Category Archives: Stem Cells

Scientists have found that reducing the size of tiny hair like structures on stem cells stops them turning into fat. The discovery could be used to develop a way of preventing obesity.

The research, conducted at Queen Mary University of London (QMUL), found that a slight regulation in the length of primary cilia, small hair-like projections found on most cells, prevented the production of fat cells from human stem cells taken from adult bone marrow.

Part of the process by which calories are turned into fat involves adipogenesis, the differentiation of stem cells into fat cells. The researchers showed that during this process of adipogenesis, the length of primary cilia increases associated with movement of specific proteins onto the cilia. Furthermore, by genetically restricting this cilia elongation in stem cells the researchers were able to stop the formation of new fat cells.

Recent research has found that many conditions including kidney disease, blindness, problems with bones and obesity can be caused by defects in primary cilia.

Melis Dalbay, co-author of the research from the School of Engineering and Materials Science at QMUL, said: This is the first time that it has been shown that subtle changes in primary cilia structure can influence the differentiation of stem cell into fat. Since primary cilia length can be influenced by various factors including pharmaceuticals, inflammation and even mechanical forces, this study provides new insight into the regulation of fat cell formation and obesity.

Professor Martin Knight, a bioengineer and lead author of the research, said: This research points towards a new type of treatment known as cilia-therapy where manipulation of primary cilia may be used in future to treat a growing range of conditions including obesity, cancer, inflammation and arthritis.

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The above story is based on materials provided by University of Queen Mary London. Note: Materials may be edited for content and length.

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Changing stem cell structure may help fight obesity

Human neural stem cell treatments are showing promise for reversing learning and memory deficits after chemotherapy, according to UC Irvine researchers.

In preclinical studies using rodents, they found that stem cells transplanted one week after the completion of a series of chemotherapy sessions restored a range of cognitive functions, as measured one month later using a comprehensive platform of behavioral testing. In contrast, rats not treated with stem cells showed significant learning and memory impairment.

The frequent use of chemotherapy to combat multiple cancers can produce severe cognitive dysfunction, often referred to as "chemobrain," which can persist and manifest in many ways long after the end of treatments in as many as 75 percent of survivors -- a problem of particular concern with pediatric patients.

"Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain," said Charles Limoli, a UCI professor of radiation oncology.

Study results appear in the Feb. 15 issue of Cancer Research, a journal of the American Association for Cancer Research.

Many chemotherapeutic agents used to treat disparate cancer types trigger inflammation in the hippocampus, a cerebral region responsible for many cognitive abilities, such as learning and memory. This inflammation can destroy neurons and other cell types in the brain.

Additionally, these toxic compounds damage the connective structure of neurons, called dendrites and axons, and alter the integrity of synapses -- the vital links that permit neurons to pass electrical and chemical signals throughout the brain. Limoli compares the process to a tree being pruned of its branches and leaves.

Consequently, the affected neurons are less able to transmit important neural messages that underpin learning and memory.

"In many instances, people experience severe cognitive impairment that's progressive and debilitating," Limoli said. "For pediatric cancer patients, the results can be particularly devastating, leading to reduced IQ, asocial behavior and diminished quality of life."

For the UCI study, adult neural stem cells were transplanted into the brains of rats after chemotherapy. They migrated throughout the hippocampus, where they survived and differentiated into multiple neural cell types. Additionally, these cells triggered the secretion of neurotrophic growth factors that helped rebuild wounded neurons.

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Human neural stem cells restore cognitive functions impaired by chemotherapy

STEM CELLS (Rise Up) | UpTown Funk Parody - School Project
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In the bone marrow, blood stem cells give rise to a large variety of mature blood cells via progenitor cells at various stages of maturation. Scientists from the German Cancer Research Center (DKFZ) have developed a way to equip mouse blood stem cells with a fluorescent marker that can be switched on from the outside. Using this tool, they were able to observe, for the first time, how stem cells mature into blood cells under normal conditions in a living organism. With these data, they developed a mathematical model of the dynamics of hematopoiesis. The researchers have now reported in the journal Nature that the normal process of blood formation differs from what scientists had previously assumed when using data from stem cell transplantations.

