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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

Are Stem Cells The Cure To Baldness?

January 28, 2014

Brett Smith for redOrbit.com Your Universe Online

While a Chinese cream may not have cured George Costanzas baldness in a classic Seinfeld episode, stem cell research from scientists at the University of Pennsylvania has shown the potential for regenerating hair follicles which could lead to relief for hair-challenged men everywhere.

According to a new report published in the journal Nature Communications, the Pennsylvania researchers have developed a groundbreaking method for converting adult cells into epithelial stem cells (EpSCs). Similar previous efforts have failed to generate an adequate number of hair-follicle-generating stem cells.

In the study, epithelial stem cells were inserted into immunocompromised mice. The stem cells regenerated the various cell types for human skin and hair follicles, and provided structurally identifiable hair shafts, raising the possibility of hair regeneration in humans.

The study team began with human skin cells referred to as dermal fibroblasts. By incorporating three genes, they modified those cells into induced pluripotent stem cells (iPSCs), which have the capacity to differentiate into any cell types in the human body. Next, they modified the iPS cells into epithelial stem cells, commonly located at the base of hair follicles.

Starting with procedures other research groups had worked out to transfer iPSCs into skin cells, Xus team figured out that by carefully manipulating the timing of the cell growth factors, they could drive the iPSCs to produce large quantities of epithelial stem cells. This method was able to turn more than 25 percent of the iPSCs into epithelial stem cells within 18 days. Those cells were then purified based on the proteins they showed on their surfaces.

Comparison of the engineered cells with epithelial stem tissue obtained from hair follicles revealed the team succeeded in making the cells they set out to produce. After mixing all those cells with mouse follicular inductive dermal cells and attaching them onto the pores and skin of immunodeficient mice, the team was able to produce efficient outer layers of human skin tissue and follicles structurally similar to those generated by human hair.

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, said study author Dr. Xiaowei George Xu, associate professor of pathology and laboratory medicine and dermatology at the university. He added that these cells could be used for healing, cosmetics and hair regeneration.

Xu cautioned that iPSC-derived epithelial stem cells are not yet ready for human subjects.

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Are Stem Cells The Cure To Baldness?

Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

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Newswise PHILADELPHIA - If the content of many a situation comedy, not to mention late-night TV advertisements, is to be believed, theres an epidemic of balding men, and an intense desire to fix their follicular deficiencies.

One potential approach to reversing hair loss uses stem cells to regenerate the missing or dying hair follicles. But it hasnt been possible to generate sufficient number of hair-follicle-generating stem cells until now.

Xiaowei George Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine and Dermatology at the Perelman School of Medicine, University of Pennsylvania, and colleagues published in Nature Communications 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, which includes researchers from Penns departments of Dermatology and Biology, as well as the New Jersey Institute of Technology, 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.

Starting with procedures other research teams had previously worked out to convert iPSCs into keratinocytes, Xus 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. In the Xu study, the teams protocol succeeded in turning over 25% of the iPSCs into epithelial stem cells in 18 days. Those cells were then purified using the proteins they expressed on their surfaces.

Comparison of the gene expression patterns of the human iPSC-derived epithelial stem cells with epithelial stem cells obtained from human hair follicles showed that the team had succeeded in producing the cells they set out to make in the first place. When they mixed those cells with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, they produced functional human epidermis (the outermost layers of skin cells) and follicles structurally similar to human hair follicles.

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 says. And those cells have many potential applications, he adds, including wound healing, cosmetics, and hair regeneration.

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Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

Medical breakthrough Cord Blood Center opening in Oklahoma

Posted on: 1:16 pm, January 28, 2014, by Ashley Kringen and KFOR-TV, updated on: 05:37pm, January 28, 2014

Oklahoma City, Okla.-Families at the OU Med Center have the opportunity to help save lives by donating umbilical cord blood, to be used as a source of life for people battling leukemia and other blood disorders.

There are only 24 cord blood centers worldwide and this is the first in Oklahoma.

Dr. James Smith with the Oklahoma Blood Institute said, Were really hoping to be able to meet a very special need.

Each year thousands of people are diagnosed with blood cancers or other blood diseases.

For some, the only hope of a cure is a marrow transplant.

Umbilical cord blood can be used as an alternative to supply those needs.

The goal for Oklahomas Cord Blood Center is to focus on the minority population.

Dr. Smith said Vastly underrepresented in terms of having cord blood or even stem cell donations that are available for transplants.

Mothers would have the option of donating their babys umbilical cord, rather than just throwing it away.

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Medical breakthrough Cord Blood Center opening in Oklahoma

:: 28, Jan 2014 :: SINGAPORE SCIENTISTS SUCCEED IN MANIPULATING STEM CELLS INTO LIVER AND PANCREAS PRECURSOR CELLS

28 January 2014-Scientists from the Genome Institute of Singapore (GIS) in A*STAR have developed a novel method of directing human pluripotent stem cells (hPSCs) into highly pure populations of endoderm[1], a valuable cell type that gives rise to organs including the liver and pancreas.

These cells are highly sought-after for therapeutic and biotechnological purposes, but have been historically difficult to attain from hPSCs. The ability to generate pure endoderm at higher yields from hPSCs is a key and important step towards the use of stem cells in clinical applications.

The discovery, published in the prestigious scientific journal Cell Stem Cell in January 2014, was led by Dr Bing Lim, Senior Group Leader and Associate Director of Cancer Stem Cell Biology at the GIS, Dr Lay Teng Ang, a postdoctoral fellow from Dr Lims lab, and Kyle Loh, a graduate student at Stanford University School of Medicine.

hPSCs are stem cells that can generate over 200 distinct cell types in the human body. They respond to multiple external protein instructions to differentiate into other cell types. Therefore, generating one single cell type from hPSCs, and a pure population of that given cell type, is delicate as hPSCs have a tendency to also form other types of cells.

Employing a highly systematic and novel approach, the group screened for proteins and chemicals that promote the formation of a single desired cell type, and concurrently block induction of unwanted cell types. This strategy uncovered a combination of triggers that could drive hPSCs towards pure populations of endoderm. The valuable cells produced and the insights gained from this work have brought stem cells one step closer to clinical translation and furthered basic research into the understanding of how cell fates are specified during stem cell differentiation.

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:: 28, Jan 2014 :: SINGAPORE SCIENTISTS SUCCEED IN MANIPULATING STEM CELLS INTO LIVER AND PANCREAS PRECURSOR CELLS