PUBLIC RELEASE DATE:

30-Jan-2014

Contact: Bill Hathaway william.hathaway@yale.edu 203-432-1322 Yale University

A fundamental axiom of biology used to be that cell fate is a one-way street once a cell commits to becoming muscle, skin, or blood it always remains muscle, skin, or blood cell. That belief was upended in the past decade when a Japanese scientist introduced four simple factors into skin cells and returned them to an embryonic-like state, capable of becoming almost any cell type in the body.

Hopeful of revolutionary medical therapies using a patient's own cells, scientists rushed to capitalize on the discovery by 2012 Nobel Laureate Shinya Yamanaka. However, the process has remained slow and inefficient, and scientists have had a difficult time discovering a genetic explanation of why this should be.

In the Jan. 30 issue of the journal Cell, Yale School of Medicine researchers identified a major obstacle to converting cells back to their youthful state the speed of the cell cycle, or the time required for a cell to divide.

When the cell cycle accelerates to a certain speed, the barriers that keep a cell's fate on one path diminish. In such a state, cells are easily persuaded to change their identity and become pluripotent, or capable of becoming multiple cell types

"One analogy may be that when temperature increases to sufficient degrees, even a very hard piece of steel can be malleable so that you can give it a new shape easily," said Shangqin Guo, assistant professor of cell biology at the Yale Stem Cell Center and lead author of the paper. "Once cells are cycling extremely fast, they do not seem to face the same barriers to becoming pluripotent."

Guo's team studied blood-forming cells, which when dividing undergo specific changes in their cell cycle to produce new blood cells. Blood-forming progenitor cells normally produce only new blood cells. However, the introduction of Yamanaka factors sometimes but not always help these blood-forming cells become other types of cells. The new report finds that after this treatment blood-forming cells tend to become pluripotent when the cell cycle is completed in eight hours or less, an unusual speed for adult cells. Cells that cycle more slowly remain blood cells.

"This discovery changes the way people think about how to change cell fate and reveals that a basic 'house-keeping' function of a cell, such as its cell cycle length, can actually have a major impact on switching the fate of a cell," said Haifan Lin, director of the Yale Stem Cell Center.

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Mauro Ferrari, who heads the Institute for Academic Medicine at the Houston Methodist Hospital in Texas, is the Italian government's nominee to chair a committee on the controversial Stamina Foundation.

Top scientists in Italy have called on the health minister Beatrice Lorenzin to reconsider the composition of the new scientific advisory committee she has proposed to assess a controversial stem-cell therapy offered by the Stamina Foundation.

Their move follows a renewed media frenzy around the affair, prompted by statements made to the press and television by the committees proposed president, Mauro Ferrari, shortly after he was nominated on 28 December.

The Stamina therapy, which has not been scientifically proven to be effective in a clinical trial, involves extracting mesenchymal stem cells from bone marrow of a patient, manipulating them and then reinjecting them into the same patients blood or spinal fluid. Stamina, based in Brescia, has already treated more than 80 patients for a wide range of serious diseases.

Stamina's practices have been widely criticized by experts both in Italy and outside, and the first government-appointed scientific committee to rule on Stamina prepared a detailed report describing the Stamina protocol as without a scientific basis, ineffective and dangerous. However, a regional court declared that committee unlawfully biased on 4 December. But after that committee's report was leaked to the press on 20 December (see 'Leaked files slam stem-cell therapy'), many families of patients who claim to have been damaged by the therapy announced that they had brought charges for damages against Stamina and its president Davide Vannoni. Both have denied any wrongdoing.

In response to the court findings, minister Lorenzin nominated Ferrari to chair a new committee. Ferrari, who heads the Institute for Academic Medicine at the Houston Methodist Hospital in Texas, told journalists that he was neither for nor against the Stamina method.

However on the 22 January episode of a widely viewed television show, Le iene, Ferrari said he thought Stamina offered Italy the opportunity to take a world lead in bringing experimental therapies into the clinic. He also referred to Stamina as the first important case for regenerative medicine here in Italy, a statement that has incensed some Italian researchers.

