Disabled mice regained the ability to walk less than two weeks after receiving human neural stem cells (Photo: Shutterstock)

When scientists at the University of Utah injected human stem cells into mice disabled by a condition similar to multiple sclerosis, they expected the cells to be rejected by the animals' bodies. It turned out that the cells were indeed rejected, but not before they got the mice walking again. The unexpected finding could have major implications for human MS sufferers.

In multiple sclerosis, the body's immune system attacks the myelin sheath that covers and insulates nerve fibers in the spinal cord, brain and optic nerve. With that insulation gone, the nerves short-circuit and malfunction, often compromising the patient's ability to walk among other things.

In the U Utah study (which was begun at the University of California, Irvine) human neural stem cells were grown in a Petri dish, then injected into the afflicted mice. The cells were grown under less crowded conditions than is usual, which reportedly resulted in their being "extremely potent."

As early as one week after being injected, there was no sign of the cells in the animals' bodies evidence that they had been rejected, as was assumed would happen. Within 10 to 14 days, however, the mice were walking and running. After six months, they still hadn't regressed.

This was reportedly due to the fact that the stem cells emitted chemical signals that instructed the rodents' own cells to repair the damaged myelin. Stem cells grown under the same conditions have since been shown to produce similar results, in tests performed by different laboratories.

Additional mouse trials are now planned to assess the safety and durability of the treatment, with hopes for human clinical trials down the road. "We want to try to move as quickly and carefully as possible," said Dr. Tom Lane, who led the study along with Dr. Jeanne Loring from the Center for Regenerative Medicine at The Scripps Research Institute. "I would love to see something that could promote repair and ease the burden that patients with MS have."

A paper on the research was recently published in the journal Stem Cell Reports.

Source: University of Utah

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Human stem cell treatment gets mice with MS-like condition walking again

By Joel Ceausu, May 28th, 2014

An East End Montreal hospital is home to a new national network on regenerative medicine and cell therapy research. CellCAN will be based at Maisonneuve-Rosemont Hospital and directed by renowned cell therapy researcher Dr. Denis Claude Roy. The objective is to unite efforts of researchers, clinicians, funders, industry, charities, government members, patient representatives and the public. Specifically, CellCAN will promote exchanges, cooperation, partnership development and innovation in regenerative medicine and cell therapy, explained Roy. As the hub of a network of cell therapy centers and labs in Toronto, Ottawa, Quebec City, Edmonton, and Vancouver, CellCAN will propel Canadian stem cell research and clinical development forward thanks to a $3 million grant over four years. Discoveries in stem cell research make their way to clinical trials bringing researchers closer to new treatments for patients with cancer, diabetes, cardiovascular and ocular diseases, neurological and blood disorders and other health issues. Regenerative cell therapies have almost unlimited possibilities, said Roy, director of the cellular therapy laboratory at Maisonneuve-Rosemonts research centre. This will transform the nature of medicine and have significant impact on our health care systems. The Universit de Montral-affiliated hospital in Rosemont is an internationally recognized leader in hematology-oncology, stem cell transplants, ophthalmology, nephrology and kidney transplants. The funds come from the federally financed Networks of Centres of Excellence, Maisonneuve-Rosemont Foundation, Ronald and Herbert Black, and various organizations across Canada.n

Click here to see the full newspaper. Updated on May 28, 2014

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Stem cell therapy | biopen Copy
http://www.arthritistreatmentcenter.com I #39;m in Australia again... to report on a fascinating new concept when it comes to stem cells. Surgeons 3D print stem cells and repair bone with biopen...

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By Traci Pedersen Associate News Editor Reviewed by John M. Grohol, Psy.D. on May 25, 2014

Neurons generated from the skin cells of schizophrenia patients behave strangely in the early developmental stages, offering clues that might lead to earlier detection and treatment, according to scientists from the Salk Institute.

The study, published in the journal Molecular Psychiatry, supports the theory that the neurological dysfunction that eventually leads to schizophrenia may begin in the brains of fetuses.

