our biggest impact on the world is what we put in our mouths,” says Michael Helmrath, a pediatric surgeon at Cincinnati Children’s Hospital Medical Center, who treats patients with intestinal diseases. .

Sometimes this system malfunctions or does not develop properly, which can lead to gastrointestinal diseases such as ulcerative colitis, Crohn’s disease and celiac disease, which are on the rise worldwide. Studying these conditions in animals can tell us a lot, because their diets and immune systems are very different from ours.

In search of a better method, last week Helmrath and colleagues announced in Journal natural biotechnology that they transplanted tiny three-dimensional globules of human intestinal tissue into mice. Within weeks, key features of the human immune system had developed in these spheres, known as organelles. The model can be used to simulate the human intestinal system without having to experiment with sick patients.

This experiment is a dramatic follow-up to 2010, when Cincinnati Children’s researchers created the world’s first working gut organoid, but their original model was simpler version in laboratory glassware. A few years later, Helmrath says, they realized “we need to make it more like human tissue.”

Scientists elsewhere are growing similar miniatures of other human organs, including the brain, lungs and liver, to better understand how they develop normally and how things go wrong that lead to disease. Organoids are also used as human avatars for drug testing. Because they contain human cells and exhibit some of the same structures and functions as real organs, some researchers believe they are a better substitute for laboratory animals.

“It’s incredibly important that when we try to build these platforms for testing drug efficacy and drug side effects in human tissue models, we really make sure we’re as close and complete as the tissue that the drug will work in. eventually in our human body. So adding an immune system is an important part of that,” says Pradipta Ghosh, director of the Center of Excellence in Humanoid Research at UC San Diego School, which is developing human organoids for drug screening and testing. Gosh did not participate in the study.

To grow the organoid, the scientists started with induced pluripotent stem cells created from mature human cells taken from blood or skin. They have the ability to transform into any type of body tissue. By feeding the stem cells a special molecular cocktail, the team coaxed them into the intestinal cells. After growing in a dish for 28 days, the cells formed tissue spheres only a few millimeters in diameter.

The team carefully transplanted these spheres into mice that had been genetically engineered to suppress their own immune systems so that the organoid tissue would not be rejected. (The researchers transplanted an intestinal organoid near each mouse’s kidney, so it wasn’t actually connected to the animals’ digestive tract.) To stimulate the organoids to produce human immune cells, they previously gave mice human cord blood, a source of stem cells that can transform into the right cells. .