Late-Breaking Basic Science Research Presented at American Heart Association Scientific Sessions Shows Stem Cell Treatment Restores Heart Function Damaged by Muscular Disease

Contact: Sally Stewart Email: sally.stewart@cshs.org

Los Angeles - Nov. 17, 2014 Researchers at the Cedars-Sinai Heart Institute have found that injections of cardiac stem cells might help reverse heart damage caused by Duchenne muscular dystrophy, potentially resulting in a longer life expectancy for patients with the chronic muscle-wasting disease.

The study results were presented today at a Breaking Basic Science presentation during the American Heart Association Scientific Sessions in Chicago. After laboratory mice with Duchenne muscular dystrophy were infused with cardiac stem cells, the mice showed steady, marked improvement in heart function and increased exercise capacity.

Duchenne muscular dystrophy, which affects 1 in 3,600 boys, is a neuromuscular disease caused by a shortage of a protein called dystrophin, leading to progressive muscle weakness. Most Duchenne patients lose their ability to walk by age 12. Average life expectancy is about 25. The cause of death often is heart failure because the dystrophin deficiency leads to cardiomyopathy, a weakness of the heart muscle that makes the heart less able to pump blood and maintain a regular rhythm.

"Most research into treatments for Duchenne muscular dystrophy patients has focused on the skeletal muscle aspects of the disease, but more often than not, the cause of death has been the heart failure that affects Duchenne patients," said Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute and study leader. "Currently, there is no treatment to address the loss of functional heart muscle in these patients."

During the past five years, the Cedars-Sinai Heart Institute has become a world leader in studying the use of stem cells to regenerate heart muscle in patients who have had heart attacks. In 2009, Marbn and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the experimental stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

Earlier this year, Heart Institute researchers began a new study, called ALLSTAR, in which heart attack patients are being infused with allogeneic stem cells, which are derived from donor-quality hearts. Recently, the Heart Institute opened the nations first Regenerative Medicine Clinic, designed to match heart and vascular disease patients with appropriate stem cell clinical trials being conducted at Cedars-Sinai and other institutions.

"We are committed to thoroughly investigating whether stem cells could repair heart damage caused by Duchenne muscular dystrophy," Marbn said.

In the study, 78 lab mice were injected with cardiac stem cells. Over the next three months, the lab mice demonstrated improved pumping ability and exercise capacity in addition to a reduction in heart inflammation. The researchers also discovered that the stem cells work indirectly, by secreting tiny fat droplets called exosomes. The exosomes, when purified and administered alone, reproduce the key benefits of the cardiac stem cells.

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LA JOLLA (CNS) - Two scientists with UC San Diego were awarded a combined $2.7 million in grants from the California Institute for Regenerative Medicine to pursue their studies on stem cell therapies, the school announced Monday.

Shyni Varghese, an associate professor in the Department of Bioengineering and director of the Bio-Inspired Materials and Stem Cell Engineering Laboratory, received a $1.4 CIRM grant to improve the function of transplanted stem cells.

Shaochen Chen, a professor in the Department of Nanoengineering in the Jacobs School of Engineering and a member of UCSD's Institute of Engineering in Medicine, received $1.3 million to develop three-diminensional bioprinting techniques that use heart muscle cells derived from human embryonic stem cells to create new cardiac tissue.

The awards were part of almost $30 million in grants announced at CIRM's monthly meeting in San Francisco, according to UCSD.

"Sometimes even the most promising therapy can be derailed by a tiny problem," said Jonathan Thomas, chairman of the CIRM Board of Directors. "These awards are designed to help find ways to overcome those problems, to bridge the gaps in our knowledge and ensure that the best research is able to keep progressing and move out of the lab and into clinical trials in patients."

Varghese's lab focuses on the interactions of cells with their surrounding micro-environment, and how the conditions necessary to promote normal, healthy survival and growth occur, according to UCSD.

Chen's studies focus on using stem cells to create new heart tissue that would help patients when transplants aren't immediately available.

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UCSD scientists awarded $2.7M grants for stem cell research

What Happens When Stem Cells Go Into My Heart?
Renowned cardiologist, stem cell therapy expert and Okyanos Chief Science Officer Leslie Miller, MD, FACC, explains the importance of generating new blood ve...