This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia, said Fred H. Gage, Ph.D., professor of genetics at Salk. We were surprised at how early in the developmental process that defects in neural function could be detected.

Up until now, scientists could only study the disease by examining the brains of cadavers; but age, stress, medication, or drug abuse had often changed or damaged these brains, making it harder to figure out the where it all began.

The Salk scientists were able to go around this obstacle by using stem cell technologies. They took skin cells from patients, coaxed the cells back to an earlier stem cell form and then prompted them to grow into very early-stage neurons called neural progenitor cells (NPCs). These NPCs are similar to cells found in the brain of a fetus.

The researchers tested the cells in two ways: In one test, they looked at how far the cells moved and interacted with particular surfaces; in the other test, they looked at cell stress by imaging mitochondria, tiny organelles that generate energy for the cells.

On both tests, the NPCs from schizophrenia patients differed in significant ways from those taken from people without the disease.

In particular, cells taken from people with schizophrenia showed unusual activity in two major classes of proteins: those involved in adhesion and connectivity, and those involved in oxidative stress. Schizophrenia neural cells seemed to have aberrant migration (which may result in the poor connectivity seen later in the brain) and greater levels of oxidative stress.

These results support the current theory that eventsduring pregnancy can contribute to schizophrenia, even though symptoms typically dont begin until early adulthood. For example, previous research suggests that pregnant mothers who experience infection, malnutrition, or extreme stress are at greater risk of having children with schizophrenia.

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Skin Cell Research Suggests Schizophrenia Begins in Womb

The seemingly miraculous recovery of little Hannah Day who rebounded earlier this month after a rare bone marrow transplant cancer free for 60 days has suffered a major setback.

Mother Brooke Ervin said her stem cells, which were transplanted into her daughter on March 19, are attacking her four-year-old daughters body from the inside out, manifesting in a rash and third-degree-like burns.

She has burns to 90 per cent of her body and is now admitted back to [B.C. Childrens] hospital in hopes they can stop it.

Hannah is in immeasurable pain as her family watches, terrified and helpless, Ervin said Wednesday.

Hannah is not responding to oral antibiotics, and steroids being pumped into her body to stop the burning are suppressing her immune system, which is needed to fight off the cancer.

This is such a horrible life she got, a distraught Ervin said.

She has spent most of her life suffering just to stay alive. No one should have to fight so hard, especially an innocent child.

She wants to live so bad and she shows us every day with her fight and will to live, Ervin said. She wont give up and we cant either. We have to hold strong in the hopes one day this will end.

On May 6, Hannah was discharged from hospital in Vancouver after receiving stem cells from her mother in a haploidentical transplant.

Although only a half match, doctors hope Hannahs cells will recognize her moms cells which once protected her in the womb and allow them to kill off cancer cells in Hannahs body.

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After cancer rebound, Victoria's little Hannah Day back into life of pain as transplanted stem cells attack her body

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Newswise SALT LAKE CITY In the body, a skin cell will always be skin, and a heart cell will always be heart. But in the first hours of life, cells in the nascent embryo become totipotent: they have the incredible flexibility to mature into skin, heart, gut, or any type of cell.

It was long assumed that the joining of egg and sperm launched a dramatic change in how and which genes were expressed. Instead, new research shows that totipotency is a step-wise process, manifesting as early as in precursors to sperm, called adult germline stem cells (AGSCs), which reside in the testes.

The study was co-led by Bradley Cairns, Ph.D., University of Utah professor of oncological sciences, and Huntsman Cancer Institute investigator, and Ernesto Guccione, Ph.D., of the Agency for Science Technology and Research in Singapore. They worked closely with first author and Huntsman Cancer Institute postdoctoral fellow, Saher Sue Hammond, Ph.D. The research was published online in the journal Cell Stem Cell.

Typically, sperm precursors live a mundane life. They divide, making more cells like themselves, until they receive the signal instructing them to mature into sperm.

There is evidence, however, that these cells have the potential to do more. Under the unusual conditions that promote the cells to form dense cancerous masses called testicular teratomas, the young sperm transform into precursors of skin, muscle, and gut.