Michele de Luca, a stem-cell biologist from the University of Modena and Reggio Emilia says that Ferrari's assertions were an insult to the many scientists in Italy working on translating stem-cell research into new clinical applications. In particular, De Luca's own group was the first in the world to cure a form of blindness with a stem-cell therapy they developed, he points out.

In a letter dated 26 January, which was seen by Nature, four influential clinical scientists say that they were extremely worried by Ferrari's televised statements. The signatories were Silvio Garattini, head of the Mario Negri Institute for Pharmacological Research in Milan; Giuseppe Remuzzi, head of the Mario Negri Institute in Bergamo; Gianluca Vago, rector of the University of Milan; and Alberto Zangrillo, vice-rector for clinical activities at the University Vita-Salute San Raffaele in Milan.

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(CNN) We run too hard, we fall down, we're sick - all of this puts stress on the cells in our bodies. But in what's being called a breakthrough in regenerative medicine, researchers have found a way to make stem cells by purposely putting mature cells under stress.

Two new studies published Wednesday in the journal Nature describe a method of taking mature cells from mice and turning them into embryonic-like stem cells, which can be coaxed into becoming any other kind of cell possible. One method effectively boils down to this: Put the cells in an acidic environment.

"I think the process we've described mimics Mother Nature," said Dr. Charles Vacanti, director of the laboratory for Tissue Engineering and Regenerative Medicine at Brigham & Women's Hospital in Boston and senior author on one of the studies. "It's a natural process that cells normally respond to."

Both studies represent a new step in the thriving science of stem cell research, which seeks to develop therapies to repair bodily damage and cure disease by being able to insert cells that can grow into whatever tissues or organs are needed. If you take an organ that's functioning at 10 percent of normal and bring it up to 25 percent functionality, that could greatly reduce the likelihood of fatality in that particular disease, Vacanti said.

This method by Vacanti and his colleagues "is truly the simplest, cheapest, fastest method ever achieved for reprogramming [cells]," said Jeff Karp, associate professor of medicine at the Brigham & Women's Hospital and principal faculty member at the Harvard Stem Cell Institute. He was not involved in the study.

Before the technique described in Nature, the leading candidates for creating stem cells artificially were those derived from embryos and stem cells from adult cells that require the insertion of DNA to become reprogrammable.

Stem cells are created the natural way every time an egg that is fertilized begins to divide. During the first four to five days of cell division, so-called pluripotent stem cells develop. They have the ability to turn into any cell in the body. Removing stem cells from the embryo destroys it, which is why this type of research is controversial.

Researchers have also developed a method of producing embryonic-like stem cells by taking a skin cell from a patient, for example, and adding a few bits of foreign DNA to reprogram the skin cell to become like an embryo and produce pluripotent cells, too. However, these cells are usually used for research because researchers do not want to give patients cells with extra DNA.

The new method does not involve the destruction of embryos or inserting new genetic material into cells, Vacanti said. It also avoids the problem of rejection: The body may reject stem cells that came from other people, but this method uses an individual's own mature cells.

"It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell," said Haruko Obokata of the Riken Center for Developmental Biology in Japan in a news conference this week.

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Stem Cell Therapy: Plantar Fasciitis
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BRAIGO with Roman Reed and Shubham Banerjee
Developed by Shubham Banerjee, a 7th grade student from Santa Clara, California. https://plus.google.com/u/0/b/111846984926437553504/111846984926437553504/po...

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PUBLIC RELEASE DATE:

30-Jan-2014

Contact: Cody Mooneyhan cmooneyhan@faseb.org 301-634-7104 Federation of American Societies for Experimental Biology

When it comes to finding cures for heart disease scientists are working to their own beat. That's because they may have finally developed a tissue model for the human heart that can bridge the gap between animal models and human patients. These models exist for other organs, but for the heart, this has been elusive. Specifically, the researchers generated the tissue from human embryonic stem cells with the resulting muscle having significant similarities to human heart muscle. This research was published in the February 2014 issue of The FASEB Journal.