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What Happens When Stem Cells Go Into My Heart? - Video

Cardiac Muscle Derived from Pluripotent Stem Cells

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Cardiac Muscle Derived from Pluripotent Stem Cells - Video

Duchenne Muscular Dystrophy May Be Helped With Cardiac Stem Cells
Study shows cardiac stem cells used to treat heart attacks may also help children with muscular dystrophy. Dr. Bruce Hensel reports for the NBC4 News at 5 on...

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Duchenne Muscular Dystrophy May Be Helped With Cardiac Stem Cells - Video

Bristol-Myers Squibb Co. (BMY: Quote) has entered into a clinical collaboration agreement with Eli Lilly and Co. (LLY: Quote) to explore combination regimens from its immuno-oncology portfolio with other mechanisms of action that may accelerate the development of new treatment options for patients.

As per the agreement terms, a phase 1/2 trial will evaluate Bristol-Myers Squibb's approved immunotherapy Opdivo in combination with Lilly's investigational Galunisertib as a potential treatment option for patients with advanced (metastatic and/or unresectable) glioblastoma, hepatocellular carcinoma and non-small cell lung cancer.

Opdivo is approved by FDA for intravenous use for the treatment of patients with unresectable or metastatic melanoma while Galunisertib is currently under investigation as an oral treatment for advanced/metastatic malignancies, including phase 2 evaluation in hepatocellular carcinoma, myelodysplastic syndromes (MDS), glioblastoma, and pancreatic cancer.

In other related news, Lilly has also entered into a collaboration agreement with Merck & Co. Inc. (MRK: Quote) to evaluate the safety, tolerability and efficacy of Merck's KEYTRUDA in combination with Lilly compounds in multiple clinical trials.

Merck's KEYTRUDA was granted accelerated approval by FDA last September for unresectable or metastatic melanoma with disease progression following Ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

BMY closed Tuesday's trading at $63.12, up 1.51%.

Celsus Therapeutics plc (CLTX: Quote) has completed enrollment in its phase II study evaluating the safety and efficacy of MRX-6 cream 2% in a pediatric population with mild to moderate atopic dermatitis.

The topline data from the trial are expected by end-February, 2015.

CLTX closed Tuesday's trading 10.39% higher at $5.95.

Cellular Dynamics International (ICEL: Quote) has entered into a research collaboration with privately-held Cord Blood Registry to reprogram newborn stem cells into induced pluripotent stem cells.

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LLY Collaborates With BMY And MRK, CLTX On Watchlist, ZLTQ Continues To Grow

TUCSON Dr. Zain Khalpey stands next to a ghostly white lung pumping rhythmically on the table next to him. Thats pretty damn good, actually, Khalpey says as he gazes at the data recorded by the lungs ventilator.

The ventilator indicates that the pig lung is inflating and deflating like a normal lung. Experiments such as this bring research a step closer to the operating room.

Khalpey, an associate professor of surgery at the University of Arizona, focuses his research on making more organs available to patients who need a transplant. Every day, 18 people on organ transplant lists die, according to the U.S. Department of Health and Human Services.

In Arizona patients have to wait two to three years for a lung transplant, according to the U.S. National Library of Medicine. This waiting period is emotionally and financially draining for patients.

Khalpey is trying to shrink the wait time. He is taking damaged organs and refurbishing them so they end up in a needy patients body. Other organs too damaged to be refurbished are stripped of their cells and used to grow new organs with the patients stem cells.

In the future, donor organs may not even be needed. Khalpey is working on hybrid organs that are 3-D printed and then seeded with the patients stem cells.

From London

to Tucson

Khalpeys passion for transplant surgery started on a rainy day in 1990s London. A 16-year-old boy lay on the operating table about to undergo a heart-and-lung transplant. Cystic fibrosis caused his lungs to become a breeding ground for infection that whittled away his ability to breathe.

A team of surgeons replaced the boys lungs as well as his heart because he was more likely to survive with donor organs. The medical team rushed the boys viable heart to a second operating room, where it gave new life to another patient.