This realization prompted the investigators to examine the gene program within sperm precursors. They wondered, would it be like that of a cell that is destined to become a single cell type, or like that of a cell with the potential to become anything?

The answer, they found, is that the sperm precursors are somewhere in between. The most telling evidence is the status of a quartet of genes: Lefty, Sox2, Nanog, and Prdm14. When activated, the genes can trigger a cascade of events that give cells stem cell properties. In cells limited to becoming one cell type, the genes are silent.

Yet in sperm precursors, the genes bear a code of chemical tags, called methylation groups, indicating that the four genes are silenced, but poised to become active. In other words, embedded within these cells, is the potential to become totipotent.

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The Young Sperm, Poised for Greatness

Stem Cell Therapy Saves Eyesight Of Fountain Valley Mother
Stem cell therapy saved the eyesight of a Fountain Valley mother. CBS2 #39;s Lisa Sigell reports. Official Site: http://losangeles.cbslocal.com/ YouTube: http://...

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Content by UTS

UTS researchers are experimenting with spinal cord tissue.

It all started at a symposium five years ago. Catherine Gorrie, an expert in spinal cord injury, was listening to a presentation about the differences between the developing brains of children and the mature ones of adults when she had an aah-haa moment.

I began to wonder if there is something in the spines of children that could be manipulated for repair, says Dr Gorrie, a neuroscientist at the University of Technology, Sydney (UTS). It made sense. Dr Gorrie already knew that the more adaptable, or plastic, spinal cords of infants responded more efficiently to injury than did those of adults.

If she could tease out the factors that encouraged generic cells, so-called stem cells, in the spines of newborns to become new nerve cells, neurones, Dr Gorrie reasoned that it should be possible to mimic the process and help repair spinal cord injuries in people of all ages. That would be incredibly important because, to date, there is no cure for spinal cord injury and no proven drug treatment.

The most effective treatments available involve the surgical stabilisation of the spinal column and extensive physical therapy to provide some functional improvement, Dr Gorrie says. There is nothing else.

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In Australia, about 10,000 people live with spinal cord injury and 300-400 new cases emerge every year. Most injuries are a result of car accidents, sporting activities or severe falls.

Childhood spinal cord injury is frequently the result of tumours that compress the spine, crushing neurones which transmit signals to and from the brain.

As the notion of exploiting the biomechanical properties of infant spinal cords took shape in her mind, Dr Gorrie pulled together a team of UTS researchers: Dr Matt Padula, Dr Hui Chen and doctoral students Thomas Cawsey and Yilin Mao.

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Knee arthritis/torn meniscus 6 months after stem cell therapy by Dr Harry Adelson
Alan discusses his results six months after stem cell therapy by Dr Harry Adelson for treatment of his arthritic knees and torn menisci http://www.docereclinics.com.

By: Harry Adelson, N.D.

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20 hours ago A signal from Transit-Amplifying Cells (TACs) activates stem cells in the hair follicle, researchers have found. Both types of cells appear in green (top), with TACs clustered lower down. The researchers identified the signal as Sonic Hedgehog. In experiments, such as this one (bottom), they disabled the signal, interfering with hair growth and regeneration.

(Phys.org) Stem cells switch off and on, sometimes dividing to produce progeny cells and sometimes resting. But scientists don't fully understand what causes the cells to toggle between active and quiet states.

New research in Elaine Fuchs' Laboratory of Mammalian Cell Biology and Development focused on stem cells in the hair follicle to determine what switches them on. The researchers found cells produced by the stem cells, progeny known at Transit-Amplifying Cells or TACs, emit a signal that tells quiet hair follicle stem cells to become active.

"Many types of mammalian stem cells produce TACs, which act as an intermediate between the stem cells and their final product: fully differentiated cells in blood, skin and elsewhere," says Ya-Chieh Hsu, who conducted the research while as a postdoc in the lab and will soon move to Harvard University. "In the past, TACs were seen as a population of cells that sat by passively cranking out tissues. No one expected them to play a regulatory role."

