Archive for May, 2012

Washington, May 25 : Researchers have identified a single gene that simultaneously controls inflammation, accelerated aging and cancer.

The principal investigator of the study is Robert J. Schneider, PhD, the Albert Sabin Professor of Molecular Pathogenesis, associate director for translational research and co-director of the Breast Cancer Program at NYU Langone Medical Center.

"This was certainly an unexpected finding," said Schneider.

"It is rather uncommon for one gene to have two very different and very significant functions that tie together control of aging and inflammation. The two, if not regulated properly, can eventually lead to cancer development. It's an exciting scientific find," he stated.

For decades, the scientific community has known that inflammation, accelerated aging and cancer are somehow intertwined, but the connection between them has remained largely a mystery, Dr. Schneider said.

What was known, due in part to past studies by Schneider and his team, was that a gene called AUF1 controls inflammation by turning off the inflammatory response to stop the onset of septic shock. But this finding, while significant, did not explain a connection to accelerated aging and cancer.

When the researchers deleted the AUF1 gene, accelerated aging occurred, so they continued to focus their research efforts on the gene. Now, more than a decade in the making, the mystery surrounding the connection between inflammation, advanced aging and cancer is finally being unravelled.

The current study revealed that AUF1, a family of four related genes, not only controls the inflammatory response, but also maintains the integrity of chromosomes by activating the enzyme telomerase to repair the ends of chromosomes, thereby simultaneously reducing inflammation, preventing rapid aging and the development of cancer, Dr. Schneider explained.

"AUF1 is a medical and scientific trinity. Nature has designed a way to simultaneously turn off harmful inflammation and repair our chromosomes, thereby suppressing aging at the cellular level and in the whole animal."Dr. Schneider said.

With this new information, Dr. Schneider and colleagues are examining human populations for specific types of genetic alterations in the AUF1 gene that are associated with the co-development of certain immune diseases, increased rates of aging and higher cancer incidence in individuals to determine exactly how the alterations manifest and present themselves clinically.

Read the original here:
Gene behind chronic inflammation, accelerated aging and cancer identified

ScienceDaily (May 24, 2012) A new type of male contraceptive could be created thanks to the discovery of a key gene essential for sperm development.

The finding could lead to alternatives to the conventional male contraceptives that rely on disrupting the production of hormones, such as testosterone. These treatments can cause side-effects such as irritability, mood swings and acne.

Research, led by the University of Edinburgh, has shown how a gene -- Katnal1 -- is critical to enable sperm to mature in the testes.

If scientists can regulate the Katnal1 gene in the testes, they could prevent sperm from maturing completely, making them ineffective without changing hormone levels.

The research, which is published in the journal PLoS Genetics, could also help in finding treatments for cases of male infertility when malfunction of the Katnal1 gene hampers sperm development.

Dr Lee Smith, Reader in Genetic Endocrinology at the University of Edinburgh's Centre for Reproductive Health, said: "If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive.

"The important thing is that the effects of such a drug would be reversible because Katnal1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm.

"Although other research is being carried out into non-hormonal male contraceptives, identification of a gene that controls sperm production in the way Katnal1 does is a unique and significant step forward in our understanding of testis biology."

Scientists found that male mice that were modified so they did not have the Katnal1 gene were infertile.

Further investigation showed that this was because the gene was needed to allow the sperm to develop and mature.

Continue reading here:
New type of male contraceptive? Key gene essential for sperm development discovered

(CBS News) A male birth control pill might not be so far-fetched, now that Scottish scientists have uncovered a key gene essential for sperm development.

The gene - called Katnal1 - is critical for sperm production because it enables sperm to mature in the testes. Thus, if scientists can somehow regulate this gene with a pill, sperm production will be stalled.

"If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive," study author Dr. Lee Smith, a reader in genetic endocrinology at the Medical Research Council Center for Reproductive Health at the University of Edinburgh in Scotland, said in a news release.

16 worst birth control mistakes Scientists zap sperm counts with ultrasound: Next male birth control? Fertility killers: 11 things that sock it to sperm

Non-hormonal is important, the researchers say, because some conventional male contraceptives that rely on disrupting production of the male hormone testosterone can cause side effects such as mood swings, acne and irritability. The new treatment would also provide an alternative to popular male birth control methods like condoms and vasectomy.

Katnal1 is needed to regulate scaffold-like structures called tubules, the study showed, which forms part of the cells that provide nutrients to developing sperm. When scientists genetically modified mice to not carry this gene, the mice were infertile. The findings are published in the May 24 issue of PLoS Genetics.

Smith said the effects from a drug targeting this gene would be reversible since it stops the sperm at the maturation stage.

"The important thing is that the effects of such a drug would be reversible because Katnal1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm," he said.

Dr. Allan Pacey, a senior lecturer in andrology at the University of Sheffield in the U.K., told BBC News that a non-hormonal contraceptive for men has been the "Holy Grail" of research for years.

"The gene described by the research group in Edinburgh sounds like an exciting new possible target for a new male contraceptive, but it may also shed light on why some men are sub-fertile and why their sperm does not work properly," Pacey said.

Read the original post:
Sperm gene discovery may lead to male birth control

University of Edinburgh researchers say they've identified a gene crucial to sperm development that could be a target for a new form of male birth control.

Oliver Cleve / Getty Images

Condoms or a vasectomy are basically the only contraceptive options currently available for men. But a new gene discovery by infertility researchers at theCentre for Reproductive Healthat the University of Edinburghsuggests that the development of a male contraceptive pill could someday be possible.

While studying infertility in mice, the researchers identified a gene called Katnal1 that appears to be critical during the late stages of sperm production. In the testes,Katnal1 regulates a protein needed by cells that support sperm maturation; without it, sperm do not develop properly and the body disposes of them.

In lab studies, the research team found that mice with genetic mutations that interrupted Katnal1 became infertile.

(MORE:Male Contraception May Be a Reality Sooner than We Think)

Although the research is still in the preliminary stages, the authors say that if a drug could be developed to hinder Katnal1, it could potentially serve as a reversible contraceptive.

If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive, researcherDr. Lee Smith of the University of Edinburgh said in a news release.The important thing is that the effects of such a drug would be reversible because Katnal1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm.

As Dr. Allan Pacey, a senior lecturer in andrology at the University of Sheffield,told BBC News:

The key in developing a non-hormonal contraceptive for men is that the molecular target needs to be very specific for either sperm or other cells in the testicle which are involved in sperm production.

