To better understand our organs and perform tests on a more human-like proxy, researchers are increasingly turning to organoids: miniaturized tissue cultures, usually in the form of organs, that are made from stem cells.
And a recent study, published in the journal Nature Biotechnology, may have just pushed the envelope by growing organoid human intestines with a working immune response inside mice.
"The largest part of the immune system in humans is the GI tract, and our biggest exposure to the world is what we put in our mouth," Michael Helmrath, a pediatric surgeon specializing in intestinal diseases at the Cincinnati Children’s Hospital Medical Center, told Wired in an interview.
Helmrath and his team had already managed to grow an intestinal organoid in a petri dish as part of a 2010 study, but this time around, they need one to "become more like human tissue," according to Helmrath.
They started by growing the organoid with human-derived stem cells, which they induced into becoming intestinal cells. These, in turn, eventually formed into tiny spheres of tissue.
Mice genetically engineered not to reject foreign cells served as the organoid recipients. The researchers first supplied the mice with human blood containing stem cells, then transplanted the organoid tissues near the kidneys, though without connecting them to the mice's digestive tracts.
Four months later, the organoids were pea-sized and with a similar population of human immune cells to those found in an actual human gut, Helmrath said. But the intestines didn't just look the part, they also acted the part — at least when it comes to protecting the body against bacteria.
When the researchers exposed the organoids to e. coli, the imitation intestines successfully produced immune cells indicating that it detected the presence of foreign bacteria, according to Helmrath.
That's a good sign for organoid research going forward. Helmrath and his team's findings show that the organoids, even when transplanted in a different animal's bodies, have a similar enough immune cell composition to more or less simulate an actual human gut's immune response. That will, no doubt, prove incredibly useful in testing all sorts of substances in the body, ranging from bacteria like e. coli to man-made drugs.
"It's incredibly important that when we are trying to create these platforms for testing drug efficacy and drug side effects in human tissue models that we actually make sure that we are as close to, and as complete as, the tissue in which the drug will work eventually in our human body," Pradipta Ghosh, a gastroenterologist at the University of California San Diego School of Medicine who was not involved in the study, told Wired. "So, adding the immune system is an important part of that."
Helmrath and his team, on the other hand, are more optimistic about using their organoids to treat those with malaffected digestive systems caused by genetic disorders, cancer, or disease — or even using them to grow new organ tissue inside a person to heal damaged ones.
More on organoids: Blobs of Human Brain Implanted in Rat Brains Replace Damaged Vision Functionality