Using pluripotent stem cells researchers have been able to build a mini stomach in the lab.REUTERS

In a first, a miniature stomach was created in the lab by scientists using stem cells.

Pluripotent stem cells that can grow into any cell type were used by scientists at Cincinnati Children's Hospital Medical Center to generate the artificial stomach.

The scientists identified the steps in stomach formation in the human embryo and by manipulating these in a petri dishwere able to coax the stem cells to form a mini stomachmeasuring 3 mm in diameter.

They then studied how h.pylori bacteria affected stomach tissues and spread rapidly. The bacteria is responsible for peptic ulcer and stomach cancer.

This first-time molecular generation of a 3D human stomach (called gastric organoid) presents new opportunities for drug discovery, modelling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes, according to Jim Wells, PhD, principal investigator and a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's.

The work was conducted in collaboration with researchers at the University of Cincinnati College of Medicine.

The discovery of how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition is important as mouse models are sometimes not the best fit when studying human ailments, the team said.

The human gastric organoids will be useful to identify biochemical processes in the gut that allow gastric-bypass patients to become diabetes-free soon after surgery before losing significant weight.

Obesity fuelled diabetes and metabolic syndrome are public health challenges, addressing which has been difficult due to lack of reliable laboratory modelling systems.

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Human Stomach Made in the Lab Using Stem Cells

CINCINNATI, Oct. 29 (UPI) -- The race to treat and cure the vast range of diseases affecting the human stomach, from cancer to diabetes, has received a boost, thanks to researchers at Cincinnati Children's. In a study published this week in the journal Nature, scientists say they were able to successfully construct miniature human stomachs using stem cells.

Lab-built organs, researchers say, can help medical researchers better observe organ-specific malfunctions and potentially test remedies with more predictive and reliable results. The mini stomachs, created in the Cincinnati lab, are the first examples of three-dimensional human stomach tissue created from pluripotent stem cells -- stem cells that can be programmed to form any type of human cell.

"Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs)," lead researcher Jim Wells said in a press release. "In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition."

The key to building any type of organ tissue from stem cells, is understanding the formation of the organ in the embryonic stage of natural human development. Once properly understood, the process can be replicated by manipulating stem cells in a petri dish. And that's exactly what scientists were recently able to do, coaxing pluripotent stem cells into transforming into stomach tissue.

Researchers have already used the mini stomachs to absorb the behavior of H. pylori bacteria, which causes stomach inflammation and can lead to peptic ulcer disease and stomach cancer.

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Scientists generate human stomach tissue using stem cells

Miniature human stomachs have been created from stem cells which could be used to study gastric diseases and develop new treatments in future.

The 3mm-wide hollow "organoids" have a complex 3D structure and are lined with various kinds of functioning cells mimicking those of a real stomach.

In tests, scientists used the tiny stomachs to study infection by Helicobacter pylori, the bacteria linked to peptic ulcers and stomach cancer.

The organoids potentially offer a better way to study human stomach diseases and drug treatments than animals, whose gut physiology is unlike that of humans.

Lead researcher Dr James Wells, from Cincinnati Children's Hospital Medical Center in the US, said: "The breakthrough that we've achieved is we can now generate fully in a petri dish stomach tissue.

"This is important because in the case of people with stomach disease like peptic ulcer disease, or ultimately people who get stomach cancer, we can now study the very early stages of that disease, and then use this as a research tool to try and identify therapies to prevent stomach disease.

"Up until now there's been no good way to study stomach diseases in humans. Human stomach is very different than the stomach of other animals.

"The different cells and their structure and arrangement in our stomach tissues in a dish were virtually identical to that which you would find in a stomach normally."

It may even be possible to generate tissue for plugging holes in the stomach caused by disease, he said.

The organoids were created from human "pluripotent" stem cells, typically originating from early-stage embryos, which have the ability to develop into virtually any kind of tissue.

