Maxime M. Mahe INSERM/CCHMC

Lab-created ‘miniguts’ grow larger when you load them with springs

Scientists around the world are harnessing organoids, tissue clusters derived from stem cells that mimic the 3D structure of our organs in miniature, to model diseases and test new drugs. But most organoids are nowhere near large and complex enough to replace missing or damaged parts of human organs. In a new study, researchers have shown that adding loaded springs to human gut organoids may make them grow bigger and exhibit features of adult organs as they mature in the abdomens of mice.

As our intestines develop, they’re pulled and stretched inside the body; previous studies have shown that those forces influence their emerging structure. So the researchers aimed to apply similar forces to intestinal tissue grown from human stem cells that had been developing for 10 weeks inside of mice. Each was implanted with a spring about 1 centimeter long, compressed inside a gelatin capsule that gradually dissolved to let loose the spring’s outward force.

The organoids were almost twice as large as their springless counterparts—1.2 centimeters versus 0.5 centimeters—and they had features of a functional intestine that more closely resembled samples of adult tissue, the team reports online today in Nature Biomedical Engineering. For example, the organoids grew taller fingerlike projections, known as villi, on their surfaces (above), and thicker, less permeable layers of tissue. They also showed higher expression of certain genes involved in the development of the digestive tract.

The resulting organoids won’t be ready to replace segments of missing or injured intestine any time soon. But the researchers suggest that in a larger host animal, the technique might someday generate transplantable human tissue. They’re now trying it out in pigs.