Hsu and Fuchs went a step further to identify the signal sent out by the TACs. They pinpointed a cell-division promoting protein called Sonic Hedgehog, which plays a role in the embryonic development of the brain, eyes and limbs.

Stem cells are medically valuable because they have the potential to produce a number of specialized cells suitable for specific roles. Stem cells' production of these differentiated cells is crucial to normal maintenance, growth and repair. Many tissues have two populations of stem cells: one that divides rarely, known as the quiescent stem cells, and another that is more prone to proliferate, known as primed stem cells. Regardless of their proliferation frequency, most stem cells in humans do not directly produce differentiated progeny cells; instead, they give rise to an intermediate proliferating population, the TACs.

The hair follicle, the tiny organ that produces a hair, forms a narrow cavity down into the skin. It cycles between rounds of growth, destruction and rest. When entering the growth phase, the primed stem cell population is always the first to divide and generates the TACs clustered lower down in the hair follicle. Primed stem cell proliferation sets the stage for the next round of hair growth, a process which ensures hairs are replaced as they are lost over time. Proliferating TACs produce the hair shaft, as well as all the cells surrounding the hair underneath the skin, which make up the follicle itself.

At the outset, Hsu and Fuchs suspected a role for both the TACs and for Sonic Hedgehog in hair regeneration.

"We noticed that the primed stem cell population gets activated early and makes the TACs, while the quiescent stem cell population only becomes activated once TACs are generated. This correlation prompted us to look for a signal that is made by the TACs. Sonic Hedgehog is that signal, as we went on to demonstrate," explained Fuchs.

In experiments described this week in Cell, Hsu disabled TACs' ability to produce the Sonic Hedgehog protein by knocking out the gene responsible in the hair follicles of adult mice. As a result, the proliferation of hair follicle stem cells and their TACs are both compromised. They further showed that it is the quiescent stem cell population which requires Sonic Hedgehog directly for proliferation.

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Stem cell progeny tell their parents when to turn on

Man believed to be offering stem-cell therapy without a license
Undercover agents arrested a man claiming to be a doctor who was providing stem-cell treatments for injured athletes. Authorities say the man has no medical professional licenses.

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The entire heart muscle in young children may hold untapped potential for regeneration, new research suggests.

For decades, scientists believed that after a child's first few days of life, cardiac muscle cells did not divide. Instead, the assumption was that the heart could only grow by having the muscle cells become larger.

Cracks were already appearing in that theory. But new findings in mice, scheduled for publication in Cell, provide a dramatic counterexample -- with implications for the treatment of congenital heart disorders in humans.

Researchers at Emory University School of Medicine have discovered that in young mice 15 days old, cardiac muscle cells undergo a precisely timed spurt of cell division lasting around a day. The total number of cardiac muscle cells increases by about 40 percent during this time, when the rest of the body is growing rapidly. [A 15-day-old mouse is roughly comparable to a child in kindergarten; puberty occurs at day 30-35 in mice.]

The burst of cell division is driven by a surge of thyroid hormone, the researchers found. This suggests that thyroid hormone could aid in the treatment of children with congenital heart defects. In fact, doctors have already tested thyroid hormone supplementation in this setting on a small scale.

The findings also have broader hints for researchers developing therapies for the heart. Activating the regenerative potential of the muscle cells themselves is a strategy that is an alternative to focusing on the heart's stem cells, says senior author Ahsan Husain, PhD, professor of medicine (cardiology) at Emory University School of Medicine.

"It's not as dramatic as in fish or amphibians, but we can show that in young mice, the entire heart is capable of regeneration, not just the stem cells," he says.

The Emory researchers collaborated with Robert Graham, MD, executive director of the Victor Change Cardiac Research Institute in Australia. Co-first authors of the paper are Nawazish Naqvi, PhD, assistant professor of medicine at Emory and Ming Li, PhD, at Victor Chang.

The researchers tested how much mice, at the age of day 15, can recover from the blockage of a coronary artery. Consistent with previous research, newborn (day 2) mice showed a high level of repair after such an injury, but at day 21, they did not. The day 15 mice recovered more than the day 21 mice, indicating that some repair is still possible at day 15.

