Category Archives: 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

When it comes to new tumor-fighting treatments, its often as much about location, location, location as it is the actual drug interaction. Cytoxin-producing stem cells produced by scientists at Harvard University lodge at the site of brain tumor removal to continually attack remaining tumor cells. As an alternative to drug treatments that can be invasive or ineffective, the researchers saw promising results against glioblastomas, which hold the dubious distinction of being the most common and most fatal brain cancer.

When surgery is performed to remove a brain tumor, tumor cells are left behind. The common course of treatment to eradicate those remaining cells involves inserting a catheter directly into the brain to dispenses drugs which would otherwise not make it through the blood-brain barrier. However, one particular toxin, Pseudomonas exotoxin (PE), while effective and tolerated by humans, has a very short half-life and when washed over the area where the tumor was removed, degrades before significant interaction occurs with the target cells.

The research team under the direction of Khalid Shah instead created stem cells that were capable of independently producing this cytotoxin. Prior to this research, PE and other toxins had been engineered to not enter (and thus subsequently destroy) any human cells they came into contact with. However, Shahs stem cells would need to have this resistance when the toxin was by design already inside the cell.

After genetically constructing a stem cell that produced a toxin that it also could resist, the next design trick involved encapsulating those cells inside a gel matrix that the lab had previously used to test other tumor-fighting techniques. Their previous research found that the matrix kept the cells and resulting toxins in close proximity to the tumor cells.

This cell-doped gel can then be placed within the cavity created when a tumor is removed and could potentially remove the need to insert catheters for recurring drug treatments. To test this technique, mice first were given different strains of glioblastomas, which is important because not all strains respond in the same way to treatments. Researchers then removed the tumors and inserted the stem cell matrix.

When mice treated in this fashion were compared with those who received the same drug via catheter, and those mice who only had surgery, median survival for those three groups fell out significantly in favor of the stem cell group at 79 days versus 48 for those receiving catheter treatment, and 26 for the control. Additionally, no tumors regrew in those mice with the stem cell matrix, a result not seen in the other groups.

The treatment could have some promising applications, such as engineering cells to dispense multiple toxins, or even based directly off the patients tumor. Shah predicts there could be clinical trials for this technique within five years.

The research was originally published in the journal Stem Cells.

Source: Harvard University

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Toxin-producing stem cells fight brain tumors where it matters most

A group of scientists from Harvard University say they have discovered a major breakthrough in the fight against brain cancer.

The team said Friday it has successfully engineered stem cells to produce toxins that can kill cancerous cells, turning them into lethal weapons in the war against brain tumours.

The scientists say the stem cells will not only kill cancerous cells but also do it without harming themselves or surrounding healthy cells.

Now, we have toxin-resistant stem cells that can make and release cancer-killing drugs, Khalid Shah, a co-author of the study, said in a statement. Cancer-killing toxins have been used with great success in a variety of blood cancers, but they dont work as well in solid tumors because the cancers arent as accessible and the toxins have a short half-life.

Based on experiments conducted on mice, the results were positive, Shah said.

Nell Barrie of Cancer Research U.K., told BBC News that more work is needed to see whether the treatment works on humans.

But, she added, We urgently need better treatments for brain tumors, and this could help direct treatment to exactly where its needed.

The Harvard study was published online in the journal Stem Cells.

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Researchers say they have developed stem cells that can kill brain cancer

In a study that will provide the foundation for scientists to better replicate natural stem cell development in an artificial environment, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Guoping Fan, professor of human genetics, have established a benchmarking standard to assess how culture conditions used to procure stem cells in the lab compare to those found in the human embryo.

The study was published online ahead of print in the journal Cell Stem Cell.

Pluripotent stem cells (PSCs) are cells that can transform into almost any cell in the human body. Scientists have long cultured PSCs in the laboratory (in vitro) using many different methods and under a variety of conditions. Though it has been known that culture techniques can affect what kind of cells PSCs eventually become, no "gold standard" has yet been established to help scientists determine how the artificial environment can better replicate that found in a natural state (in vivo).

Dr. Kevin Huang, postdoctoral fellow in the lab of Dr. Fan and a lead author of the study, analyzed data from multiple existing research studies conducted over the past year. These previously published studies used different culture methods newly developed in vitro in the hopes of coaxing human stem cells into a type of pluripotency that is in a primitive or ground-zero state.

Utilizing recently-published gene expression profiles of human preimplantation embryos as the benchmark to analyze the data, Dr. Huang and colleagues found that culture conditions do affect how genes are expressed in PSCs, and that the newer generation culture methods appear to better resemble those found in the natural environment of developing embryos. This work lays the foundation on the adoption of standardized protocol amongst the scientific community.

"By making an objective assessment of these different laboratory techniques, we found that some may have more of an edge over others in better replicating a natural state," said Dr. Huang. "When you have culture conditions that more consistently match a non-artificial environment, you have the potential for a much better reflection of what is going on in actual human development."

With these findings, Dr. Fan's lab hopes to encourage further investigation into other cell characteristics and molecular markers that determine the effectiveness of culture conditions on the proliferation and self-renewal of PSCs.

"We hope this work will help the research community to reach a consensus to quality-control human pluripotent stem cells," said Dr. Fan.