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Mini human 'stomachs' created from stem cells

A CT scan of a human abdomen with stomach cancer. Photograph: Bojan Fatur/Getty Images

Scientists have grown miniature human stomachs from stem cells as a way of studying gastric diseases such as ulcers and stomach cancer and in the future creating tissue to repair patients stomachs.

The mini-stomachs are grown in petri dishes from stem cells. Fully formed, they are the size of a pea and shaped like a rugby ball. They are hollow with an interior lining that is folded into glands and pits like a real stomach.

Crucially, the researchers found that the miniature stomachs, known as gastric organoids, respond to infection very much like ordinary human stomachs.

There hasnt been any good way to study human stomach disease before because animals just dont get the same diseases, said James Wells, director of the Pluripotent Stem Cell Facility, Cincinnati Childrens Hospital Medical Center, who led the research which is published in Nature.

Human gastric diseases are associated with chronic infection by the bacterium Helicobacter pylori. Half the worlds population is infected with the bug, which can be picked up from food. Although most people do not show symptoms, once the infection is present up to 20% of carriers will develop gastric ulcers during their lifetimes. Around 2% will develop stomach cancer.

In developing countries, where H. pylori infection is more prevalent, gastric cancers are the second leading cause of cancer-related deaths.

Having grown the mini-stomachs, the researchers then injected them with H. pylori. In animals, H. pylori has little effect and disease does not follow but in the gastric organoid, the invading bacteria behaved as if it were a real human stomach.

The bacteria began injecting their proteins into the surrounding cells, and started to multiply. This is the hallmark of infection, said Wells. We can now very effectively study the bacteria and how it generates diseases. This has never been possible before with human tissue in vitro.

This is not the first time that miniature organs have been grown from stem cells. In 2013, scientists grew miniature kidneys and successfully transplanted into a rat. Replacement windpipes, grown from stem cells on lab-made scaffolds, have also been grown and transplanted into patients.

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Scientists grow miniature human stomachs from stem cells

Scientists have grown miniature stomachs in a lab dish using stem cells, and are already using them to study stomach cancer. They hope they can grow patches to fix ulcers, find new drugs to treat and even prevent stomach cancer, and perhaps even grow replacement stomachs some day.

They discovered that the bacteria that cause stomach cancer begin doing their dirty work almost immediately, attaching to the stomach lining and causing tumors to start growing in response. Helicobacter pylori causes many, if not most, cases of stomach cancer, which affects more than 22,000 Americans a year and kills half of them. Stomach cancer is a major killer globally, affecting close to a million people a year and killing more than 70 percent of them.

And the team grew their mini-stomachs using two different types of stem cells human embryonic stem cells, grown from very early human embryos, but also induced pluripotent stem cells or iPS cells, which are made by tricking bits of skin or other tissue into acting like a stem cell.

In our hands they worked exactly the same, James Wells of Cincinnati Childrens Hospital Medical Center, who led the research. Both were able to generate, in a petri dish, human stomach tissue.

Immunofluorescent image of human stomach tissue made using stem cells

Stem cells are the body's master cells. Embryonic stem cells and iPS cells are both pluripotent meaning they can give rise to any tissue in the body. They've been used to grow miniature human livers, retinas, brain tissue and have been injected into eyes to treat eye disease.

Growing anything close to a real stomach or even a patch for an ulcer is a long way off. The gastric organoids Wellss team made the name up are just about the size of a BB bullet.

Its not easy getting stem cells to do what you want them to do. Wells and his team, including graduate student Kyle McCracken, had to use various growth factors and chemicals, each introduced at precisely the right time, to coax the cells into becoming three-dimensional blobs of stomach tissue. The stomach is a complex organ, with layers of muscle cells, cells that make up the stomach lining and glands that secrete proteins and acid to digest food.

"The bacteria immediately know what to do and they behaved as if they were in the stomach.

But the process worked, and the mini-stomachs look just like stomach tissue, the team reports in this weeks issue of the journal Nature.

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Mini-Stomachs Let Scientists Study Ulcers in a Lab Dish