Category Archives: Stem Cells

12 hours ago Stem cells show auxeticity; the nucleus expands, rather than thins, when it's stretched. Credit: Effigos AG

Looking at stem cells through physicists' eyes is challenging some of our basic assumptions about the body's master cells.

One of the many mysteries surrounding stem cells is how the constantly regenerating cells in adults, such as those in skin, are able to achieve the delicate balance between self-renewal and differentiation in other words, both maintaining their numbers and producing cells that are more specialised to replace those that are used up or damaged.

"What all of us want to understand is how stem cells decide to make and maintain a body plan," said Dr Kevin Chalut, a Cambridge physicist who moved his lab to the University's Wellcome Trust-MRC Cambridge Stem Cell Institute two years ago. "How do they decide whether they're going to differentiate or stay a stem cell in order to replenish tissue? We have discovered a lot about stem cells, but at this point nobody can tell you exactly how they maintain that balance."

To unravel this mystery, both Chalut and another physicist, Professor Ben Simons, are bringing a fresh perspective to the biologists' work. Looking at problems through the lens of a physicist helps them untangle many of the complex datasets associated with stem cell research. It also, they say, makes them unafraid to ask questions that some biologists might consider 'heretical', such as whether a few simple rules describe stem cells. "As physicists, we're very used to the idea that complex systems have emergent behaviour that may be described by simple rules," explained Simons.

What they have discovered is challenging some of the basic assumptions we have about stem cells.

One of those assumptions is that once a stem cell has been 'fated' for differentiation, there's no going back. "In fact, it appears that stem cells are much more adaptable than previously thought," said Simons.

By using fluorescent markers and live imaging to track a stem cell's progression, Simons' group has found that they can move backwards and forwards between states biased towards renewal and differentiation, depending on their physical position in the their host environment, known as the stem cell niche.

For example, some have argued that mammals, from elephants to mice, require just a few hundred blood stem cells to maintain sufficient levels of blood in the body. "Which sounds crazy," said Simons. "But if the self-renewal potential of cells may vary reversibly, the number of cells that retain stem cell potential may be much higher. Just because a certain cell may have a low chance of self-renewal today doesn't mean that it will still be low tomorrow or next week!"

Chalut's group is also looking at the way in which stem cells interact with their environment, specifically at the role that their physical and mechanical properties might play in how they make their fate decisions. It's a little-studied area, but one that could play a key role in understanding how stem cells work.

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Stem cell researchers at Harvard University have devised a method for creating large quantities of human insulin-producing beta cells, which could soon lead to a cure for type 1 diabetes as well as a new treatment for type 2 diabetes. The cells are currently being trialled in animals and non-human primates with hopes human trials could take place in the near future..

The researchers built a three-dimensional cell culture system using 500 ml spinner flasks containing undifferentiated human pluripotent stem cells. The flasks were placed on a magnetic stirrer and the cells were fed special proteins over a 33-day period. After further treatment and imaging, the insulin-secreting stem-cell-derived- cells were transplanted into diabetic mice, which had a higher survival rate and lower blood glucose level than the control group under three different scenarios.

The cells produced were found to mimic the function of human islets (clusters of cells scattered throughout the pancreas), which are crucial in regulating blood sugar. Type 1 diabetics lack the beta cells that monitor blood sugar levels and release insulin to normalize it because their immune system attacks and destroys these cells. Transplanted beta cells grown in a lab may provide a long-term solution, but until now they could not be grown in sufficient quantities to treat the disease.

The other remaining piece in the diabetes cure puzzle involves pinpointing a method for protecting the transplanted cells around 150 million of them in each patient from immune system attack (otherwise patients would require repeated and regular or semi-regular transplantations). Lead researcher Doug Melton is collaborating with Daniel G. Anderson of the Koch Institute at MIT on an implantation device that has thus far protected beta cells implanted in mice for many months.

Anderson described the work of Melton's lab as "an incredibly important advance for diabetes" as it "opens the doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy."

Type 1 diabetes affects an estimated three million Americans, who for the most part must currently regulate their blood sugar levels by injecting insulin multiple times a day. But without the kind of fine-tuned metabolic control that glucose-sensing, insulin-secreting beta cells can provide, they face potential complications as severe as blindness and loss of limbs. Transplanted beta cells could also help type 2 diabetics who are dependent on insulin injections.

"We are now just one pre-clinical step away from the finish line," said Melton, who hopes to see transplantation trials in humans begin in the next few years.

A paper describing the research was published in the journal Cell.