Read more here:
The New Era of Contraception, Thanks to Gene Discovery?

Your DNA may hold valuable information about your health, but current genetic tests can't improve doctors' ability to predict your risk of major disease.

Don Bishop / Getty Images

Our genome the blueprint for what makes us who we are can provide valuable clues about our health and potentially help us predict our risk for various diseases. But a new study shows that knowledge of our DNA isnt actually as revealing as doctors hoped.

In a report published in the American Journal of Human Genetics, scientists at the Harvard School of Public Health found that incorporating genetic information did not improve doctors ability to predict disease risk above and beyond standard risk factors, including things like family history, lifestyle and behavior. So, having detailed genetic information didnt change doctors prevention or treatment plans.

For most people, your doctors advice before seeing your genetic test for a particular disease will be exactly the same as after seeing your tests, Peter Kraft, a co-author of the paper and an epidemiologist at the Harvard School of Public Health, said in a statement.

The researchers looked at risk factors both genetic and environmental for three common, chronic diseases, breast cancer, Type 2 diabetes and rheumatoid arthritis. All conditions are known to be influenced by some genetic and some lifestyle factors. The researchers wanted to determine whether adding information about the interplay of these factors would improve the sensitivity of disease risk prediction.

(MORE: Genetic Testing for Kids: Is It a Good Idea?)

For breast cancer, the scientists created a simulation that included 15 common genetic variants associated with increased risk of the disease, along with environmental factors, such as a womans age at first period, age when she gave birth to her first child and the number of close relatives affected by breast cancer. For Type 2 diabetes, researchers included 31 genetic variants, as well as lifestyle factors like obesity, physical activity, smoking status and family history of diabetes. Finally, for rheumatoid arthritis, they considered 31 genetic variants and two major lifestyle risk factors smoking and breast-feeding.

The researchers analyzed whether interactions among the genes, or interactions between genes and environmental factors, significantly changed the risk profile for any of these diseases. The disease models generated a variety of statistical combinations of genetic and environmental factors, but none produced any marked improvement in predicting disease risk over the lifestyle factors alone.

So, while genome sequencing has become a popular buzzword in medicine, the researchers conclude that given our current limited ability to interpret the genome or understand the complex interplay between genes and environment, getting genetic tests or whole-genome sequencing may not be as helpful as it could be when it comes to informing our health decisions. Even with the current list of 15 genetic variants associated with breast cancer, for example, scientists cant tell which variants are driving disease or are necessary to cause it, and which are merely along for the ride.

Read the rest here:
Why Genetic Tests Don’t Help Doctors Predict Your Risk of Disease

ScienceDaily (May 25, 2012) Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven't known how a deletion in one gene from one parent, called a "hemizygous" deletion, can contribute to cancer.

A research team led by Stephen Elledge, a professor in the Department of Genetics at Harvard Medical School, and his post-doctoral fellow Nicole Solimini, has now provided an answer. The most common hemizygous deletions in cancer, their research shows, involve a variety of tumor suppressing genes called STOP genes (suppressors of tumorigenesis and proliferation) that scatter randomly throughout the genome, but that sometimes cluster in the same place on a chromosome. And these clusters, said Elledge, who is also a professor of medicine at Brigham and Women's Hospital, tend to be deleted as a group. "Eliminating the cluster gives a bigger bang for the deletion buck," he said.

This finding is especially interesting in light of the two-hit model of cancer formation, which holds that both copies of a recessive gene need to be inactivated to trigger a biological effect. Thus the loss of a single tumor suppressor copy should have little or no influence on tumor cell proliferation because the remaining copy located on the other chromosome is there to pick up the slack.

Elledge's research points to a different hypothesis, namely that STOP genes in a hemizygous deletion aren't recessive but are instead haploinsufficient, meaning that they depend on two copies to function normally. "If a tumor suppressor is haploinsufficient, then a single gene copy lacks the potency needed to fully restrain tumorigenesis," Elledge explained, who is also a Howard Hughes Medical Institute Investigator. "So by removing clusters of haploinsufficient genes all at once, the cancer cell immediately propels its growth forward without having to wait for the other copies to also be lost."

Angelika Amon, a professor of biology at the Massachusetts of Technology, said she's surprised by the findings. "We've known from a lot of human syndromes that haploinsufficiency is widespread in the development of complex multicellular organisms," she said. "But these data show it's also critical for individual cells and cell proliferation."

The results also offer a different take on the two-hit model in carcinogenesis, Amon said. Being remarkably unstable, cancer cells can delete gene copies at every turn of the corner. If the loss of a single tumor suppressor copy provides no survival advantage for the tumor, then the tumor has no incentive to retain the cell with that deletion. But if the loss of that copy boosts proliferation, then the probability of a second hit later is greatly increased. "So haploinsufficiency is a way for the cancer cell to dramatically accelerate the acquisition of growth beneficial mutations," Amon said.

In other words, all it takes is a 50 percent reduction in gene activity for a cancer cell to grow. "That tells us it's a lot easier to get cancer than we might have hoped," Amon said.

According to Elledge, the number of hemizygotic deletions averages roughly six per tumor, with some tumors -- breast and pancreatic, for instance -- averaging up to ten. Each deletion involves 25 to 40 genes, many of them STOP genes, but also a few GO genes (growth enhancers and oncogenes) that enhance proliferation. That the STOP genes substantially outnumber their GO counterparts is important, Elledge explained, because it means cancer cells can tilt scales toward proliferation without also compromising it at the same time.

"The data reveal a lot of haploinsufficient players that have small effects individually, but large effects in combination," Elledge said. "Unfortunately, it's not easy to see how to take advantage of that chemotherapeutically."

What's important about the results, he emphasized, is that they open up new views on how tumors evolve. Moreso, they underscore the importance of proliferation as a fundamental feature of tumor growth, he added.

See the original post here:
Cancer may require simpler genetic mutations than previously thought

Washington, May 25 : Detailed knowledge about your genetic makeup'the interplay between genetic variants and other genetic variants, or between genetic variants and environmental risk factors'may only change your estimated disease prediction risk for three common diseases by a few percentage points, which is typically not enough to make a difference in prevention or treatment plans, say researchers.

The study by Harvard School of Public Health (HSPH) researchers is the first to revisit claims in previous research that including such information in risk models would eventually help doctors either prevent or treat diseases.

'While identifying a synergistic effect between even a single genetic variant and another risk factor is known to be extremely challenging and requires studies with a very large number of individuals, the benefit of such discovery for risk prediction purpose might be very limited,' said lead author Hugues Aschard, research fellow in the Department of Epidemiology.

