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Life or death: Girl in need of stem cell match

Milton Canadian Champion

Anne Hodgkinson and Paul Herron are living every parents worst nightmare. Again.

When their daughter Katie Herron, now four years old, battled cancer as a toddler, the fight for the little girls health was a private, family affair. The youngster endured many months of cancer treatment and battled her way back to a healthy recovery.

That all changed last November.

The Cambridge family doesnt worry about privacy anymore. Theyre now telling everyone they know Katies acute lymphoblastic leukemia is back. Katies life depends on it.

Although the type of cancer that has taken hold of her body usually has a high success rate of responding to treatment, the girl is among the small percentage of children who cant beat the leukemia using standard treatment protocols.

Katies only life-saving option now is to find a stem cell donor match.

Weve got to find a match and weve go to find it soon, explained an emotionally-raw Hodgkinson, as she paced the hallways of Hamiltons McMaster Childrens Hospital, where Katie has lived since the fall.

We have to find a match. She is fighting for her life.

Its hoped a stem cell match would help reboot Katies blood by essentially wiping out her white blood cells and replacing them with a matched transplant of healthy white blood cells. The procedure would enable her body to fight for itself.

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Life or death: Girl in need of stem cell match

Stem cell breakthrough may herald age of personalised medicine

29/01/2014 - 15:56:06Back to World Home

A revolutionary new approach to creating stem cells in the laboratory could open up a new era of personalised medicine, it is claimed.

Scientists have shown it is possible to reprogramme cells into an embryonic-like state simply by altering their environment.

It means in principle that cells can have their developmental clock turned back without directly interfering with their genes something never achieved before.

The cells become pluripotent, having the potential ability to transform themselves into virtually any kind of tissue in the body, from brain to bone.

Reprogramming a patients own cells in this way is seen as the Holy Grail of regenerative medicine, raising the prospect of repairing diseased and damaged organs with new healthy tissue that will not be rejected by the immune system.

Current methods of performing the same trick involve genetic manipulation, which carries with it a serious risk of triggering cancer.

But the new method described in the journal Nature requires no genetic tweaking. Scientists simply bathed immature white blood cells from mice in an acidic solution for 25 minutes.

Tests showed that, stressed in this way, some of the cells lost their blood identity and produced gene markers typical of early embryos.

When these cells were transferred to a special growth-promoting culture medium they began to multiply and acquired features typical of embryonic stem cells.

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Stem cell breakthrough may herald age of personalised medicine

Cell cycle speed is key to making aging cells young again

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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Cell cycle speed is key to making aging cells young again

Stem cell power unleashed after 30 minute dip in acid

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Leader: "Stem cell breakthrough could reopen clone wars"

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.

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Stem cell power unleashed after 30 minute dip in acid

New breakthrough in stem cell research

(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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New breakthrough in stem cell research

Scientists make pure precursor liver and pancreas cells from stem cells

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A new study published in the journal Cell Stem Cell, describes how scientists have developed a way of producing highly sought populations of a pure tissue-specific cell from human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) are precursor cells than can produce over 200 distinct cell types in the human body. They hold great promise for regenerative medicine and drug screening. The idea is to be able to generate a range of pure tissue types by manipulating these precursor cells.

However, it is proving very challenging to obtain large numbers of pure, untainted, tissue-specific cells from hPSCs. Part of the problem is how to ensure they receive highly specific signals, that do not coax them down paths that lead to a range of other tissue types.

Now, a team led by the Genome Institute of Singapore (GIS) in the Agency for Science, Technology and Research (A*STAR) has developed a new way of coaxing hPSCs to produce highly pure populations of endoderm, a valuable cell type that gives rise to organs like the liver and pancreas, bringing closer the day when stem cells can be used in clinical settings.

One of the study leaders is Dr. Bing Lim, senior group leader and associate director of Cancer Stem Cell Biology at the GIS. He and his colleagues developed a highly systematic and novel screening method.

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Scientists make pure precursor liver and pancreas cells from stem cells

Researchers make stem cell discovery by studying tissue stress and repair

GWEN IFILL: Todays news of a breakthrough in stem cell research captured the attention of scientists around the world.

For years, researchers have been investigating how to get adult stem cells to behave more like embryonic ones, which would allow them to be developed into almost any organ or tissue. The findings announced today involve a simple treatment, immersing adult mouse cells in a mild acid bath. As seen here, mouse embryos were grown with beating heart cells derived from this process.

Dr. Charles Vacanti was one of the lead researchers from the team at Brigham and Womens Hospital. And he joins me now.

Dr. Vacanti, this is kind of amazing. Are you explaining are you telling us youre making stem cells, instead of finding them?

DR. CHARLES VACANTI, Brigham & Womens Hospital: That is correct. And we believe were doing exactly whats being done in the body when you normally have an injury.

GWEN IFILL: So how did you come about this?

CHARLES VACANTI: Its been a long process.

I started working with this with my brother Martin about 15 years ago, first looking for a better cell to use in tissue engineering. And in 2001, we described a stem cell that we thought we had found, and several years later, we started to wonder, rather than finding the cell, were we making the cell with the harsh environment of the isolation process?

GWEN IFILL: And thats the acid bath I was just referring to?

CHARLES VACANTI: Yes.