"We hope that our human engineered cardiac tissues will serve as a platform for developing reliable models of the human heart for routine laboratory use," said Kevin D. Costa, Ph.D., a researcher involved in the work from the Cardiovascular Cell and Tissue Engineering Laboratory, Cardiovascular Research Center, Icahn School of Medicine at Mt. Sinai, in New York, NY. "This could help revolutionize cardiology research by improving the ability to efficiently discover, design, develop and deliver new therapies for the treatment of heart disease, and by providing more efficient screening tools to identify and prevent cardiac side effects, ultimately leading to safer and more effective treatments for patients suffering from heart disease."

To make this advance, Costa and colleagues cultured human engineered cardiac tissue, or hECTs, for 7-10 days and they self-assembled into a long thin heart muscle strip that pulled on the end-posts and caused them to bend with each heart beat, effectively exercising the tissue throughout the culture process. These hECTs displayed spontaneous contractile activity in a rhythmic pattern of 70 beats per minute on average, similar to the human heart. They also responded to electrical stimulation. During functional analysis, some of the responses known to occur in the natural adult human heart were also elicited in hECTs through electrical and pharmacological interventions, while some paradoxical responses of hECTs more closely mimicked the immature or newborn human heart. They also found that these human engineered heart tissues were able to incorporate new genetic information carried by adenovirus.

"We've come a long way in our understanding of the human heart," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but we still lack an adequate tissue model which can be used to test promising therapies and model deadly diseases. This advance, if it proves successful over time, will beat anything that's currently available."

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Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the most cited biology journals worldwide according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.

FASEB is composed of 26 societies with more than 115,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

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PHILADELPHIA, Jan. 29 (UPI) -- U.S. researchers say they used epithelial stem cells to regenerate different cell types of human skin and hair follicles that may help those going bald.

Dr. Xiaowei "George" Xu, associate professor of pathology and laboratory medicine and dermatology at the Perelman School of Medicine at University of Pennsylvania, and colleagues at the New Jersey Institute of Technology, said they started with human skin cells called dermal fibroblasts.

By adding three genes, they converted those cells into induced pluripotent stem cells, which have the capability to differentiate into any cell types in the body. They then converted the induced pluripotent stem cells into epithelial stem cells, normally found at the bulge of hair follicles.

Starting with procedures other research teams had previously worked out to convert induced pluripotent stem cells into keratinocytes, Xu's team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the induced pluripotent stem cells to generate large numbers of epithelial stem cells.

The team succeeded in turning more than 25 percent of the induced pluripotent stem cells into epithelial stem cells in 18 days.

Those cells were then purified using the proteins they expressed on their surfaces.

"This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles," Xu said in a statement. "And those cells have many potential applications including wound healing, cosmetics and hair regeneration."

The findings were published in Nature Communications.

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WASHINGTON: In a breakthrough, scientists claim to have successfully transformed human skin cells into hair-follicle-generating stem cells for the first time.

Xiaowei "George" Xu from the Perelman School of Medicine, University of Pennsylvania, and colleagues have found a method for converting adult cells into epithelial stem cells (EpSCs), the first time anyone has achieved this in either humans or mice.

The epithelial stem cells, when implanted into immunocompromised mice, regenerated the different cell types of human skin and hair follicles, and even produced structurally recognizable hair shaft, raising the possibility that they may eventually enable hair regeneration in people.

Xu and his team started with human skin cells called dermal fibroblasts. By adding three genes, they converted those cells into induced pluripotent stem cells (iPSCs), which have the capability to differentiate into any cell types in the body. They then converted the iPS cells into epithelial stem cells, normally found at the bulge of hair follicles.

The team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the iPSCs to generate large numbers of epithelial stem cells.