Scientists have long hoped that using genetic information gleaned from the Human Genome Project and other genetic research could improve disease risk prediction enough to help aid in prevention and treatment. Others have been skeptical that such 'personalized medicine' will be of clinical benefit.

Still others have argued that there will be benefits in the future, but that current risk prediction algorithms underperform because they don't allow for potential synergistic effects'the interplay of multiple genetic risk markers and environmental factors'instead focusing only on individual genetic markers.

Aschard and his co-authors, including senior author Peter Kraft, HSPH associate professor of epidemiology, examined whether disease risk prediction would improve for breast cancer, type 2 diabetes, and rheumatoid arthritis if they included the effect of synergy in their statistical models. But they found no significant effect by doing so.

'Statistical models of synergy among genetic markers are not 'game changers' in terms of risk prediction in the general population,' said Aschard.

The researchers conducted a simulation study by generating a broad range of possible statistical interactions among common environmental exposures and common genetic risk markers related to each of the three diseases. Then they estimated whether such interactions would significantly boost disease prediction risk when compared with models that didn't include these interactions since, to date, using individual genetic markers in such predictions has provided only modest improvements.

For breast cancer, the researchers considered 15 common genetic variations associated with disease risk and environmental factors such as age of first menstruation, age at first birth, and number of close relatives who developed breast cancer.

For type 2 diabetes, they looked at 31 genetic variations along with factors such as obesity, smoking status, physical activity, and family history of the disease. For rheumatoid arthritis, they also included 31 genetic variations, as well as two environmental factors: smoking and breastfeeding.

See original here:
Genetic information may not significantly improve disease risk prediction

ScienceDaily (May 24, 2012) Understanding the genetic diversity within and between populations has important implications for studies of human disease and evolution. This includes identifying associations between genetic variants and disease, detecting genomic regions that have undergone positive selection and highlighting interesting aspects of human population history.

Now, a team of researchers from the UCLA Henry Samueli School of Engineering and Applied Science, UCLA's Department of Ecology and Evolutionary Biology and Israel's Tel Aviv University has developed an innovative approach to the study of genetic diversity called spatial ancestry analysis (SPA), which allows for the modeling of genetic variation in two- or three-dimensional space.

Their study is published online this week in the journal Nature Genetics.

With SPA, researchers can model the spatial distribution of each genetic variant by assigning a genetic variant's frequency as a continuous function in geographic space. By doing this, they show that the explicit modeling of the genetic variant frequency -- the proportion of individuals who carry a specific variant -- allows individuals to be localized on a world map on the basis of their genetic information alone.

"If we know from where each individual in our study originated, what we observe is that some variation is more common in one part of the world and less common in another part of the world," said Eleazar Eskin, an associate professor of computer science at UCLA Engineering. "How common these variants are in a specific location changes gradually as the location changes.

"In this study, we think of the frequency of variation as being defined by a specific location. This gives us a different way to think about populations, which are usually thought of as being discrete. Instead, we think about the variant frequencies changing in different locations. If you think about a person's ancestry, it is no longer about being from a specific population -- but instead, each person's ancestry is defined by the location they're from. Now ancestry is a continuum."

The team reports the development of a simple probabilistic model for the spatial structure of genetic variation, with which they model how the frequency of each genetic variant changes as a function of the location of the individual in geographic space (where the gene frequency is actually a function of the x and y coordinates of an individual on a map).

"If the location of an individual is unknown, our model can actually infer geographic origins for each individual using only their genetic data with surprising accuracy," said Wen-Yun Yang, a UCLA computer science graduate student.

"The model makes it possible to infer the geographic ancestry of an individual's parents, even if those parents differ in ancestry. Existing approaches falter when it comes to this task," said UCLA's John Novembre, an assistant professor in the department of ecology and evolution.

SPA is also able to model genetic variation on a globe.

Originally posted here:
Nnew genetic method developed to pinpoint individuals' geographic origin

Option activity on Seattle Genetics, Inc. (SGEN - 20.51) has taken a bullish turn lately, with speculators showing an increased preference for calls over puts. During the past five sessions, traders on the International Securities Exchange (ISE) and Chicago Board Options Exchange (CBOE) have bought to open 2,334 calls on the biotech stock, along with just 96 puts. The resulting five-day call/put volume ratio of 24.31 points to a strong bias for bullish bets over bearish on SGEN.

Broadening our scope to include data from the NASDAQ OMX PHLX (PHLX), SGEN sports a 10-day ISE/CBOE/PHLX put/call volume ratio of 13.45. This ratio ranks higher than 78% of other such readings taken during the previous year, revealing that options traders are purchasing calls over puts at a faster-than-usual pace.

During this same 10-day time frame, open interest at SGEN's June 22.50 call has surged by over 3,000 contracts. This overhead strike is now home to peak front-month call open interest of 5,379 contracts, followed closely by the 5,312 contracts in residence at the June 25 call.

On the charts, SGEN has racked up a healthy gain of 23.5% so far in 2012, easily besting the broader equities market. The shares are currently trading above support at their 10-day and 80-day moving averages, and they're also in the process of establishing a foothold above the round-number $20 level.

However, the stock is trading just below its all-time highs in the $22-22.50 area. This region marked peaks for SGEN throughout the fourth quarter of 2011, and the equity peaked squarely at $21.99 on May 18 before pulling back to trendline support.

With resistance in this area showing no signs of weakening, SGEN is facing an uphill battle as it attempts to chart new record highs. Unfortunately, the glut of out-of-the-money calls at the June 22.50 strike could cause additional trouble for the stock during the short term. As the hedges related to these overhead calls are unwound, the resulting selling pressure could keep SGEN pinned below familiar resistance.

However, that could be exactly what call players are counting on. Short interest accounts for a formidable 27.2% of the stock's float, so it's entirely possible that bears have been buying calls to hedge their shorted shares. This theory is supported by the preference for June 22.50 and 25 calls, since out-of-the-money options provide a cheaper hedge than their in-the-money counterparts.

Read more from the original source:
Can Seattle Genetics Break Through Looming Resistance?

ScienceDaily (May 24, 2012) Severe combined immunodeficiency is defect in the immune system that results in a loss of the adaptive immune cells known as B cells and T cells. Mutations in several different genes can lead to the development of severe combined immunodeficiency, including mutation of the adenosine deaminase (ADA) gene. Traditional treatment options, such as enzyme replacement therapy, are of limited efficacy, but bone marrow transplant from a compatible donor leads to a better response.

