Scientists Simulate the Human GI Tract in Mice

(Image: Julien Tromeur/Unsplash) A team of biologists and pathologists in Ohio has successfully modeled the human gastrointestinal (GI) tract in rodents. By planting tiny balls of human intestinal tissue into the abdomens of mice and allowing those tissues to take root, the scientists have created a working environment in which they can study GI physiology and immunology without human test subjects.

Their achievement was published late last month in the journal Nature Biotechnology. The scientists, who hail from the University of Cincinnati’s Scientists Mimic the Human GI Tract in Mice and the Cincinnati Children’s Hospital, began with pluripotent stem cells. Thanks to pluripotent stem cells’ ability to become any bodily cell, the team could “feed” them a specific growth protein until they became intestinal cells. In less than a month, these cells had formed tiny balls of tissue known as organoids.

Next, the team used Busulfan (a common chemotherapy drug) and genetic engineering to suppress the immune systems of their test mice. This would ensure the lab-grown organoids wouldn’t be rejected. The scientists transplanted one organoid next to each test mouse’s kidneys, then monitored the organoids’ growth over the span of 20 weeks. By the end of this period, the organoids had grown to the size of a pea. Better yet, they contained roughly 20 types of human immune cells, mimicking the immune population in the human GI tract.

(Image: Bouffi et al/Nature Biotechnology 10.1038/s41587-022-01558-x)

The human gut might be known for its digestive capabilities, but it also helps the body defend against disease. Any bacteria found in the food we eat or the water we drink must eventually answer to the defense mechanisms found in the gut’s tissues and layers of mucus, which make up the body’s largest immune component. While human intestinal organoids (HIOs) kept in the petri dish have historically provided scientists with a helpful model for exploring human intestinal physiology, they haven’t possessed the immune components necessary to facilitate the study of GI disease.

The Cincinnati team’s work changes that. Exposing their transplanted organoids to E. Coli bacteria prompted the tissues to produce M cells, which carry out immune functions in the lining of the intestine. M cells are known to populate following infection and inflammation, suggesting that the in vivo mouse model could serve as a valuable test environment for pathology-related experiments. In the future, scientists might be able to use their model to study the origins of food allergies, intestinal infection, and gut inflammation—an effort that could prove doubly useful if the Cincinnati team makes their organoids from individual patients’ cells, which they plan to attempt soon.

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