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BOSTON, Jan. 29 (UPI) -- Scientists have stumbled upon a simple way to create stem cells without embryos -- by bathing healthy adult cells in an acid bath for 30 minutes.

A team of researchers from Boston and Japan were able to transform mature blood cells from mice into the equivalent of stem cells by introducing them to an acidic environment. This is the first time that stem cells have been created without having to introduce outside DNA into the cells.

"The fate of adult cells can be drastically converted by exposing mature cells to an external stress or injury. This finding has the potential to reduce the need to utilize both embryonic stem cells and DNA-manipulated iPS cells," said senior author Charles Vacanti.

The latest development, published in the journal Nature, could be used to create stems cells easily and quickly. Stem cells are known to become other kinds of cells, and have the potential to regenerate injured parts of the body. Embryos are a controversial source of such cells, though more are under study, including Nobel-winning research in 2006 that showed skin cells could be genetically reprogrammed to become stem cells.

The researchers aren't sure how this happens, but have hypothesized that it could be due to hidden cell functions that are triggered by external stimuli.

Researchers are now attempting to use the same method to convert human blood cells and believe that if successful it could be used in not only regenerative treatment but cancer treatment as well.

"If we can work out the mechanisms by which differentiation states are maintained and lost, it could open up a wide range of possibilities for new research and applications using living cells," said first author Haruko Obokata, of the RIKEN Center for Developmental Biology.

[Brigham and Women's Hospital] [RIKEN Center for Developmental Biology] [Nature]

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Mouse cells exposed to an acidic environment turned into embryonic-like "STAP" cells. These were used to generate an entire fetus.

A simple lab treatment can turn ordinary cells from mice into a new kind of stem cell, according to a surprising study that hints at a new way to grow tissue for treating illnesses like diabetes and Parkinsons disease.

Researchers in Boston and Japan exposed spleen cells from newborn mice to an acidic environment. In lab tests, that made the cells act like embryonic stem cells, showing enough versatility to produce the tissues of a mouse embryo, for example.

Cells from skin, muscle, fat and other tissue of newborn mice went through the same change, which could be triggered by exposing cells to any of a variety of stressful situations, researchers said.

Its very simple to do. I think you could do this actually in a college lab, said Dr. Charles Vacanti of Brigham and Womens Hospital in Boston, an author of two papers published online Wednesday by the journal Nature. They can be found here and here.

If it works in humans, the method could improve upon an existing method of generating artificial embryonic stem cells, called induced pluripotent stem cells. These IPS cells can be made from patients, then turned into the needed cells, reducing the possibility of transplant rejection. Pluripotent is a term for cells that act like embryonic stem cells, which can turn into nearly any tissue of the body, except for placental tissues.

In San Diego, scientists led by The Scripps Research Institutes Jeanne Loring propose to treat Parkinsons disease patients with brain cells generated from their own IPS cells. Because these cells arent taken from human embryos, they dont raise the ethical concerns some have with using embryonic stem cells.

However induced pluripotent stem cells are made by reprogramming ordinary cells with added genes or chemicals, which raises concerns about safety. The new method, in contrast, causes the cell to change its own behavior after researchers have applied an external stress. The actual DNA sequence is unaltered, creating a change that is epigenetic, or taking place outside the genome. Researchers dubbed the new cells STAP cells, for stimulus-triggered acquisition of pluripotency.

This is part of a shift in our view of pluripotency, Loring said by email. Eight years ago we thought that cells were stable -- whatever they are, they stay that way. Now, were thinking in terms of how powerful epigenetics is -- that we can change cell fate without changing their DNA.

Loring said it will take years to apply the new method for human therapy.

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EA Regenerative Medicine Center of Excellence
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16 hours ago A Greater mouse-eared bat in Frankfurt, Germany, on January 17, 2014

Europe's bat population recovered by more than 40 percent between 1993 and 2011 after decades of decline, according to a survey published by the European Environment Agency (EEA) on Thursday.