A recent clinical trial indicated that gene therapy to insert the correct ADA gene in the patient's own bone marrow cells can also lead to a good response.

However, patients were noted to have defects in B cell tolerance, meaning that some B cells that react to antigens from the body fail to be eliminated, leading to an autoimmune response. Dr. Eric Meffre and colleages at Yale University in New Haven, Connecticut and Alessandro Aiuti in Milan, Italy joined together to better understand why patients developed B cell tolerance problems. They found that loss of the ADA gene directly contributes to B cell tolerance problems and that these defects are mostly corrected after gene therapy.

Their results point to a previously unknown role for ADA in B cell response and support the use of gene therapy as an effective treatment option for ADA-deficient severe combined immunodeficiency patients.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Journal of Clinical Investigation.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

View post:
Gene therapy can correct forms of severe combined immunodeficiency, study suggests

CONTRIBUTED PHOTO Former Zumba instructor Cristina Rodriguez leads a flash mob at La Palmera mall in December 2010, a month before she stopped teaching because she developed a pain in her hip. She later was diagnosed with non-Hodgkin lymphoma. Rodriguez is trying to raise awareness about the importance, especially among Hispanics, of donating bone marrow.

Photo by Rachel Denny Clow, Corpus Christi Caller-Times

Rachel Denny Clow/Caller-Times Cristina Rodriguez sits with her dogs Coby (left) and Flower at her home Thursday. Rodriguez, who has non-Hodgkin lymphoma, is having a Zumba benefit on Sunday and inviting people to register to donate bone marrow. Rodriguez is a former Zumba instructor.

Photo by Rachel Denny Clow, Corpus Christi Caller-Times

Rachel Denny Clow/Caller-Times Cristina Rodriguez sits with her dogs Coby (left) and Flower at her home Thursday.

CORPUS CHRISTI Had Cristina Rodriguez's cancer been more aggressive, had it penetrated her bones, things might have been different.

And while she has had chemotherapy, she has lost her hair and needs a stem cell treatment, but she doesn't need a bone-marrow transplant.

And for that, she's lucky.

Hispanics needing bone marrow have a harder time finding matching donors than do other ethnicities because few Hispanics have registered to donate.

"That could've easily been me," Rodriguez said.

Go here to see the original:
Former Zumba instructor with cancer encourages Hispanics to donate bone marrow

Scientists turn skin cells into healthy heart tissue

Kate Kelland (Reuters) / 26 May 2012

The researchers said there were still many years of testing and refining ahead. But the results meant they might eventually be able to reprogramme patients cells to repair their own damaged hearts.

We have shown that its possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young - the equivalent to the stage of his heart cells when he was just born, said Lior Gepstein, who led the work.

The researchers, whose study was published in the European Heart Journal on Wednesday, said clinical trials of the technique could begin within 10 years.

Heart failure is a debilitating condition in which the heart is unable to pump enough blood around the body. It has become more prevalent in recent decades as advances in medical science mean many more people survive heart attacks. At the moment, people with severe heart failure have to rely on mechanical devices or hope for a transplant.

Researchers have been studying stem cells from various sources for more than a decade, hoping to capitalise on their ability to transform into a wide variety of other kinds of cell to treat a range of health conditions.

There are two main forms of stem cells - embryonic stem cells, which are harvested from embryos, and reprogrammed human induced pluripotent stem cells (hiPSCs), often originally from skin or blood.

Gepsteins team took skin cells from two men with heart failure aged 51 and 61 and transformed them by adding three genes and then a small molecule called valproic acid to the cell nucleus.

They found that the resulting hiPSCs were able to differentiate to become heart muscle cells, or cardiomyocytes, just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for the study.

Here is the original post:
Scientists turn skin cells into healthy heart tissue

Miami, FL (PRWEB) May 26, 2012

Muscle atrophy a major problem with arthritis, could be treated with regenerative medicine, according to A.J. Farshchian MD from the Center for Regenerative Medicine.

Muscle atrophy also known as Muscle wasting Is common in arthritis and is usually due to loss of muscle tissue which could be caused by disease or lack of use. Mostly it is caused from disuse. Some of the other causes of atrophy are: diabetes (diabetic neuropathy) burns poliomyelitis amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) Guillain-Barre syndrome muscular dystrophy myotonia congenita myotonic dystrophy some atrophy that occurs normally with aging cerebrovascular accident (stroke) spinal cord injury peripheral nerve injury (peripheral neuropathy) prolonged immobilization rheumatoid arthritis prolonged corticosteroid therapy

The Center for Regenerative Medicine in Miami, Florida concentrates on helping arthritic and injured people to get back to a functional level of life and their activities using non-surgical techniques and Orthopedic medicine. The center's expertise is in treatment of conditions of spine, knees, shoulders and other cartilage damages. We have developed non-surgical and rehabilitation techniques focused on treatment and management of joint pain. Our team includes health professionals organized around a central theme:

See more here:
Muscle Atrophy, a Major Problem with Arthritis, is Now being Treated at The Center for Regenerative Medicine

Public release date: 25-May-2012 [ | E-mail | Share ]

Contact: Scott LaFee slafee@ucsd.edu 619-543-6163 University of California - San Diego

Five scientists from the University of California, San Diego and its School of Medicine have been awarded almost $12 million in new grants from the California Institute for Regenerative Medicine (CIRM) to conduct stem cell-based research into regenerating spinal cord injuries, repairing gene mutations that cause amyotrophic lateral sclerosis and finding new drugs to treat heart failure and Alzheimer's disease.

The awards mark the third round of funding in CIRM's Early Translational Awards program, which supports projects that are in the initial stages of identifying drugs or cell types that could become disease therapies. More than $69 million in awards were announced yesterday, including funding for first-ever collaboratively funded research projects with China and the federal government of Australia.

"With these new awards, the agency now has 52 projects in 33 diseases at varying stages of working toward clinical trials," said Jonathan Thomas, JD, PhD and CIRM governing board chair. "Californians should take pride in being at the center of this worldwide research leading toward new cures. These projects represent the best of California stem cell science and the best international experts who, together, will bring new therapies for patients."

The five new UC San Diego awards are:

With a $1.8 million award, Lawrence Goldstein, PhD, professor in the Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute Investigator and director of the UC San Diego Stem Cell Program, and colleagues will continue their work developing new methods to find and test drug candidates for Alzheimer's disease (AD). Currently, there is no effective treatment for AD. The researchers screen novel candidates using purified human brain cells made from human reprogrammed stem cells. Already, they have discovered that these human brain cells exhibit a unique biochemical behavior that indicates early development of AD in a dish.

Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Center for Neural Repair at UC San Diego, and colleagues seek to develop more potent stem cell-based treatments for spinal cord injuries. By combining grafts of neural stem cells with scaffolds placed at injury sites, the researchers have reported substantial progress in restoring functional improvement in impaired animal models. The new $4.6 million grant will fund work to identify the optimal human neural stem cells for preclinical development and, in an unprecedented step, test this treatment in appropriate preclinical models of spinal cord injury, providing the strongest validation for human translation.

Amyotrophic lateral sclerosis or ALS (Lou Gehrig's disease) is a progressive neurological condition that is currently incurable. Gene Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine, and colleagues will use a $1.6 million grant to exploit recent discoveries that specific mutations in RNA-binding proteins cause neuronal dysfunction and death. They will use neurons generated from patient cells containing the mutations to identify the unique RNA "signature" of these doomed neurons and screen for drug-like compounds that bypass the mutations to correct the RNA signature to obtain healthy neurons.

Eric David Adler, MD, an associate clinical professor of medicine and cardiologist, studies heart failure, including the use of stem cells to treat it. His $1.7 million award will fund research into Danon disease, a type of inherited heart failure that frequently kills patients by their 20s. Adler and colleagues will turn stem cells created from skin cells of patients with Danon disease into heart cells, then screen hundreds of thousands of drug candidates for beneficial effects. The most promising drugs will subsequently be tested on mice with a genetic defect similar to Danon disease, with the ultimate goal of identifying a suitable candidate for human clinical trials. The research may have broader applications for other conditions with similar pathogenesis, such as cancer and Parkinson's disease.

See more here:
UC San Diego researchers receive new CIRM funding

Five UC San Diego scientists have received almost $12 million combined from the California Institute for Regenerative Medicine to pay for stem cell-based research, the university announced today.

A team led by Lawrence Goldstein, of the Department of Cellular and Molecular Medicine and director of the UC San Diego Stem Cell Program, was given $1.8 million to continue looking for new methods to find and test possible medications for Alzheimer's disease, according to UCSD. They use reprogrammed stem cells in their work.

Dr. Mark Tuszynski, professor of neurosciences and director of the Center for Neural Repair, received $4.6 million to develop more potent stem cell-based treatments for spinal cord injuries.

Gene Yeo, assistant professor in the Department of Cellular and Molecular Medicine, was awarded $1.6 million to continue research into treatments for amyotrophic lateral sclerosis. His research hopes to take advantage of recent discoveries about ALS, or Lou Gehrig's disease, which center on mutations in RNA-binding proteins that cause dysfunction and death in neurons.

Dr. Eric David Adler, an associate clinical professor of medicine and cardiologist, was granted $1.7 million to screen potential drugs for Danon disease, a type of inherited heart failure that frequently kills patients by their 20s.

Yang Xu, a professor in the Division of Biological Sciences, was given $1.8 million to research the use of human embryonic stem cells to produce a renewable source of heart muscle cells that replace cells damaged or destroyed by disease, while overcoming biological resistance to new cells.

"With these new awards, the (institute) now has 52 projects in 33 diseases at varying stages of working toward clinical trials,'' said Jonathan Thomas, chairman of the CIRM governing board. "Californians should take pride in being at the center of this worldwide research leading toward new cures.''

CIRM was established in November 2004 with voter passage of the California Stem Cell Research and Cures Act. UC San Diego has received $112 million since CIRM began providing grants six years ago.

Here is the original post:
UC San Diego Scientists Net $12 Million For Stem Cell Research

DUARTE, Calif.--(BUSINESS WIRE)--

City of Hope was granted a $5,217,004 early translational research award by the California Institute for Regenerative Medicine (CIRM) to support the development of a T cell-based immunotherapy that re-directs a patients own immune response against glioma stem cells. City of Hope has been awarded more than $49.7 million in grant support from CIRM since awards were first announced in 2006.

City of Hope is a pioneer in T cell immunotherapy research, helping to develop genetically modified T cells as a treatment for cancer. This strategy, termed adoptive T cell therapy, focuses on redirecting a patients immune system to specifically target tumor cells, and has the potential to become a promising new approach for treatment of cancer.

In this research, we are genetically engineering a central memory T cell that targets proteins expressed by glioma stem cells, said Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of the T Cell Immunotherapy Research Laboratory. Central memory T cells have the potential to establish a persistent, lifelong immunity to help prevent brain tumors from recurring.

The American Cancer Society estimates that more than 22,000 people in the U.S. will be diagnosed with a brain tumor this year, and 13,700 will die from the disease. Glioma is a type of brain tumor that is often difficult to treat and is prone to recurrence. Currently, less than 20 percent of patients with malignant gliomas are living five years after their diagnosis. This poor prognosis is largely due to the persistence of tumor-initiating cancer stem cells, a population of malignant cells similar to normal stem cells in that they are able to reproduce themselves indefinitely. These glioma stem cells are highly resistant to chemotherapy and radiation treatments, making them capable of re-establishing new tumors.

Researchers at City of Hope previously have identified several proteins as potential prime targets for the development of cancer immunotherapies, such as interleukin 13 receptor alpha 2, a receptor found on the surface of glioma cells, and CD19, a protein that is active in lymphoma and leukemia cells. Both investigational therapies are currently in phase I clinical trials. Forman is the principal investigator for the newly granted study which will develop a T cell that targets different proteins expressed by glioma stem cells. Christine Brown, Ph.D., associate research professor, serves as co-principal investigator, and Michael Barish, Ph.D., chair of the Department of Neurosciences, and Behnam Badie, M.D., director of the Brain Tumor Program, serve as co-investigators on the project.

Because cancer stem cells are heterogeneous, our proposed therapy will target multiple antigens to cast as wide a net as possible over this malignant stem cell population, said Brown.

While in this effort, we are targeting a neurological cancer, our approach will lead to future studies targeting other cancers, including those that metastasize to the brain, added Barish.

The CIRM grant will help us to build a targeted T cell therapy against glioma that can offer lasting protection, determine the best way to deliver the treatment, establish an efficient process to manufacture these T cells for treatment, and get approval for a human clinical trial, said Badie.