Source: Harvard University

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Scientists close in on diabetes cure with production of insulin-producing cells

People with autism spectrum disorder often experience a period of accelerated brain growth after birth. No one knows why, or whether the change is linked to any specific behavioral changes.

A new study by UCLA researchers demonstrates how, in pregnant mice, inflammation, a first line defense of the immune system, can trigger an excessive division of neural stem cells that can cause "overgrowth" in the offspring's brain.

The paper appears Oct. 9 in the online edition of the journal Stem Cell Reports.

"We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals," said Dr. Harley Kornblum, the paper's senior author and a director of the Neural Stem Cell Research Center at UCLA's Semel Institute for Neuroscience and Human Behavior.

In the study, the researchers mimicked environmental factors that could activate the immune system -- such as an infection or an autoimmune disorder -- by injecting a pregnant mouse with a very low dose of lipopolysaccharide, a toxin found in E. coli bacteria. The researchers discovered the toxin caused an excessive production of neural stem cells and enlarged the offspring's' brains.

Neural stem cells become the major types of cells in the brain, including the neurons that process and transmit information and the glial cells that support and protect them.

Notably, the researchers found that mice with enlarged brains also displayed behaviors like those associated with autism in humans. For example, they were less likely to vocalize when they were separated from their mother as pups, were less likely to show interest in interacting with other mice, showed increased levels of anxiety and were more likely to engage in repetitive behaviors like excessive grooming.

Kornblum, who also is a professor of psychiatry, pharmacology and pediatrics at the David Geffen School of Medicine at UCLA, said there are many environmental factors that can activate a pregnant woman's immune system.

"Although it's known that maternal inflammation is a risk factor for some neurodevelopmental disorders such as autism, it's not thought to directly cause them," he said. He noted that autism is clearly a highly heritable disorder, but other, non-genetic factors clearly play a role.

The researchers also found evidence that the brain growth triggered by the immune reaction was even greater in mice with a specific genetic mutation -- a lack of one copy of a tumor suppressor gene called phosphatase and tensin homolog, or PTEN. The PTEN protein normally helps prevent cells from growing and dividing too rapidly. In humans, having an abnormal version of the PTEN gene leads to very large head size or macrocephaly, a condition that also is associated with a high risk for autism.

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Neural stem cell overgrowth, autism-like behavior linked, mice study suggests

Chuck Bednar for redOrbit.com Your Universe Online

Researchers writing in the October 9 edition of the journal Cell report they have for the first time successfully converted human embryonic stem cells into insulin-producing beta cells equivalent in nearly every way to regular, normally-functioning beta cells.

The discovery, which was the work of a team led by Douglas Melton of the Harvard University Department of Stem Cell and Regenerative Biology and the Howard Hughes Medical Institute, is being hailed as a breakthrough in the search for an effective way to treat type 1 diabetes a disease which affects an estimated three million Americans each year.

According to BBC News online health editor James Gallagher, Melton and his colleagues were able to produce hundreds of millions of the cells in their laboratory. Furthermore, their tests on mice demonstrated that the cells could treat the disease, which is caused when the immune system begins destroying the cells that are responsible for controlling blood glucose levels.

Beta cells in the pancreas pump out insulin to bring down blood sugar levels, Gallagher said. But the bodys own immune system can turn against the beta cells, destroying them and leaving people with a potentially fatal disease because they cannot regulate their blood sugar levels. It is different to the far more common type 2 diabetes.

Melton, who started his search for a cure for type 1 diabetes when his infant son Sam was diagnosed with the disease 23 years ago, said that he hopes to start human transplantation trials using the cells within a few years time. The professor, whose daughter also has type 1 diabetes, said in a statement that his team is now just one preclinical step away from the finish line.

The breakthrough comes after 15 years of seeking a bulk recipe for making beta cells, which sense the level of sugar in the blood and keep it in a healthy range by making precise amounts of insulin, said John Lauerman of Bloomberg Businessweek. He added that the technique, which begins with human stem cells, which have the ability to become any type of tissue or organ, is an important step toward understanding and treating diabetes.

This is part of the holy grail of regenerative medicine or tissue engineering, trying to make an unlimited source of cells or tissues or organs that you can use in a patient to correct a disease, added Albert Hwa, director of discovery science at JDRF, a New York-based type 1 diabetes research group that funded Meltons work.

The Harvard researcher explained to Lauerman that their research has led to the development of a six-step recipe for making mature, insulin-secreting beta cells that takes 30 days. He added that laboratories will be able to use the cells to test drugs to treat type 1 diabetes, as well as to gain new insight as to how the disease originally occurs.