In their most comprehensive study yet, surveyors fanned out across nine countries to count numbers at 6,000 sites used for hibernation by 16 of Europe's 45 bat species.

The bat population increased by 43 percent overall from 1993 to 2011, "with a relatively stable trend since 2003," the Copenhagen-based agency said.

Two species, the whiskered bat (Myotis mystacinus) and Brandt's bat (M. brandtii), showed strong growth, and eight species had moderate gains.

Three species were stable and the picture for two species was unclear. There was a decline in only one species, the grey long-haired bat (Plecotus austriacus).

Bat populations in Europe plummeted in the latter half of the 20th century, their habitat wrecked by intensive agriculture, deliberate destruction of their roosts or use of toxic chemicals to treat timbers in old buildings.

Many of the species with rising populations remain rare and vulnerable, with climate change an emerging threat, the EEA said.

"It is extremely encouraging to see bat populations increasing after massive historic declines," the agency's executive director, Hans Bruyninckx, said.

"It suggests that targeted conservation policies over the last years have been successful. But many bat species are still endangered, so preserving their habitats is still an important priority."

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January 30, 2014

Image Caption: A single gene in honey bees separates the queens from the workers. Credit: Zachary Huang

April Flowers for redOrbit.com Your Universe Online

In a hive of honey bees, the jobs of queen and worker are drastically different. A new study from Michigan State University and Wayne State University reveals, however, that only a single gene separates the two. The findings, published in Biology Letters, show this gene not only determines leg and wing development, but it also plays a crucial role in the evolution of bees ability to carry pollen.

This gene is critical in making the hind legs of workers distinct so they have the physical features necessary to carry pollen, said Zachary Huang, MSU entomologist. Other studies have shed some light on this genes role in this realm, but our team examined in great detail how the modifications take place.

The gene is called Ultrabithorax, or Ubx, and it allows workers to develop a smooth spot on the hind legs where the pollen baskets are located. The gene also promotes the formation of 11 neatly spaced bristles on another part of the legs. This section is known as the pollen comb.

Another part of the hind legs affected by the Ubx gene is known as the pollen press. It is a protrusion that helps pack and transport pollen back to the hive.

Ubx promotes the development of these features on worker bees, but not on the queens. The team confirmed this by isolating and silencing Ubx which made the pollen baskets, specialized leg features used to collect and transport pollen, disappear completely. The team also saw an inhibition of the growth of pollen combs, as well as a reduction in the size of pollen presses.

Bumble bees are in the same family as honey bees, but there are differences. Bumble bee queens, for example, have pollen baskets similar to workers. In bumble bees, Ubx played a similar role in modifying hind legs because the gene is more highly expressed in hind legs than it is in front and mid legs.

There are more than 300 species of bees, other than the honey bee, in Michigan alone including solitary leaf cutter bees, communal sweat bees and social bumble bees.

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Can Animals Do Human Things Better Than Humans?
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Mathematical Models in Population Genetics I
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Newswise Scientists from UCLAs Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have received new awards from the California Institute of Regenerative Medicine (CIRM), the state stem cell research agency, that will forward revolutionary stem cell science in medicine.

Recipients included Dr. Lili Yang, assistant professor of microbiology, immunology and molecular genetics who received $614,400 for her project to develop a novel system for studying how stem cells become rare immune cells; Dr. Denis Evseenko, assistant professor of orthopedic surgery, who received $1,146,468 for his project to identify the elements of the biological niche in which stem cells grow most efficiently into articular cartilage cells; Dr. Thomas Otis, professor and chair of neurobiology and Dr. Ben Novitch, assistant professor of neurobiology, who received $1,148,758 for their project using new light-based optigenetic techniques to study the communication between nerve and muscle cells in spinal muscular atrophy, an inherited degenerative neuromuscular disease in children; and Dr. Samantha Butler, assistant professor of neurobiology, received $598,367 for her project on discovering which molecular elements drive stem cells to become the neurons, or nerve cells, in charge of our sense of touch.