City of Hope is also a collaborative partner providing process development, stem cell-derived cell products and regulatory affairs support in two other CIRM-funded projects that received early translational research grants. Larry Couture, Ph.D., senior vice president of City of Hopes Sylvia R. & Isador A. Deutch Center for Applied Technology Development and director of the Center for Biomedicine & Genetics, is working with Stanford University and Childrens Hospital of Orange County Research Institute on their respective projects.

More here:
City of Hope Receives $5 Million Grant to Develop T Cell Treatment Targeting Brain Tumor Stem Cells

Sandy Huffaker/Getty Images

Lab assistant Dave Ferguson holds up stem cell cultures in a lab at the Reeve-Irvine Research Center at the University of California, Irvine.

California has granted a University of California, Irvine researcher nearly $5 million for stem cell research into multiple sclerosis.

The California Institute for Regenerative Medicine issued the grant for the development of a new line of neural stem cells to treat multiple sclerosis, or MS, as its also known.

The disease causes inflammation and loss of fatty tissue that insulates and protects cells in the bodys central nervous system. Researchers at UC Irvine will use the $4.8 million grant to target stem cell treatments designed to both stop the loss of fatty tissue that causes the diseases progression and to encourage new growth of the tissue in order to heal damaged nerves.

The National Multiple Sclerosis Society reports that 400,000 people in the United States suffer from MS, with about 200 new cases diagnosed every week.

Continued here:
UC Irvine stem cell research to receive $4.8 million in state funding

24-05-2012 09:53 For the first time ever, scientists have transformed normal skin cells into healthy beating heart tissue. Researchers based in Haifa in Israel, say they hope that the breakthrough will one day lead to new treatments for patients suffering from heart failure. Head of Research Professor Lior Gepstein "We were able to demonstrate the ability to take skin cells from very sick patients with significant heart failure, heart disease, and show that cells, skin cells from these patients can be eventually differentiated to become healthy heart cells in the dish. So one can take skin cells from a very sick individual, who has very sick heart cells, to reprogram them to become induced pluripotent stem cells and then make heart cells that are healthy, that are young and resemble heart cells at the day that the patient was born." At the moment, people with severe heart failure have to rely on mechanical devices or hope for a transplant. However, by studying stem cells from various sources for more than a decade, researchers are hoping to capitalise on their ability to transform stem cells into a wide variety of other kinds of cell. Head of Research Professor Lior Gepstein "These cells can be transplanted into hearts of animals, survive and function in synchrony with existing heart tissue. This study open the road, hopefully, to future clinical trials, in a decade or so, that will test the ability of such heart cells to repair the patient's own heart," There may be a lot to do before ...

Read more:
Israeli Scientists Reprogram Skin Cells into Beating Heart Tissue: Stem Cell Research Pays Off - Video

SACRAMENTO California's stem cell agency today approved two grants to UC Davis Health System researchers for their innovative work in regenerative medicine.

Kyriacos A. Athanasiou, distinguished professor of orthopaedic surgery and professor and chair of biomedical engineering, and the Child Family Professor of Engineering at UC Davis, is investigating the use of skin-derived stem cells to heal cartilage injuries and debilitating conditions of the knee such as osteoarthritis.

W. Douglas Boyd, professor of surgery, plans to further refine a novel approach to treating cardiovascular injuries suffered during a heart attack by using stem cells and a tissue-like scaffold to repair cardiac damage.

The pair received individual grants totaling approximately $6.6 million from the California Institute for Regenerative Medicine's (CIRM) governing board.

Athanasiou's and Boyd's multi-year grants were among the proposals submitted to CIRM for its third round of Early Translational Awards, which are intended to enable clinical therapies to be developed more rapidly.

"Both of these scientists are conducting exciting research that could have far-reaching implications in health care," said Jan Nolta, director of the UC Davis Institute for Regenerative Cures and the university's stem cell program director. "Dr. Athanasiou is bioengineering new cartilage that could have the same physiological integrity as the cartilage a person is born with. Dr. Boyd is developing a treatment that uses a paper-thin patch embedded with stem cells to harness their regenerative powers to repair damaged heart muscle."

Boyd, who's a pioneering cardiothoracic surgeon, pointed out in his CIRM proposal that heart disease is the nation's number-one cause of death and disability. An estimated 16.3 million Americans over the age of 20 suffer from coronary heart disease, which in 2007 accounted for an estimated 1 in 6 deaths in the U.S. Boyd plans to use bone-marrow derived stem cells -- known as mesenchymal stem cells -- in combination with a bioengineered framework known as an extracellular matrix, to regenerate damaged heart tissue, block heart disease and restore cardiac function, something currently not possible except in cases of a complete and very invasive heart transplant.

An expert in biomedical engineering, Athanasiou is focusing on developing a cellular therapy using stem cells created from an individual's own skin -- known as autologous skin-derived stem cells -- which have shown great promise in animal models. He plans to use the new funding to conduct extensive toxicology and durability tests to determine the technique's long-term safety and efficacy. Such tests are among the many steps needed to advance toward human clinical trials.

Cartilage is the slippery tissue that covers the ends of bones in joints, allowing bones to glide over each other and absorbing the shock of movement. Cartilage defects from injuries and lifelong wear and tear can eventually degenerate into osteoarthritis. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, osteoarthritis is the most common form of arthritis and affects an estimated 27 million Americans over the age of 25.

"For anyone suffering from osteoarthritis or other debilitating cartilage conditions, Dr. Athanasiou's goal of using stem cells to regenerate new tissue could have enormous quality-of-life and economic benefits," said Nolta, who is the recipient of a prior translational grant from CIRM to develop potential therapies for Huntington's disease . "Dr. Boyd's work is equally promising because he's using a bioengineered structure to encourage cardiac tissue repair, which could have important benefits in the treatment of heart disease."

Read more:
State awards stem cell grants to medical researchers

Regenerative medicine company Tengion (NASDAQ:TNGN) has always planned to take its novel tissue generating technology as far as early-stage clinical studies before finding a partner to finance later-stage work.

The companys lead program treating patients who have had their bladder removed is expected to finish phase 1 enrollment by years end. A preclinical kidney program could start human studies next year. CEO John Miclot said his goal is to adhere to those timelines. But therein lies the problem. When Tengion released first quarter financial results, the company said it has $7.3 million in cash left enough to last until September.

Tengions programs are still early stage. But apparently theyre far enough along to catch interest. In further discussing the companys financials, Miclot dropped a hint: We are also actively engaged in discussions with potential strategic partners for both of our leading programs, he said.