The discovery came unexpectedly during the course of Naqvi and Husain's investigation of the role of the gene c-kit -- an important marker for stem cells -- in cardiac muscle growth. Adult mice with a disabled c-kit gene in the heart have more cardiac muscle cells. The researchers wanted to know: when does this difference appear?

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Spurt of heart muscle cell division seen in mice well after birth: Implications for repair of congenital heart defects

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Newswise Two new gifts from The Eli and Edythe Broad Foundation to UCLA totaling $4 million will fund research in stem cell science and digestive diseases and support the recruitment of key faculty at two renowned research centers.

The gifts bring to $30 million The Broad Foundation's total support of faculty recruitment and basic and translational research at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and at the Center for Inflammatory Bowel Diseases at UCLA's Division of Digestive Diseases.

A $2 million gift to the Broad Stem Cell Research Center adds to The Broad Foundation's original 2007 gift of $20 million, which has supported faculty and research and launched the Innovation Award program, which furthers cutting-edge research at the center by giving UCLA stem cell scientists "seed funding" for their research projects. The new gift will enable the continuation of the award program, which has yielded a 10-to-1 return on investment with grantees securing additional funding from other agencies, including the National Institutes of Health and more than $200 million in total grants from the California Institute for Regenerative Medicine, the state's stem cell agency.

"The Broads' generous support has been essential to the development of new therapies that are currently in, or very near, clinical trials for treating blindness, sickle cell disease and cancer," said Dr. Owen Witte, director of the Broad Stem Cell Research Center. "The Broad Stem Cell Research Center's work, supported by critical philanthropic and other resources, is quickly being translated from basic scientific discoveries into new cellular therapies that will change the practice of medicine and offer future treatment options for diseases thought to be incurable, such as muscular dystrophy, autism and AIDS."

The $2 million gift to the Division of Digestive Diseases builds on nearly $6 million in previous commitments from The Broad Foundation since 2003.

The gifts have enabled the division to develop a comprehensive research and clinical enterprise focused on inflammatory bowel disease, one of only a few such centers in the world. Earning a multifold return for The Broad Foundation's initial investments, these grants have enabled investigators to secure $11 million in funding from pharmaceutical companies, the National Institutes of Health and nonprofit foundations.

In addition, The Broad Foundation's Broad Medical Research Program has provided more than $600,000 in grants to UCLA researchers over the past decade for the study of inflammatory bowel disease.

The new gift will support the Center for Inflammatory Bowel Diseases and research led by Dr. Charalabos "Harry" Pothoulakis, the center's director. Pothoulakis' team conducts research aimed at identifying the molecular mechanisms involved in the development of this group of chronic debilitating diseases, for which there is no cure.

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$4 Million from Eli and Edythe Broad Foundation Will Support UCLA Research

Knee arthritis 9 months after stem cell therapy by Dr Harry Adelson
Carol describes her outcome from stem cell therapy by Dr Harry Adelson for her arthritic knee http://www.docereclinics.com.

By: Harry Adelson, N.D.

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Knee arthritis 9 months after stem cell therapy by Dr Harry Adelson - Video

A service dog that has come from the brink of death and back was in Terry on Wednesday to receive cutting-edge stem cell therapy.

Davis Hawn said his dog, Booster, saved his life and now he's working to return the favor.

"With Booster by my side, I greet each day knowing we can change the world for the better," Hawn said.

Together, Hawn and Booster helped foster international relations by appearing on TV in Cuba. They reassured Thai orphans infected with the HIV virus that life will be OK and they are loved. The list of accomplishments continued to grow until Booster developed hip dysplasia.

"When Booster couldn't get off the floor, I couldn't get out of bed," said Hawn, who suffers from depression. "Just as assuredly as God put Booster into my life, He again answered the call when I read about the modern day marvel of stem-cell implantation."

Medivet America, a global leader in veterinary science with more than 1,000 clinics in 28 countries, learned of Booster's plight and jumped in to help.