Since ancient times, humankind has been aware of how important blood is to life. Naturalists speculated for thousands of years on the source of the body's blood supply. For several centuries, the liver was believed to be the site where blood forms. In 1868, however, the German pathologist Ernst Neumann discovered immature precursor cells in bone marrow, which turned out to be the actual site of blood cell formation, also known as hematopoiesis. Blood formation was the first process for which scientists formulated and proved the theory that stem cells are the common origin that gives rise to various types of mature cells.

"However, a problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice," says Professor Hans-Reimer Rodewald from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism."

Dr. Katrin Busch from Rodewald's team developed genetically modified mice by introducing a protein into their blood stem cells that sends out a yellow fluorescent signal. This fluorescent marker can be turned on at any time by administering a specific reagent to the animal. Correspondingly, all daughter cells that arise from a cell containing the marker also send out a light signal.

When Busch turned on the marker in adult animals, it became visible that at least one third (approximately 5000 cells) of a mouse's hematopoietic stem cells produce differentiated progenitor cells. "This was the first surprise," says Busch. "Until now, scientists had believed that in the normal state, very few stem cells -- only about ten -- are actively involved in blood formation."

However, it takes a very long time for the fluorescent marker to spread evenly into peripheral blood cells, an amount of time that even exceeds the lifespan of a mouse. Systems biologist Prof. Thomas Hfer and colleagues (also of the DKFZ) performed mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. Their analysis showed that, surprisingly, under normal conditions, the replenishment of blood cells is not accomplished by the stem cells themselves. Instead, they are actually supplied by first progenitor cells that develop during the following differentiation step. These cells are able to regenerate themselves for a long time -- though not quite as long as stem cells do. To make sure that the population of this cell type never runs out, blood stem cells must occasionally produce a couple of new first progenitors.

During embryonic development of mice, however, the situation is different: To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from stem cells.

The investigators were also able to accelerate this process in adult animals by artificially depleting their white blood cells. Under these conditions, blood stem cells increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells. In this process, several hundred times more cells of the so-called myeloid lineage (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells) do.

"When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost," Rodewald explains. "Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception [to the rule]. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism."

The scientists in Rodewald's department, working together with Thomas Hfer, now also plan to use the new model to investigate the impact of pathogenic challenges to blood formation: for example, in cancer, cachexia or infection. This method would also enable them to follow potential aging processes that occur in blood stem cells in detail as they occur naturally in a living organism.

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Observing stem cells maturing into blood cells in living mouse

NEW YORK (Thomson Reuters Foundation) - Human stem cells engineered to produce renewable sources of mature, liver-like cells can be grown and infected with malaria to test potentially life-saving new drugs, according to researchers at the Massachusetts Institute of Technology.

The advance comes at a time when the parasitic mosquito-borne disease, which kills nearly 600,000 people every year, is showing increased resistance to current treatment, especially in Southeast Asia, according to the World Health Organization.

The liver-like cells, or hepatocytes, in the MIT study were manufactured from stem cells derived from donated skin and blood samples.

The resulting cells provide a potentially replenishable platform for testing drugs that target the early stage of malaria, when parasites may linger and multiply in the liver for weeks before spreading into the bloodstream.

Sangeeta Bhatia, a biomedical engineer and senior author of the MIT report, told the Thomson Reuters Foundation that the breakthrough study not only showed that these liver-like cells could host a malaria infection but also described a way to mature the young cells so that an adult-like metabolism, necessary for drug development, could be established.

The study is published in the Feb. 5 online issue of Stem Cell Reports.

Stem cells retain the genetic makeup of their donors, affording researchers the potential to test drugs against a large variety of genetic types and a variety of diseases.

