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First human mini stomach developed with stem cells; to help treat stomach cancer

Part of a miniature stomach grown in the lab, stained to reveal various cells found in normal human stomachs. (Photo: Nature)

Part of a miniature stomach grown in the lab, stained to reveal various cells found in normal human stomachs. (Photo: Nature)

Moving over from artificially induced tubes int stomach for feeding while seriously ill, externally grown miniature stomachs in the lab will replace the tubes inside your body, going by the latest successful stem cell innovation.

Scientists at Stanford University in California have grown miniature stomachs in the lab from human stem cells, just like it grows 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, said researchers in an article published in Nature magazine this week.

The paper shows how cells in human embryos morph into organs, which scientists call ‘gastric organoids’, which in turn can help understand diseases such as cancer, and to test the stomach’s response to drugs in future.

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

The stem cells used are pluripotent, or plastic and 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 or 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, said the research report.

When the stem cells were 3 days old, researchers added a mix of proteins including Noggin, which suppresses that pathway, and timed doses of retinoic acid, a compound in vitamin A. After 9 days, the cells were left to grow in a protein bath. In 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 was similar to their control tissues, which the team took from mice. In a way, they “are remarkably similar to an actual stomach”, says lead author James Wells at Cincinnati Children’s Hospital Medical Center in Ohio.

Next, the researchers used 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, says growing thousands of such organoids will help study human genetics in future and plans to be able to grow personal stomach tissue to patch up ulcers in humans.

Wells and some colleagues are already attempting to use human organoids to plug stomach holes in mice.

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