"They arranged to perform a procedure in which they injected Booster's own stem cells into his hips and got him back up and running again," Hawn said. "When I went to pay the bill, they refused to accept payment. I like to say that God paid the bill."

In January 2013, Booster again faced a health battle. He was diagnosed with squamous cell carcinoma and given three weeks to live. An aggressive tumor had eaten through Booster's skull cap and left him writhing in pain. In an effort to save Booster's life, Hawn moved to Florida where the University of Florida operated on Booster and a referral clinic performed radiation therapy.

The University of Minnesota took a piece of the tumor that was removed from Booster and used it to developed the first vaccine for squamous cell carcinoma in dogs.

Booster is now a cancer survivor.

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Service dog receives cutting-edge stem cell therapy

April Flowers for redOrbit.com Your Universe Online

A new study, from the Stanford University School of Medicine and Montana State University, demonstrates that, when implanted into the reproductive system of a mouse model, stem cells created from adult, infertile men will yield primordial germ cells. Primordial germ cells normally become sperm cells.

The findings, published in Cell Reports, help to further our understanding of a genetic cause of male infertility and basic sperm biology. The research team says that their approach holds considerable potential for clinical applications.

All of the infertile male participants suffer from a genetic mutation that prevents their bodies from producing mature sperm. The study suggests that the men with this condition called azoospermia might have produced germ cells at some point in their early lives, but these cells were lost as the men matured to adulthood.

Our results are the first to offer an experimental model to study sperm development, said Renee Reijo Pera of the Institute for Stem Cell Biology & Regenerative Medicine and Montana State University. Therefore, there is potential for applications to cell-based therapies in the clinic, for example, for the generation of higher quality and numbers of sperm in a dish.

It might even be possible to transplant stem-cell-derived germ cells directly into the testes of men with problems producing sperm, she added. Considerable study to ensure safety and practicality is needed, however, before reaching that point.

Infertility is a fairly common problem, affecting between 10 and 15 percent of couples in the US. The researchers say that many men are affected by genetic causes of infertility, most commonly due to the spontaneous loss of key genes on the Y sex chromosome. Until now, the causes of infertility at the molecular level have not been clear.

The fact that the research team was able to create primordial germ cells from the infertile men is very promising, but they note that these stem cells created far fewer of these sperm progenitors than the stem cells of men without the genetic mutations. They are sure, however, that this research provides a much needed model to study the earliest steps of human reproduction.

We saw better germ-cell differentiation in this transplantation model than weve ever seen, said Reijo Pera, former director of Stanfords Center for Human Embryonic Stem Cell Research and Education. We were amazed by the efficiency. Our dream is to use this model to make a genetic map of human germ-cell differentiation, including some of the very earliest stages.

Humans share many cellular and physiological processes with common laboratory animals such as mice or fruit flies. In reproduction, however, there are significant variances, making it challenging to recreate the human reproductive processes in a laboratory setting. In addition, many crucial steps, such as the development and migration of primordial germ cells to the gonads,occur in the relatively short first days or weeks after conception.

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Stem Cells Of Infertile Men Used To Create Preliminary Sperm Cells

Chaiwat Subprasom/Reuters/Corbis

Many companies around the world offer stem-cell treatments to patients with heart disease.

An analysis of clinical studies that use adult stem cells to treat heart disease has raised questions about the value of a therapy that many consider inappropriately hyped.

Early-phase clinical trials have reported that adult stem cells are effective in treating heart attack and heart failure, and many companies are moving quickly to tap into this potentially lucrative market. But a comprehensive study that looked at discrepancies in trials investigating treatments that use patients own stem cells, published this week in the journal BMJ (ref. 1), finds that only trials containing flaws, such as design or reporting errors, showed positive outcomes. Error-free trials showed no benefit at all.

The publication comes as two major clinical trials designed to conclusively test the treatments efficacy are recruiting thousands of patients.

The BMJ paper is concerning because the therapeutic approach is already being commercialized, argues stem-cell researcher Paolo Bianco at the Sapienza University of Rome. Premature trials can create unrealistic hopes for patients, and divert resources from the necessary basic studies we need to design more appropriate treatments.