In addition, since the researchers successfully manufactured the millions of beta cells required for transplantation, Telegraph Science Editor Sarah Knapton said that it could spell the end of daily insulin injections for the 400,000 type 1 diabetes patients in the UK and the over 30,000 Americans newly diagnosed with the disease each year.

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Stem Cell Breakthrough Brings Researchers One Step Closer To Type 1 Diabetes Cure

CAMBRIDGE, Mass., Oct. 9 (UPI) -- Patients with type 1 diabetes lack the insulin-producing cells that keep blood glucose levels in check. Currently, these patients must use insulin pumps or daily hormone injections to keep levels stable.

But in a recent breakthrough in laboratories at Harvard University, researchers came upon a new technique for transforming stem cells into pancreatic beta cells that respond to glucose levels and produce insulin when necessary. The breakthrough could lead to new less invasive, more hands-off treatment for diabetes.

Remarkably, the new technique -- a complex process which involves turning on and off specific genes and takes about 40 days and six precise steps to complete -- was replicated not only on embryonic stem cells but also on human skin cells reprogrammed to act in a stem-cell-like manner. This revelation allows scientists to produce millions of insulin-producing cells while avoiding the ethical dilemmas attached to traditional stem cell research.

Previous attempts to convert stem cells into insulin-producers have proven moderately successful, but these cells mostly produced insulin at will, unable to adjust their output on the fly. The latest techniques -- developed by Douglas Melton, co-director of the Harvard Stem Cell Institute, and his research colleagues -- produce insulin cells that react to glucose spikes by upping production, and lowering insulin output when there's not excess sugar to break down.

The breakthrough has already shown significant promise when used on lab mice. Diabetic mice who received a transplant of the stem cell beta cells had improved blood sugar levels, and were shown to be capable of breaking down sugar.

"We can cure their diabetes right away -- in less than 10 days," Melton told NPR. "This finding provides a kind of unprecedented cell source that could be used for cell transplantation therapy in diabetes."

But there's still one major issue. For reasons doctors still don't understand, the beta cells in humans with diabetes are attacked by the body's immune system. Researchers like Melton still have to figure out a way to protect the new beta cells from being killed -- otherwise the breakthrough won't become anything more than another short-term solution.

"It's taken me 10 to 15 years to get to this point, and I consider this a major step forward," Melton told TIME. "But the longer term plan includes finding ways to protect these cells, and we haven't solved that problem yet."

2014 United Press International, Inc. All Rights Reserved. Any reproduction, republication, redistribution and/or modification of any UPI content is expressly prohibited without UPI's prior written consent.

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Harvard researchers grow insulin-producing stem cells

Harvard scientists made insulin-producing beta cells from human stem cells. After transplantation into mice with diabetes, the lab-made beta cells produced enough insulin to cure the animals. Harvard University hide caption

Harvard scientists made insulin-producing beta cells from human stem cells. After transplantation into mice with diabetes, the lab-made beta cells produced enough insulin to cure the animals.

A team of Harvard scientists said Thursday that they had finally found a way to turn human embryonic stem cells into cells that produce insulin. The long-sought advance could eventually lead to new ways to help millions of people with diabetes.

Right now, many people with diabetes have to regularly check the level of sugar in their blood and inject themselves with insulin to keep the sugar in their blood in check. It's an imperfect treatment.

"This is kind of a life-support for diabetics," says Doug Melton, a stem-cell researcher at Harvard Medical School. "It doesn't cure the disease and leads to devastating complications of the disease."

People with poorly controlled diabetes can suffer complications such as blindness, amputations and heart attacks.

Researchers have had some success transplanting insulin-producing cells from cadavers into people with diabetes. But it's been difficult to procure enough cells to treat large numbers of patients. So scientists have been trying to figure out how they could get more cells more easily.

For Melton, who led the work at Harvard, this has been a personal quest. His son, Sam, was diagnosed with Type 1 diabetes when he was 6 months old, and his daughter, Emma, was diagnosed with the disease when she was 14.

"I do what any parent would do, which is to say, 'I'm not going to put up with this, and I want to find a better way,' " he says.

And now Melton and his colleagues are reporting in a paper being published in this week's issue of the journal Cell that they think they have finally found that better way.