The Nasdaq gave Tengion a different warning last week. The exchange said Tengion does not meet the minimum shareholders equity requirement, a measure of the equity stake a companys shareholders have in a company. Tengion has until June 29 to submit a plan to regain compliance with that requirement or face delisting. If the plan is accepted, Tengion would have 180 days from the May 15 notification to regain compliance.

Tengions technology is based on research licensed from Wake Forest Universitys Institute for Regenerative Medicine and the company has made steady scientific progress despite the financial challenges. Tengions Neo-Urinary Conduit program is intended to help bladder cancer patients who have had their bladders removed. Tengion is using its technology to fashion a new conduit to carry urine from the body. Tengions preclinical Neo-Kidney Augment program, intended to help patients who have advanced chronic kidney disease, is moving toward human studies. Miclot said the goal is to file an investigational new drug application with the U.S. Food and Drug Administration in the first half of 2013 with proof of concept data from a phase 1 study expected in 2014.

If the timeline sounds aggressive, it could be because regulators are more comfortable with Tengions technology. Chief Scientific Officer Tim Bertram said on the call that the FDA has reviewed Tengions pre-clinical data from animal studies. The company had run studies on pharmacology work in animals for up to one year. The FDA is now asking the company to do studies in half that time. It illustrates to us their confidence in our work and allows us to proceed quite quickly into humans, Bertram said.

But meeting those timelines will require new financing. If Miclot is talking to potential partners, Medtronic (NYSE:MDT) must be one of them. In March 2011 Tengion raised $31.4 million in a private placement that included the Minnesota medical device maker. As part of the agreement, Medtronic has the right of first refusal to license or acquire Tengions Neo-Kidney Augment program.

Tengion has flirted with the possibility of working with another company before. In Feburary 2011, the company disclosed that discussions with another unnamed publicly-traded company for a stock-for-stock merger had terminated. At the time, the company said it had enough money to last until April of that year. The private placement that included Medtronic came just before Tengion ran out of cash.

Now, the clock is ticking again for Tengion. The company could raise more capital by issuing more stock, but it must first regain Nasdaq compliance. Medtronics rights to license or buy Tengions kidney program expire on October 31, 2013. While Tengions pressing cash needs weaken its negotiating position it can counter with the strong progress made by the kidney program. Tengion has pulled off deals under financial pressure before. By September the company will need to do one again, if not with Medtronic then with someone else.

Read the original post:
Can regenerative medicine firm TNGN conjure a Medtronic partnership?

05/24/2012 . (Classic Rock) Former Iron Maiden singer Paul Di'Anno wants his ex-bandmate Clive Burr to undergo stem cell therapy, despite the costs and risks associated with the procedure.

Burr, the drummer with Maiden from 1979 until 1982, has been in a wheelchair as a result of multiple sclerosis, which has been attacking his nervous system since before he was diagnosed in 2002.

MS reduces the ability of the brain and spinal cord to communicate with each other, resulting in a wide range of potentially severe symptoms. The cause is unknown and there is no cure; but in 2009 researchers made the first breakthrough in reversing symptoms through stem cell therapy.

Di'Anno tells Talking Metal Pirate Radio Burr's condition is "not very good at all." He had a lot to say, read it here.

Classic Rock Magazine is an official news provider for antiMusic.com. Copyright Classic Rock Magazine- Excerpted here with permission.

antiMUSIC News featured on RockNews.info and Yahoo News

...end

See the original post:
Di'Anno Wants Former Iron Maiden Bandmate To Undergo Stem Cell Therapy

Public release date: 24-May-2012 [ | E-mail | Share ]

Contact: Tom Vasich tmvasich@uci.edu 949-824-6455 University of California - Irvine

Irvine, Calif., May 24, 2012 A UC Irvine immunologist will receive $4.8 million to create a new line of neural stem cells that can be used to treat multiple sclerosis.

The California Institute for Regenerative Medicine awarded the grant Thursday, May 24, to Thomas Lane of the Sue & Bill Gross Stem Cell Research Center at UCI to support early-stage translational research.

CIRM's governing board gave 21 such grants worth $69 million to 11 institutions statewide. The funded projects are considered critical to the institute's mission of translating basic stem cell discoveries into clinical cures. They are expected to either result in candidate drugs or cell therapies or make significant strides toward such treatments, which can then be developed for submission to the Food & Drug Administration for clinical trial.

Lane's grant brings total CIRM funding for UCI to $76.65 million.

"I am delighted that CIRM has chosen to support our efforts to advance a novel stem cell-based therapy for multiple sclerosis," said Peter Donovan, director of the Sue & Bill Gross Stem Cell Research Center.

MS is a disease of the central nervous system caused by inflammation and loss of myelin, a fatty tissue that insulates and protects nerve cells. Current treatments are often unable to stop the progression of neurologic disability most likely due to irreversible nerve destruction resulting from myelin deficiencies. The limited ability of the body to repair damaged nerve tissue highlights a critically important and unmet need for MS patients.

In addressing this issue, Lane who also directs UCI's Multiple Sclerosis Research Center will target a stem cell treatment that will not only halt ongoing myelin loss but also encourage the growth of new myelin that can mend damaged nerves.

"Our preliminary data are very promising and suggest that this goal is possible," said Lane, a Chancellor's Fellow and professor of molecular biology & biochemistry. "Research efforts will concentrate on refining techniques for production and rigorous quality control of transplantable cells generated from high-quality human pluripotent stem cell lines, leading to the development of the most therapeutically beneficial cell type for eventual use in patients with MS."

Read more here:
UCI stem cell researcher to receive $4.8 million in state funding

Scientists on Wednesday reported that they have for the first time taken skin cells from heart attacks patients and turned them into healthy heart tissue that could hopefully be used to one day repair damaged heart muscle.

The healthy, beating heart tissue was grown successfully in the lab from human-induced pluripotent stem cells (hiPSCs), and while scientists said they were not safe enough to put back into human patients, they appeared to work well with other cells when implanted into rats. HiPSCs are a recently discovered source far less controversial than use of embryonic stem cells. And, because the transplanted hiPSCs come from the individual, it could resolve the problems seen with tissue and organ rejection.

While the technique has shown promise in rats, the scientists say there are numerous obstacles to overcome and it could take up to ten years or longer before clinical trials could be available for humans. Even so, it is a significant advance in the quest for replacement cell therapy for heart failure patients.

More people are surviving following a heart attack than ever before and therefore the number of people living with a damaged heart and heart failure is increasing, Nicholas Mills, a consultant cardiologist at Edinburgh University, told The Guardian. Unfortunately, the body has only very limited capacity to repair the heart following a heart attack. There is therefore an urgent need to develop effective and safe treatments to regenerate the heart.