Therapies that use adult stem cells typically involve collecting mesenchymal stem cells from bone marrow taken from the patients hip bone. The cells are then injected back into the patient, to help repair damaged tissue. Original claims that they differentiated into replacement cells have been rejected2, and many clinicians now believe that the cells act by releasing molecules that cause inflammation, with an attendant growth of oxygen-delivering small blood vessels, in the damaged tissue.

The approach has spawned international commercialization of various forms of the therapy, with companies offering treatments for disorders ranging from Parkinsons disease to heart failure. But the effectiveness of such therapies remains unproven.

I have a lot of hope for regenerative medicine, but our results make me fearful.

The BMJ study, led by cardiologist Darrel Francis at Imperial College London, examined 133 reports of 49 randomized clinical trials published up to April last year, involving the treatment of patients who had had a heart attack or heart failure. It included all accessible randomized studies, and looked for discrepancies in design, methodology and reporting of results.

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Doubts over heart stem-cell therapy : Nature News & Comment

Researchers at Columbia Engineering announced today that they have successfully grown fully functional human cartilage in vitro from human stem cells derived from bone marrow tissue. Their study, which demonstrates new ways to better mimic the enormous complexity of tissue development, regeneration, and disease, is published in the April 28 Early Online edition of Proceedings of the National Academy of Sciences (PNAS).

"We've been able -- for the first time -- to generate fully functional human cartilage from mesenchymal stem cells by mimicking in vitro the developmental process of mesenchymal condensation," says Gordana Vunjak-Novakovic, who led the study and is the Mikati Foundation Professor of Biomedical Engineering at Columbia Engineering and professor of medical sciences. "This could have clinical impact, as this cartilage can be used to repair a cartilage defect, or in combination with bone in a composite graft grown in lab for more complex tissue reconstruction."

For more than 20 years, researchers have unofficially called cartilage the "official tissue of tissue engineering," Vunjak-Novakovic observes. Many groups studied cartilage as an apparently simple tissue: one single cell type, no blood vessels or nerves, a tissue built for bearing loads while protecting bone ends in the joints. While there has been great success in engineering pieces of cartilage using young animal cells, no one has, until now, been able to reproduce these results using adult human stem cells from bone marrow or fat, the most practical stem cell source. Vunjak-Novakovic's team succeeded in growing cartilage with physiologic architecture and strength by radically changing the tissue-engineering approach.

The general approach to cartilage tissue engineering has been to place cells into a hydrogel and culture them in the presence of nutrients and growth factors and sometimes also mechanical loading. But using this technique with adult human stem cells has invariably produced mechanically weak cartilage. So Vunjak-Novakovic and her team, who have had a longstanding interest in skeletal tissue engineering, wondered if a method resembling the normal development of the skeleton could lead to a higher quality of cartilage.

Sarindr Bhumiratana, postdoctoral fellow in Vunjak-Novakovic's Laboratory for Stem Cells and Tissue Engineering, came up with a new approach: inducing the mesenchymal stem cells to undergo a condensation stage as they do in the body before starting to make cartilage. He discovered that this simple but major departure from how things were usually? being done resulted in a quality of human cartilage not seen before.

Gerard Ateshian, Andrew Walz Professor of Mechanical Engineering, professor of biomedical engineering, and chair of the Department of Mechanical Engineering, and his PhD student, Sevan Oungoulian, helped perform measurements showing that the lubricative property and compressive strength -- the two important functional properties -- of the tissue-engineered cartilage approached those of native cartilage. The researchers then used their method to regenerate large pieces of anatomically shaped and mechanically strong cartilage over the bone, and to repair defects in cartilage.

"Our whole approach to tissue engineering is biomimetic in nature, which means that our engineering designs are defined by biological principles," Vunjak-Novakovic notes. "This approach has been effective in improving the quality of many engineered tissues -- from bone to heart. Still, we were really surprised to see that our cartilage, grown by mimicking some aspects of biological development, was as strong as 'normal' human cartilage."