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Researchers make stem cell discovery by studying tissue stress and repair

Stem cell agency’s grants to UCLA help set stage for revolutionary medicine

PUBLIC RELEASE DATE:

29-Jan-2014

Contact: Shaun Mason smason@mednet.ucla.edu 310-206-2805 University of California - Los Angeles

Scientists from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research were today awarded grants totaling more than $3.5 million by California's stem cell agency for their ongoing efforts to advance revolutionary stem cell science in medicine.

Recipients of the awards from the California Institute of Renerative Medicine (CIRM) included Lili Yang ($614,400), who researches how stem cells become rare immune cells; Denis Evseenko ($1,146,468), who is studying the biological niche in which stem cells grow into cartilage; Thomas Otis and Bennet Novitch ($1,148,758), who are using new techniques to study communication between nerve and muscle cells in spinal muscular atrophy; and Samantha Butler ($598,367), who is investigating the molecular elements that drive stem cells to become the neurons 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. "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 are part of CIRM's Basic Biology V grant program, which fosters cutting-edge research on significant unresolved issues in human stem cell biology, with a focus on unravelling the key mechanisms that determine how stem cells decide which cells they will become. By learning how such mechanisms work, scientists can develop therapies that drive stem cells to regenerate or replace damaged or diseased tissue.

Lili Yang: Tracking special immune cells

The various cells that make up human blood all arise from hematopoietic stem cells. These include special white blood cells called T cells, the "foot soldiers" of the immune system that attack bacteria, viruses and other disease-causing invaders. Among these T cells is a smaller group, a kind of "special forces" unit known as invariant natural killer T cells, or iNKT cells, which have a remarkable capacity to mount immediate and powerful responses to disease when activated and are believed to be important to the immune system's 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 generally accounting for less than 1 percent of blood cells but can differ greatly in numbers among individuals. Very little is known about how blood stem cells produce iNKT cells.

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Stem cell agency's grants to UCLA help set stage for revolutionary medicine

Stem Cell Agency Helps Set the Stage for Revolutionary Medicine

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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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Stem Cell Agency Helps Set the Stage for Revolutionary Medicine

Why I’m sure human stem cell trial will be safe

The new kind of stem cell announced yesterday may be the future of regenerative medicine, but Masayo Takahashi's pilot safety study using a type of stem cell to treat age-related blindness is at the cutting edge

Later this year, you will make history when you begin the first ever human trial of induced pluripotent stem cells. Why is this such a big deal? Stem cells have enormous medical potential because they can become any other type of cell. If we can use them to replace old or damaged cells, this could have huge implications for treating degenerative diseases.

Stem cells can be harvested from embryos, but this is ethically controversial. Despite this, there are several trials of these embryonic stem cells under way. Their use often requires drugs to stop the immune system from rejecting them, which can cause complications for elderly patients. Induced pluripotent stem (iPS) cells offer an alternative. These are made from a patient's own cells, removing the need for the immunosuppressant drugs. Plus there are no ethical issues.

How would treatment with iPS cells work? iPS cells are made by injecting several "reprogramming" genes into adult cells that have been removed from the body. This makes them rewind to an embryonic state. Then, we can make iPS cells differentiate into the cell type we need by injecting proteins that instruct embryonic stem cells to become liver, retina or any other type of cell. The idea is that these reprogrammed cells can then be inserted in the body to replace damaged cells. We are at least 20 years from any clinical treatments, but the potential is exciting.

Are there any potential pitfalls with iPS cell treatments? Yes, we have to be very careful because iPS cells multiply endlessly. This means that if any undifferentiated iPS cells were accidentally put into someone, they could cause tumours. That's why this study is so important. It is not a clinical trial, but a six-subject pilot study to confirm the safety of putting cells derived from iPS cells into humans.

Who are the participants in the study? The six people all have age-related macular degeneration in their eyes. This weakens the vision in the central field, eventually leaving people with only peripheral vision. In the type of degeneration we are working with, this is caused by the deterioration of the retinal pigment epithelium (RPE) the layer of cells that clears away extra-cellular debris that lands on the retina.

We aim to replace the damaged section of the RPE with cells created from skin taken from the patient's arm. The skin cells will be reprogrammed into iPS cells and then differentiated into RPE cells. It will take a year to grow enough RPE cells to introduce them to a damaged eye. Although I am excited to see if there is any improvement in sight, this study aims only to demonstrate the safety of RPE cells derived from IPS cells.

How confident are you that the pilot will be a success? Very confident. We have trialled this intervention on mice, rats and monkeys, and observed no tumours. I chose to work with RPE cells because of their characteristic brown pigment. This means we can avoid injecting tumour-causing iPS cells by selecting only the clumps of pure brown RPE cells. Of course, we do have to pick out around 50,000 RPE cells, so it can be a bit tough.

Another reason for optimism is that the retina is the safest place to try this out because we can watch the cells closely through the participant's dilated pupil.

What does the future hold for IPS cells? Right now it takes a lot of time, money and labour to reprogram cells. In our study, each intervention costs 20 million yen ($200,000) per eye and will take 10 people a year to complete. However, my research uses "auto-transplantation", in which the iPS cells come from the patient. The possibility of "allogeneic" treatment, in which iPS cells from one person could be used in many people, could reduce the cost tenfold. Shinya Yamanaka [who won a Nobel prize in 2012 with John Gurdon, for discovering iPS cells] plans to create an iPS cell bank to store a number of genetically average iPS cell cultures those that most easily integrate into people without immuno-rejection.

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Why I'm sure human stem cell trial will be safe