Recent research has shown that hiPSCs could be derived from young and healthy people and are capable of transforming into heart cells. However, researchers have not been able to obtain those cells from elderly and diseased patients. And until now, researchers have not been able to show that heart cells created from hiPSCs could integrate with existing heart tissue.

What is new and exciting about our research is that we have shown that its possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to the stage of his heart cells when he was just born, said lead researcher Professor Lior Gepstein, of Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel.

For their study, published in the European Heart Journal, Limor Zwi-Dantsis, a PhD student in the Sohnis Research Laboratory, Gepstein and colleagues took skin cells from two male heart failure patients (ages 51 and 61) and reprogrammed them with three genes (Sox2, Klf4 and Oct4), followed by a small molecule (valproic acid) to the cell nucleus.

The team also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterward to avoid insertional oncogenesis.

Using these methods, the hiPSCs were able to differentiate to become cardiomyocytes (heart muscle cells) just as effectively as hiPSCs that had been developed from healthy, young volunteers. The researchers were then able to make cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. The tissues were beating together within 48 hours, said the researchers.

The researchers transplanted the new tissue into the hearts of healthy rats and found that the grafted tissue started to establish connections with the cells in the host tissue.

Original post:
Human Skin Cells Turned Into Healthy Heart Muscle

On a special surface that could help advance stem cell therapies, UM researchers have turned human skin cells into adult-derived stem cells, coaxed them into bone cells and then transplanted them into holes in the skulls of mice. The cells produced four times as much new bone growth as in the mice without the extra bone cells. In this pink-stained image, the black outline partially encloses the new bone growth in the skull. Image credit: Villa-Diaz, L.G., Brown, S.E., Liu, Y. Ross, A.M., Lahann, J.M., Krebsbach, P.H., University of Michigan

ANN ARBOR University of Michigan researchers have proven that a special surface, free of biological contaminants, allows adult-derived stem cells to thrive and transform into multiple cell types. Their success brings stem cell therapies another step closer.

To prove the cells regenerative powers, bone cells grown on this surface were then transplanted into holes in the skulls of mice, producing four times as much new bone growth as in the mice without the extra bone cells.

An embryos cells really can be anything they want to be when they grow up: organs, nerves, skin, bone, any type of human cell. Adult-derived induced stem cells can do this and better. Because the source cells can come from the patient, they are perfectly compatible for medical treatments.

In order to make them, Paul Krebsbach, professor of biological and materials sciences at the UM School of Dentistry, said, We turn back the clock, in a way. Were taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell.

Specifically, they turn human skin cells into stem cells. Less than five years after the discovery of this method, researchers still dont know precisely how it works, but the process involves adding proteins that can turn genes on and off to the adult cells.

Before stem cells can be used to make repairs in the body, they must be grown and directed into becoming the desired cell type. Researchers typically use surfaces of animal cells and proteins for stem cell habitats, but these gels are expensive to make, and batches vary depending on the individual animal.

You dont really know whats in there, said Joerg Lahann associate professor of chemical engineering and biomedical engineering.

For example, he said that human cells are often grown over mouse cells, but they can go a little native, beginning to produce some mouse proteins that may invite an attack by a patients immune system.

The polymer gel created by Lahann and his colleagues in 2010 avoids these problems because researchers are able to control all of the gels ingredients and how they combine.

Read the original post:
UM: Stem-Cell-Growing Surface Enables Bone Repair

A growth factor isolated from human stem cells shows promising results in a mouse model of multiple sclerosis.

Human mesenchymal stem cells (hMSCs) have become a popular potential therapy for numerous autoimmune and neurological disorders. But while these bone marrow-derived stem cells have been studied in great detail in the dish, scientists know little about how they modulate the immune system and promote tissue repair in living organisms.

Now, one research team has uncovered a molecular mechanism by which hMSCs promote recovery in a mouse model of multiple sclerosis (MS).

According to research, published online Sunday (May 20) in Nature Neuroscience, a growth factor produced by hMSCs fights MS in two ways: blocking a destructive autoimmune response and repairing neuronal damage. The finding could help advance ongoing clinical trials testing hMSCs as a therapy for MS.

The researchers have identified a unique factor that has surprisingly potent activity mediating neuron repair, said Jacques Galipeau, a cell therapy researcher at Emory University in Atlanta, Georgia, who was not involved in the research. The magnitude of the effect on a mouse model of MS is a big deal.

MS is an autoimmune disease in which the immune system attacks myelin sheaths that surround and protect nerve cells. The attack leaves nerves exposed and unable to send signals to the brain and back, resulting in the loss of motor skills, coordination, vision, and cognitive abilities. There is no cure for MS, and most current therapies work to simply suppress the immune system, preventing further neuronal damage. None have demonstrated an ability to also repair damaged myelin and promote recovery.

In 2009, Robert Miller and colleagues at Case Western Reserve University in Cleveland, Ohio, demonstrated that hMSCs dramatically reversed the symptoms of multiple sclerosis in a mouse model of the disorder. The animals got better, recalled Miller. The team hypothesized that the stem cells suppress the immune response and promote remyelination.

But Miller wanted to know exactly what the cells were doing. To find out, his team isolated the medium on which the hMSCs were grown to determine if the cells or something they secreted was responsible for the observed recovery. The medium alone was enough to induce recovery in mice, pointing to the latter.

To find out exactly which molecule or molecules in the medium were responsible, the researchers separated the proteins in the fluid based on the molecular weight and injected each isolate into mice exhibiting symptoms of MS. The mid-weight solution, of proteins with masses between 50 and 100 kilodaltons (kDa), caused recovery. That eliminated a huge number of potential candidates, said Miller.

The researchers then narrowed the field again with a literature search for a molecule that fit their criteria: secreted by hMSCs, 50-100 kDa in size, and involved in tissue repair. They identified hepatocyte growth factor (HGF), a cytokine made by mesenchymal cells that has been shown to promote tissue regeneration and cell survival in numerous experiments. Sure enough, HGF alone was enough to promote recovery in the MS mouse models, and blocking the receptor for HGF in those mice blocked recovery. The team also demonstrated that HGF suppresses immune responses in vivo and accelerates remyelination of neurons in vitro. Finally, they saw that HGF causes remyelination in rats with a lesion on their spinal cord.

See the article here:
Could Stem Cells Cure MS?