The team plans next to test whether the engineered cartilage tissue maintains its structure and long-term function when implanted into a defect.

"This is a very exciting time for tissue engineers," says Vunjak-Novakovic. "Stem cells are transforming the future of medicine, offering ways to overcome some of the human body's fundamental limitations. We bioengineers are now working with stem cell scientists and clinicians to develop technologies that will make this dream possible. This project is a wonderful example that we need to 'think as a cell' to find out how exactly to coax the cells into making a functional human tissue of a specific kind. It's emblematic of the progress being driven by the exceptional young talent we have among our postdocs and students at Columbia Engineering."

The study was funded by the National Institutes of Health (National Institute for Biomedical Imaging and Bioengineering, National Institute for Dental and Craniofacial Research, and National Institute for arthritis and musculoskeletal diseases).

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Stem cells made from the skin of adult, infertile men yield primordial germ cells -- cells that normally become sperm -- when transplanted into the reproductive system of mice, according to researchers at the Stanford University School of Medicine and Montana State University.

The infertile men in the study each had a type of genetic mutation that prevented them from making mature sperm -- a condition called azoospermia. The research suggests that the men with azoospermia may have had germ cells at some point in their early lives, but lost them as they matured to adulthood.

Although the researchers were able to create primordial germ cells from the infertile men, their stem cells made far fewer of these sperm progenitors than did stem cells from men without the mutations. The research provides a useful, much-needed model to study the earliest steps of human reproduction.

"We saw better germ-cell differentiation in this transplantation model than we've ever seen," said Renee Reijo Pera, PhD, former director of Stanford's Center for Human Embryonic Stem Cell Research and Education. "We were amazed by the efficiency. Our dream is to use this model to make a genetic map of human germ-cell differentiation, including some of the very earliest stages."

A difficult process to study

Unlike many other cellular and physiological processes, human reproduction varies in significant ways from that of common laboratory animals like mice or fruit flies. Furthermore, many key steps, like the development and migration of primordial germ cells to the gonads, happen within days or weeks of conception. These challenges have made the process difficult to study.

Reijo Pera, who is now a professor of cell biology and neurosciences at Montana State University, is the senior author of a paper describing the research, published May 1 in Cell Reports. The experiments in the study were conducted at Stanford, and Stanford postdoctoral scholar Cyril Ramathal, PhD, is the lead author of the paper.

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

The germ cells made from stem cells stopped differentiating in the mice before they produced mature sperm (likely because of the significant differences between the reproductive processes of humans and mice) regardless of the fertility status of the men from whom they were derived. However, the fact that the infertile men's cells could give rise to germ cells at all was a surprise.

Previous research in mice with a similar type of infertility found that although they had germ cells as newborns, these germ cells were quickly depleted. The Stanford findings suggests that the infertile men may have had at least a few functioning germ cells as newborns or infants. Although more research needs to be done, collecting and freezing some of this tissue from young boys known to have this type of infertility mutation may give them the option to have their own children later in life, the researchers said.

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Stem cells from some infertile men form germ cells when transplanted into mice

Skin grown in the laboratory can replace animals in drug and cosmetics testing, UK scientists say.

A team led by King's College London has grown a layer of human skin from stem cells - the master cells of the body.

Stem cells have been turned into skin before, but the researchers say this is more like real skin as it has a permeable barrier.

It offers a cost-effective alternative to testing drugs and cosmetics on animals, they say.

The outermost layer of human skin, known as the epidermis, provides a protective barrier that stops moisture escaping and microbes entering.

Scientists have been able to grow epidermis from human skin cells removed by biopsy for several years, but the latest research goes a step further.

The research used reprogrammed skin cells - which offer a way to produce an unlimited supply of the main type of skin cell found in the epidermis.

They also grew the skin cells in a low humidity environment, which gave them a barrier similar to that of true skin.

Skin barrier

Lead researcher Dr Dusko Ilic, of King's College London, told BBC News: "This is a new and suitable model that can be used for testing new drugs and cosmetics and can replace animal models.

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Human Skin Grown In Lab 'Can Replace Animal Testing'