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Benchmark proposed to better replicate natural stem cell development in the laboratory environment

Harvard Stem Cell Institute scientists at Massachusetts General Hospital have devised a new way to use stem cells in the fight against brain cancer. A team led by neuroscientist Khalid Shah, MS, PhD, who recently demonstrated the value of stem cells loaded with cancer-killing herpes viruses, now has a way to genetically engineer stem cells so that they can produce and secrete tumor-killing toxins.

In the AlphaMed Press journal Stem Cells, Shah's team shows how the toxin-secreting stem cells can be used to eradicate cancer cells remaining in mouse brains after their main tumor has been removed. The stem cells are placed at the site encapsulated in a biodegradable gel. This method solves the delivery issue that probably led to the failure of recent clinical trials aimed at delivering purified cancer-killing toxins into patients' brains. Shah and his team are currently pursuing FDA approval to bring this and other stem cell approaches developed by them to clinical trials.

"Cancer-killing toxins have been used with great success in a variety of blood cancers, but they don't work as well in solid tumors because the cancers aren't as accessible and the toxins have a short half-life," said Shah, who directs the Molecular Neurotherapy and Imaging Lab at Massachusetts General Hospital and Harvard Medical School.

"A few years ago we recognized that stem cells could be used to continuously deliver these therapeutic toxins to tumors in the brain, but first we needed to genetically engineer stem cells that could resist being killed themselves by the toxins," he said. "Now, we have toxin-resistant stem cells that can make and release cancer-killing drugs."

Cytotoxins are deadly to all cells, but since the late 1990s, researchers have been able to tag toxins in such a way that they only enter cancer cells with specific surface molecules; making it possible to get a toxin into a cancer cell without posing a risk to normal cells. Once inside of a cell, the toxin disrupts the cell's ability to make proteins and, within days, the cell starts to die.

Shah's stem cells escape this fate because they are made with a mutation that doesn't allow the toxin to act inside the cell. The toxin-resistant stem cells also have an extra bit of genetic code that allows them to make and secrete the toxins. Any cancer cells that these toxins encounter do not have this natural defense and therefore die. Shah and his team induced toxin resistance in human neural stem cells and subsequently engineered them to produce targeted toxins.

"We tested these stem cells in a clinically relevant mouse model of brain cancer, where you resect the tumors and then implant the stem cells encapsulated in a gel into the resection cavity," Shah said. "After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumors, we do see the toxins kill the cancer cells and eventually prolonging the survival in animal models of resected brain tumors."

Shah next plans to rationally combine the toxin-secreting stem cells with a number of different therapeutic stem cells developed by his team to further enhance their positive results in mouse models of glioblastoma, the most common brain tumor in human adults. Shah predicts that he will bring these therapies into clinical trials within the next five years.

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Toxin-secreting stem cells treat brain tumors, in mice

UC San Diego has been named an "alpha clinic" for the clinical study of stem cells, and the distinction comes with $8 million in research grants.

Stem cell therapies represent a new way of treating disease by regenerating damaged tissues and organs. Spokesmen for the UCSD school of medicine say the alpha clinic will focus on clinical trials in humans, not just basic research based on animals.

The decision to make UCSD an alpha clinic was announced Friday by the California Institute for Regenerative Medicine, which was created by California voters after they approved $3 billion for stem cell funding in 2004.

Everything we do has one simple goal, to accelerate the development of successful treatments for people in need, said C. Randal Mills, CIRM president and CEO.

Catriona Jamieson, professor of medicine at UC San Diego School of Medicine, is the alpha clinic grants principal investigator. She said the clinic will provide needed infrastructure for first-in-human stem cell-related clinical trials.

"It will attract patients, funding agencies and study sponsors to participate in, support and accelerate novel stem cell clinical trials and ancillary studies for a range of arduous diseases, Jamieson said.

The university has already announced human stem cell trials, aimed at treating spinal chord injuries, leukemia and type-1 diabetes.

UCSD spokesmen said researchers are conducting those trials using fetal and embryonic stems cells, as well as stem cells made from reprogramming skin cells.

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UCSD Gets $8 Million For Stem Cell Research

Using stem cells from blood, researchers have been able to grow blood vessels in a week.REUTERS

Researchers at Sahlgrenska University Hospital in Sweden have been successful in transplanting blood vessels made from three spoons of blood.

Two years ago two patients at the hospital received the blood vessels made from stem cellsin the blood.

Earlier, another patient too was treated using blood vessels made by her stem cells but in that case, the researchers had to drill into the bone marrow to obtain the stem cells.

In the later cases, all they needed was three spoons of the patient's blood and a waiting period of a week.

The children did not have the vein that goes from the gastrointestinal tract to the liver. This was rectified using the new blood vessels, a treatment that holds out promise for people with varicose veins and myocardial infarction.

The method also rules out rejection normally accompanying any foreign body transplant.

Professors Olausson and Sumitran-Holgersson have treated three patients so far. Two of the three patients are still doing well and have veins that are functioning well.

They now hope to be able to grow complete organs to overcome organ shortage from donors.

Use of embryonic stem cells to treat macular dystrophy and degeneration has been proven to be safewith low rejection rates.

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Blood Vessels Made from Three Spoons of Blood in a Week's Time