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Scientists Coax Human Embryonic Stem Cells Into Making Insulin

TIME Health medicine Type 1 Diabetes Treatment Gets Boost from Stem Cells Insulin-making cells grown from stem cells glow green two weeks after they are transplanted into mice (c) Douglas Melton 2014 Scientists started with stem cells and created the first insulin-making cells that respond to changes in glucose

Scientists are closer to a potential stem cell treatment for type 1 diabetes.

In a new article in the journal Cell, Douglas Melton, co-director of the Harvard Stem Cell Institute (and one of the 2009 TIME 100) and his colleagues describe how they made the first set of pancreatic cells that can sense and respond to changing levels of sugar in the blood and churn out the proper amounts of insulin.

Its a critical first step toward a more permanent therapy for type 1 diabetics, who currently have to rely on insulin pumps that infuse insulin when needed or repeated injections of the hormone in order to keep their blood sugar levels under control. Because these patients have pancreatic beta cells that dont make enough insulin, they need outside sources of the hormone to break down the sugars they eat.

MORE: Stem-Cell Research: The Quest Resumes

Melton started with two types of stem cells: those that come from excess embryos from IVF procedures, and those that can be made from skin or other cells of adults. The latter cells, known as iPS cells, have to be manipulated to erase their developmental history and returned back to an embryonic state. They then can turn into any cell in the body, including the pancreatic beta cells that produce insulin. While the embryonic stem cells from IVF dont require this step, they arent genetically matched to patients, so any beta cells made from them may cause immune reactions when they are transplanted into diabetic patients.

Both techniques, however, produced similar amounts of insulin-making beta cellssomething that would have surprised Melton a few years ago. But advances in stem cell technology have made even the iPS cells pretty amenable to reprogramming into beta cells. Meltons group tested more than 150 different combinations of more than 70 different compounds, including growth factors, hormones and other signaling proteins that direct cells to develop into specific cell types, and narrowed the field down to 11 factors that efficiently turned the stem cells into functioning beta cells.

MORE: Woman Receives First Stem Cell Therapy Using Her Own Skin Cells

The two populations of stem cells churned out hundreds of millions of insulin-making cells, which is the volume of cells that a patient with type 1 diabetes would need to cure them and free them from their dependence on insulin. An average patient, says Melton, would need one or two large coffee cups worth of cells, each containing about 300 million cells. Melton and his team then conducted a series of tests in a lab dish to confirm that the cells were functioning just like normal beta cells by producing more insulin when they were doused with glucose, and less when glucose levels dropped. That was a huge advance over previous efforts to make beta cells from stem cellsthose cells could produce insulin, but they didnt respond to changing levels of glucose and continuously pumped out insulin at will.

Next, the scientists transplanted about five million of the stem cell derived beta cells into healthy mice, and two weeks later, gave them an injection of glucose. About 73% of the mice produced enough insulin to successfully break down the sugar. Whats more, that was similar to the proportion of mice responding to glucose after getting a transplant of beta cells from human cadavers. That was especially encouraging since some type 1 diabetics currently receive such transplants to keep their diabetes under control. Weve now shown that we can produce an inexhaustible source of beta cells without having to do to cadavers, he says.

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Type 1 Diabetes Treatment Gets Boost from Stem Cells

October 8, 2014

Image Caption: New genetic barcoding technology allows scientists to identify differences in origin between individual blood cells. Credit: Camargo Lab

Provided by Joseph Caputo, Harvard University

New technology that tracks the origin of blood cells challenges scientific dogma

A 7-year-project to develop a barcoding and tracking system for tissue stem cells has revealed previously unrecognized features of normal blood production: New data from Harvard Stem Cell Institute scientists at Boston Childrens Hospital suggests, surprisingly, that the billions of blood cells that we produce each day are made not by blood stem cells, but rather their less pluripotent descendants, called progenitor cells. The researchers hypothesize that blood comes from stable populations of different long-lived progenitor cells that are responsible for giving rise to specific blood cell types, while blood stem cells likely act as essential reserves.

The work, supported by a National Institutes of Health Directors New Innovator Award and published in Nature, suggests that progenitor cells could potentially be just as valuable as blood stem cells for blood regeneration therapies.

This new research challenges what textbooks have long read: That blood stem cells maintain the day-to-day renewal of blood, a conclusion drawn from their importance in re-establishing blood cell populations after bone marrow transplantsa fact that still remains true. But because of a lack of tools to study how blood forms in a normal context, nobody had been able to track the origin of blood cells without doing a transplant.