These basic biology grants form the foundation of the revolutionary advances we are seeing in stem cell science, said Dr. Owen Witte, professor and director of the Broad Stem Cell Research Center, and every cellular therapy that reaches patients must begin in the laboratory with ideas and experiments that will lead us to revolutionize medicine and ultimately improve human life. That makes these awards invaluable to our research effort.

The awards were part of CIRMs Basic Biology V grant program, carrying on the initiative to foster cutting-edge research on significant unresolved issues in human stem cell biology. The emphasis of this research is on unravelling the secrets of key mechanisms that determine how stem cells, which can become any cell in the body, differentiate, or decide which cell they become. By learning how these mechanisms work, scientists can then create therapies that drive the stem cells to regenerate or replace damaged or diseased tissue.

Using A New Method to Track Special Immune Cells All the different cells that make up the blood come from hematopoietic or blood stem cells. These include special white blood cells called T cells, which serve as the foot soldiers of the immune system, attacking bacteria, viruses and other invaders that cause diseases.

Among the T cells is a smaller group of cells called invariant natural killer T (iNKT) cells, which have a remarkable capacity to mount immediate and powerful responses to disease when activated, a small special forces unit among the foot soldiers, and are believed to be important to immune system regulation of infections, allergies, cancer and autoimmune diseases such as Type I diabetes and multiple sclerosis.

The iNKT cells develop in small numbers in the blood, usually less than 1 percent of all the blood cells, and can differ greatly in numbers between individuals. Very little is known about how the blood stem cells produce iNKT cells.

Dr. Lili Yangs project will develop a novel model system to genetically program human blood stem cells to become iNKT cells. Dr. Yang and her colleagues will track the differentiation of human blood stem cells into iNKT cells providing a pathway to answer many critical questions about iNKT cell development.

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The revolutionary discovery that any cell can be rewound to a pre-embryonic state remarkably easily could usher in new therapies and cloning techniques

A LITTLE stress is all it took to make new life from old. Adult cells have been given the potential to turn into any type of body tissue just by tweaking their environment. This simple change alone promises to revolutionise stem cell medicine.

Yet New Scientist has also learned that this technique may have already been used to make a clone. "The implication is that you can very easily, from a drop of blood and simple techniques, create a perfect identical twin," says Charles Vacanti at Harvard Medical School, co-leader of the team involved.

Details were still emerging as New Scientist went to press, but the principles of the new technique were outlined in mice in work published this week. The implications are huge, and have far-reaching applications in regenerative medicine, cancer treatment and human cloning.

In the first few days after conception, an embryo consists of a bundle of cells that are pluripotent, which means they can develop into all cell types in the body. These embryonic stem cells have great potential for replacing tissue that is damaged or diseased but, as their use involves destroying an embryo, they have sparked much controversy.

To avoid this, in 2006 Shinya Yamanaka at Kyoto University, Japan, and colleagues worked out how to reprogram adult human cells into what they called induced pluripotent stem cells (iPSCs). They did this by introducing four genes that are normally found in pluripotent cells, using a harmless virus.

The breakthrough was hailed as a milestone of regenerative medicine the ability to produce any cell type without destroying a human embryo. It won Yamanaka and his colleague John Gurdon at the University of Cambridge a Nobel prize in 2012. But turning these stem cells into therapies has been slow because there is a risk that the new genes can switch on others that cause cancer.

Now, Vacanti, along with Haruko Obokata at the Riken Center for Developmental Biology in Kobe, Japan, and colleagues have discovered a different way to rewind adult cells without touching the DNA. The method is striking for its simplicity: all you need to do is place the cells in a stressful situation, such as an acidic environment.

The idea that this might work comes from a phenomenon seen in the plant kingdom, whereby drastic environmental stress can change an ordinary cell into an immature one from which a whole new plant can arise. For example, the presence of a specific hormone has been shown to transform a single adult carrot cell into a new plant. Some adult cells in reptiles and birds are also known to have the ability to do this.

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