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.
With the same bacteria Yao’s group
used, willow shrubs and grass chewed
up phenanthrene in contaminated soil,
Doty’s team reports in the Oct. 21
Environmental Science & Technology. s H E