The artificial human guts could be used to study diseases and test drug treatments.


Scientists have successfully grown miniature stomachs in the lab
from human stem cells, guiding them through the stages of
development seen in an embryo.

The lumps of living tissue,
which are no bigger than a sesame seed, have a gland structure
that is similar to human stomachs and can even harbour gut
bacteria.

The feat, reported in this week's Nature, offers a window to how
cells in human embryos morph into organs. Scientists say that
these 'gastric organoids' could also be used to understand
diseases such as cancer, and to test the stomach's response to
drugs.

“This is extremely exciting,” says Calvin Kuo, a stem-cell biologist
at Stanford University in California. “To be able to recapitulate that
in a dish is quite a technical achievement.”

The stem cells used to grow the mini stomachs are pluripotent, or
plastic: given the right environment, they can mature into any
type of cell. But to coax them down a specific path in the lab
requires recreating the precise sequence and timing of
environmental cues in the womb — the signals from proteins and
hormones that tell cells what kind of tissue to become. Bits of
kidney, liver, brain and intestine have previously been grown in a
lab dish using this technique.


Stomach switch

The key to turning pluripotent stem cells into stomach cells was a
pathway of interactions that acts as a switch between growing
tissues in the intestine and in the antrum, a part of the stomach
near its outlet to the small intestine.

When the stem cells were around three days old, researchers
added a cocktail of proteins including Noggin, which suppresses
that pathway, and timed doses of retinoic acid, a compound in
vitamin A. After nine days, the cells were left to grow in a protein
bath.

At 34 days, the resulting organoids were only a few millimetres in
diameter and had no blood cells, immune cells, nor the ability to
process food or secrete bile. But their gland structures and each
marker of their development paralleled development in their
control tissues, which the team obtained from mice. In that sense,
they “are remarkably similar to an actual stomach”, says study
leader James Wells, a developmental biologist at Cincinnati
Children's Hospital Medical Center in Ohio.

That similarity allowed the researchers to use the tiny stomachs as
test subjects for human disease by injecting them
with Helicobacter pylori, a bacterium that targets the antrum and
can cause ulcers and stomach cancer. Within 24 hours, the team
found that H. pylori was causing the organoid cells to divide twice
as fast as normal, and activating a particular gene, c-Met, that can
cause tumours. These effects are also seen in human stomachs
infected with H. pylori.

The researchers say that they can grow the stomach organoids
from both embryonic stem cells and skin cells induced to
pluripotency. Jason Mills, a gastrointestinal pathologist at
Washington University School of Medicine in St. Louis, envisions
growing thousands of such organoids, each from a different
person’s cells, and infecting them with a pathogen to study the
role of individual genetics.

Wells says that his team's long-term goal is to be able to grow
personal stomach tissue to patch up ulcers in humans. He and
some colleagues are already attempting to use human organoids
to plug stomach holes in mice.