Boston Childrens Hospital scientist Fernando Camargo, PhD, and his postdoctoral fellow Jianlong Sun, PhD, addressed this problem with a tool that generates a unique barcode in the DNA of all blood stem cells and their progenitor cells in a mouse. When a tagged cell divides, all of its descendant cells possess the same barcode. This biological inventory system makes it possible to determine the number of stem cells/progenitors being used to make blood and how long they live, as well as answer fundamental questions about where individual blood cells come from.

Theres never been such a robust experimental method that could allow people to look at lineage relationships between mature cell types in the body without doing transplantation, Sun said. One of the major directions we can now go is to revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system.

People have tried using viruses to tag blood cells in the past, but the cells needed to be taken out of the body, infected, and re-transplanted, which raised a number of issues, said Camargo, who is a member of Childrens Stem Cell Program and an associate professor in Harvard Universitys Department of Stem Cell and Regenerative Biology. I wanted to figure out a way to label blood cells inside of the body, and the best idea I had was to use mobile genetic elements called transposons.

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Scientists Develop Barcoding Tool For Stem Cells

When his infant son Sam was diagnosed with type 1 diabetes two decades ago, Doug Melton made himself a promise: He would cure it. When his daughter Emma was diagnosed with the same autoimmune disease at 14, he redoubled his efforts.

Finally he can see the finish line. In a paper published Thursday in the journal Cell, Melton announces that he has created a virtually unlimited supply of the cells that are missing in people with type 1 diabetes.

By replacing these cellsand then protecting them from attack by the body's immune systemMelton, now a professor and stem cell researcher at Harvard, says someday he'll have his cure.

"I think we've shown the problem can be solved," he said.

In type 1 diabetes, which usually starts in childhood and affects as many as three million Americans, the person's immune system attacks and destroys beta cells in the pancreas. Melton used stem cellswhich can turn into a wide variety of other cell typesto manufacture a new supply of these beta cells, which provide exquisitely fine-tuned responses to sugar levels in the blood.

When you eat, beta cells increase levels of insulin in your blood to process the extra sugar; when you're running on empty, the cells dial down insulin levels.

Since the 1920s, people with type 1 diabetes have been kept alive with insulin injections, though many still face nerve damage, slow wound healing, and even blindness because even the best pumps and monitors are not as effective as the body's beta cells.

The only known cure for type 1 diabetes is a beta cell transplant, which takes the cells from someone who has recently died. But the procedure is complicated, and the patient must remain on drugs forever to prevent the immune system from destroying the cells.

Fewer than 1,000 beta cell transplants have ever been done, said Albert Hwa, senior scientific program manager for beta cell therapies at the Juvenile Diabetes Research Foundation, which has helped fund Melton's work for more than a decade.

Hope From Stem Cells

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New Stem Cell Treatment, Successful in Mice, May Someday Cure Type 1 D

Henderson, NV (PRWEB) October 07, 2014

Stem cells from plants are becoming an increasingly popular way to turn the clock backward on skin aging. Hylunia's own light and silky Moisure Infusion contains plant stem cells and peptides that are thought to delay aging, making skin look softer smoother and younger.

Plant stem cells like the ones found in grapes are undifferentiated cells from the meristems of plants. Like human stem cells, they can replace damaged cells and renew themselves. Plant stem cells are cultured in labs, allowing scientists to have more control over the quality, quantity and purity of a plant's anti-aging substance.

Skin care stem cells are extracted from various plants, including tiny white Edelweiss flowers, a swamp plant called gotu kola, swiss apples, and raspberry cell cultures. Lilac and algae may also be used. Most of these products contain antioxidants and other chemicals that make skin look younger.

Hylunia's unique product features grape stem cells cultivated from the Gamay Teinturier Fraux grape from Burgundy, France. Their ingredient list explains that these grapes are "high in powerful antioxidants and [have] free radical scavenging capabilities."

The site adds that "The Grape Stem Cells contain special epigenetic factors and metabolites which are able to protect human stem cells against UV radiation and therefore delay aging." UV damage is responsible for up to 80% of skin aging.

Hylunia Moisture Infusion also contains peptides, which can boost collagen and block the neurotransmitters that contract the muscles that form wrinkles. They stimulate epidermal skin cells and increase skin healing and repair.

Hyluna's product contains Palmitoyl Trypeptide-5 (patented), which stimulates collagen synthesis to "strengthen skin and reduce the appearance of fine lines and wrinkles."

Hylunia is currently putting together a webinar about plant peptides for their professional customers like spa and salon owners. The webinar will be available soon.

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Hylunia Educates Professional Customers on Anti-Aging Peptides and Stem Cells