Science News - November 29, 2014

BODY & BRAIN
Tiny human intestines grown in mice
Gut tissue could help researchers tailor disease treatments

B Y MEGHAN ROSEN

Slimy chunks of human gut can now grow up and get to work inside of mice.

Transplanted into rodents, tiny balls of tissue balloon into thumbnail-sized nuggets that look and act like real human intestines, researchers report October 19 in Nature Medicine.

The work is the first time scientists have transformed stem cells into working bits of intestines in living animals. These bits could help tailor treatments for patients with bowel diseases, such as Crohn’s disease or colon cancer, says coauthor Michael Helmrath, a pediatric surgeon at Cincinnati Children’s Hospital Medical Center. Doctors could test drugs on the gut nuggets and see how a patient’s tissues respond without having to subject the person to different treatments.

“If you give me a patient, I can grow their intestines,” Helmrath says.

For decades, researchers have tried and failed to cultivate human gut tissue in the lab, says stem cell biologist Eduard Batlle of the Institute for Research in Biomedicine in Barcelona.

Transplanted fetal tissue can turn into something like intestines, but its use is ethically debatable and the tissue wouldn’t match up with a patient’s own. In recent years, scientists have started

Transplanted into mice, tiny specks of human intestinal tissue (stained pink) develop into working organs surrounded by a muscular sheath (stained green), just like real intestines.

to see glimmers of success in turning mature cells into organs. Using adult cells reprogrammed into stem cells, researchers have grown heart, liver and brain tissue (SN: 12/28/13, p. 20).

Still, converting clumps of tissue into 3-D organs remains a challenge — especially for organs with lots of different cell types. The intestine is a complicated structure, says UCLA stem cell biologist James Dunn. The muscular tube wriggles and writhes as food snakes through, while some of its cells ooze mucus, absorb nutrients and break down sugars.

In 2011, Helmrath’s colleagues created specks of human intestinal tissue from reprogrammed cells. The specks were like intestinal newborns: They didn’t behave quite like adults. Helmrath and colleagues thought transplanting the specks into a blood vessel–rich nook in mice might help the tissue mature.

The team created clumps of intestinal tissue from adult blood cells and then embedded them into gluey lumps of gel. Next, the researchers placed the lumps inside mouse abdomens underneath a filmy membrane that clings to the kidneys. When researchers peeked inside the mice six weeks later, the team discovered plump pink organs.

“We didn’t have any idea that it was going to grow and develop so beautifully,” Helmrath says.

In the mice, the tissue had bloomed
into organs 50 to 100 times their origi-
nal size. The squishy tubes could absorb
and digest food. They even responded to
major surgery as real intestines do. “This
is exciting work that’s going to move the
whole field forward,” Dunn says. “But
we’re still missing some elements.”
For one, the intestinal hunks live in an
odd home, on the kidney. And they lack
nerve cells, which prompt guts to clench
and move. Helmrath says his team is
working on the nerve cell problem.
“We’ve actually already figured it out,”
he says. “But that’s not for this paper.” s

in the Siberian man’s DNA. That makes sense, remarks paleogeneticist Morten Rasmussen of Stanford University, since Denisovan genes cluster among present-day Southeast Asians (SN: 9/22/12, p. 5).

Evidence that Neandertal interbreeding began no more than 60,000 years ago supports the idea that a wave of H. sapiens dispersed out of Africa around that time, occasionally mated with Neandertals and passed Neandertal DNA to human populations that led to all non-Africans today, says paleo-anthropologist Chris Stringer of the Natural History Museum in London.

Paleogeneticist Mattias Jakobsson of Sweden’s Uppsala University finds it intriguing that the Siberian man displays equal relatedness to present-day

Asians, a 24,000-year-old Siberian child and a 7,000-year-old Spanish hunter-gatherer (SN: 5/17/14, p. 26). Unlike Pääbo’s team, Jakobsson suspects the man belonged to a population that has yet to be pinned down but nonetheless helped give rise to current East Asians and Europeans. s

Woods Hole Oceanographic Institution in Massachusetts. But he cautions that it’s still unclear whether the plants can digest dangerous waste outside the lab.

Yao agrees. He plans to test the plants’ scrubbing potential in real-world conditions.

Strict regulations on genetically engineered plants in the United States and elsewhere may make these green cleaners difficult to use, says environmental scientist Sharon Doty of the University of Washington in Seattle. In her research on PAH remediation, Doty introduces whole bacteria instead of injecting bacterial genes. Called endophytes, these microbial partners live inside a plant, breaking down PAHs and other pollutants, she says.