"This allows us to explore in depth how different diseases affect different people, in this case malaria," Bob Palay, chairman and CEO of Cellular Dynamics International (CDI), told the Thomson Reuters Foundation.

"This allows you to study it in a dish and find new drugs," he added, noting that CDI uses blood samples for its stem cells.

Before this development, researchers tested new drugs using human liver cells from cadavers and cancerous liver cells.

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Stem cells offer promising key to new malaria drugs: US research

Stem-cell advocates pin their hopes on an artificial pancreas to treat diabetes.

Fourteen years ago, during the darkest moments of the stem-cell wars pitting American scientists against the White House of George W. Bush, one group of advocates could be counted on to urge research using cells from human embryos: parents of children with type 1 diabetes. Motivated by scientists who told them these cells would lead to amazing cures, they spent millions on TV ads, lobbying, and countless phone calls to Congress.

Now the first test of a type 1 diabetes treatment using stem cells has finally begun. In October, a San Diego man had two pouches of lab-grown pancreas cells, derived from human embryonic stem cells, inserted into his body through incisions in his back. Two other patients have since received the stand-in pancreas, engineered by a small San Diego company called ViaCyte.

Its a significant step, partly because the ViaCyte study is only the third in the United States of any treatment based on embryonic stem cells. These cells, once removed from early-stage human embryos, can be grown in a lab dish and retain the ability to differentiate into any of the cells and tissue types in the body. One other study, since cancelled, treated several patients with spinal-cord injury (see Geron Shuts Down Pioneering Stem-Cell Program and Stem-Cell Gamble), while tests to transplant lab-grown retina cells into the eyes of people going blind are ongoing (see Stem Cells Seem Safe in Treating Eye Disease).

Type 1 diabetes is especially hard on children. If they dont manage their glucose properly, they could suffer nerve and kidney damage, blindness, and a shortened life span.

Type 1 patients must constantly monitor their blood glucose using finger pricks, carefully time when and what they eat, and routinely inject themselves with insulin that the pancreas should make. Insulin, a hormone, triggers the removal of excess glucose from the blood for storage in fat and muscles. In type 1 diabetics, the pancreas doesnt make it because their own immune system has attacked and destroyed the pancreatic islets, the tiny clusters of cells containing the insulin-secreting beta cells.

The routine is especially hard on children, but if they dont manage their glucose properly, they could suffer nerve and kidney damage, blindness, and a shortened life span. Yet despite years of research, there is still just nothing to offer patients, says Robert Henry, a doctor at the University of California, San Diego, whose center is carrying out the surgeries for ViaCyte.

Henry slightly overstates the case, but not by much. There is something called the Edmonton Protocol, a surgical technique first described in the New England Journal of Medicine in 2000. It used islets collected from cadavers; by transplanting them, doctors at the University of Alberta managed to keep all seven of their first patients off insulin for an entire year.

Early hopes for the Edmonton Protocol were quickly tempered, however. Only about half of patients treated have stayed off insulin long-term, and the procedure, which is still regarded as experimental in the U.S., isnt paid for by insurance. It requires recipients to take powerful immune-suppressing drugs for life. Suitable donor pancreases are in extremely short supply.

The early success of the Edmonton Protocol came only two years after the discovery of embryonic stem cells, in 1998. Those pressing for a diabetes cure quickly set a new goal: pair something like the Edmonton Protocol with the technology of lab-grown beta cells, the supplies of which are theoretically infinite.

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A Pancreas in a Capsule

5 hours ago Inside the cell, calcium ions are released from a structure called the endoplasmic reticulum (ER). Forces applied to the bead cause ion channels in the ER to open mechanically (shown in red above), rather through biochemical signaling chemically (shown in green below). Credit: Jie Sun/UC San Diego

After using optical tweezers to squeeze a tiny bead attached to the outside of a human stem cell, researchers now know how mechanical forces can trigger a key signaling pathway in the cells.

The squeeze helps to release calcium ions stored inside the cells and opens up channels in the cell membrane that allow the ions to flow into the cells, according to the study led by University of California, San Diego bioengineer Yingxiao Wang.

Researchers have known that mechanical forces exerted on stem cells have a significant role to play in how the cells produce all kinds of tissuesfrom bone to bloodfrom scratch. But until now, it hasn't been clear how some of these forces translate into the signals that prod the stem cells into building new tissue.

The findings published in the journal eLife could help scientists learn more about "the functional mechanisms behind stem cell differentiation," said Wang, an associate professor of bioengineering. They may also guide researchers as they try to recreate these mechanisms in the lab, to coax stem cells into developing into tissues that could be used in transplants and other therapies.

"The mechanical environment around a stem cell helps govern a stem cell's fate," Wang explained. "Cells surrounded in stiff tissue such as the jaw, for example, have higher amounts of tension applied to them, and they can promote the production of harder tissues such as bone."

Stem cells living in tissue environments with less stiffness and tension, on the other hand, may produce softer material such as fat tissue.

Wang and his colleagues wanted to learn more about how these environmental forces are translated into the signals that stem cells use to differentiate into more specialized cells and tissues. In their experiment, they applied force to human mesenchymal stem cellsthe type of stem cells found in bone marrow that transform into bone, cartilage and fat.

The engineers used a highly focused laser beam to trap and manipulate a tiny bead attached to the cell membrane of a stem cell, creating an optical "tweezers" to apply force to the bead. The squeeze applied by the tweezers was extremely smallon the order of about 200 piconewtons. (Forces are measured in a unit called newtons; one newton is about the weight of an apple held to the Earth by gravity, and one piconewton is equivalent to one-trillionth of a newton.)

When there were no calcium ions circulating outside the cell, this force helped to release calcium ions from a structure inside the cell called the endoplasmic reticulum. The release is aided by the cell's inner structural proteins called the cytoskeleton, along with contracting protein machinery called actomyosin. When the force triggered the movement of calcium ions into the cell from its extracellular environment, only the cytoskeleton was involved, the researchers noted.

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Engineers put the 'squeeze' on human stem cells

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Allogeneic Stem Cell Transplant | Animation Video This video provides extensive details on allogeneic stem cell transplants. A procedure that provides the cancer patient with healthy stem...

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Research scientists (from left) Dr Jim Faed, Vicky Nelson and Dr Paul Turner talk about the possibilities of finding a cure for type 1 diabetes, during the Lion's Lark in the Park at the Dunedin Botanic Garden yesterday. Photo by Gregor Richardson.

Cell biologist, haematologist and project leader Dr Jim Faed, of the University of Otago, made the promise during the Lion's Lark in the Park event at Dunedin's Botanic Garden yesterday, which aimed to help raise some of the $2.46 million needed to run the trials.

Dr Faed said their research involved trials using stem cells taken from the bone marrow of people with type 1 diabetes, and using them to stimulate insulin production.

The cells appeared to be able to ''turn off'' the auto immune response that causes type 1 diabetes, he said.

''We see this as the low hanging fruit of research into a cure for type 1 diabetes because it has already been done once before.''

Trials had already been carried out on mice and humans. It just needed fine tuning, he said.

Much of the funds raised would go towards the Spinal Cord Society which will develop its stem cell production facilities in Dunedin, so that patients' own cells can be grown and tested in clinical trials.

''It's the only method that's attacking the cause of diabetes. Most of the other treatments are basically designed to manufacture insulin artificially.

''What we are looking for is a cure, not just support of people with the disease.

''This will be a sustained cure that doesn't require top ups.''

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Stem cells cure hope for diabetes

STEM CELLS EMBRYOS: ABC Lateline: Alan Trounson David van Gend - 14/8/2002
ABC TV LATELINE "Stem cells: science and ethics clash" - 14/8/2002 TRANSCRIPT at http://www.abc.net.au/lateline/stories/s649062.htm A debate just prior to th...

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STEM CELLS & EMBRYOS: ABC Lateline: Alan Trounson & David van Gend - 14/8/2002 - Video