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Research looks to build organ stockpiles

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Newswise Researchers Recreate Stem Cells From Deceased Patients to Study Present-Day Illnesses Cedars-Sinai research scientists have developed a novel method to re-create brain and intestinal stem cells from patients who died decades ago, using DNA from stored blood samples to study the potential causes of debilitating illnesses such as inflammatory bowel disease. The lab research, published in the journal STEM CELLS Translational Medicine, could yield new therapies for people who suffer from aggressive motor-neuron and gut-related conditions that proved fatal to the deceased patients who long-ago volunteered their blood samples. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Cedars-Sinai Heart Institute Physician-Researcher Awarded National Heart, Lung, and Blood Institute Grant to Develop Prevention Strategies for Deadly Heart Condition One of medicines most prominent experts in sudden cardiac arrest has received a new $2.36 million grant to study how to better predict the deadly heart condition that kills an estimated 300,000 Americans each year. Over recent years, Sumeet S. Chugh, MD, and his team of researchers in the Cedars-Sinai Heart Institute have identified several risk factors for sudden cardiac arrest, including levels of sex hormones in the blood, genetics and electrical and structural abnormalities of the heart. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Study Shows More Patients With Lou Gehrigs Disease Have Genetic Origin Than Previously Thought Genetics may play a larger role in causing Lou Gehrigs disease than previously believed, potentially accounting for more than one-third of all cases, according to one of the most comprehensive genetic studies to date of patients who suffer from the condition also known as amyotrophic lateral sclerosis, or ALS. The study, conducted by investigators at Cedars-Sinai and Washington University in St. Louis, also showed that patients with defects in two or more ALS-associated genes experience disease onset about 10 years earlier than patients with single-gene mutations. CONTACT: Sandy Van, 808-526-1708; Email sandy@prpacific.com

Computer System More Effective Than Doctors at Producing Comprehensive Patient Reports A computer system was more effective than doctors at collecting information about patient symptoms, producing reports that were more complete, organized and useful than narratives generated by physicians during office visits, according to a Cedars-Sinai study. Investigators said the research, published in the American Journal of Gastroenterology, highlights the potential of computers to enhance the quality of medical care and improve outcomes by harnessing accurate and thorough patient information. CONTACT: Duke Helfand, 310-248-6608; Email: duke.helfand@cshs.org

Double Lung Transplant Patient Pays Tribute to Donors Family in the Rose Parade Hours before receiving a lung transplant he thought would never happen, Michael Adams told his surgical team at Cedars-Sinai that hed be happy to live just one more year. Adams, 51, had suffered from cystic fibrosis since he was a baby. Hed been in and out of hospitals for as long as he could remember. By Thanksgiving of 2002, the former wheelchair company worker had end-stage disease. His lungs barely worked. Even eight liters of oxygen left him gasping for air. Then Adams received the call that saved his life: Two healthy lungs had suddenly become available. They belonged to a 15-year-old boy who had been shot and killed on the steps of his church 78 miles away in San Bernardino. Adams was transferred immediately to Cedars-Sinai, where he underwent a double lung transplant. He and his transplant surgeons are available for interviews CONTACT: Laura Coverson, 310-423-5215 Email: laura.coverson@cshs.org

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Cedars-Sinai Medical Tip Sheet for Jan., 2015

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun. Reminding broken hearts how to mend them selves. After years of tracking down the right genetic buttons a team at the Salk Institute in La Jolla has taught a mammal to do what zebra fish do naturally, repair a severely damaged heart. While all our cells have the genetic code for building whole organs those genes seem to be switched off in all higher animals, but active in some more primitive species like zebra fish and salamanders.

New cells (red) repairing injury in a zebra fish heart.

When, with CIRM funding, they inserted genetic signals to turn off those genes in the mice, they saw significant repair of the damaged heart. There are many steps between this advance and getting human hearts to repair them selvesnotably finding a way to introduce the genetic signals without using the virus used in this study. HealthCanal picked up the institutes press release.

Cloned stem cells pretty much like reprogrammed stem cells. In the early days of stem cell research there was a great deal of excitement about the possibility of creating stem cells that genetically match a patient by a process commonly called cloning. This process of taking the genetic storehouse of a cell, the nucleus, and inserting it into a donor egg had been relatively easy in mice. But it turned out quite difficult in humans and was only accomplished last year.

During the years of failed attempts at this process known as nuclear transfer in humans an alternative came into the field. The Nobel prize-winning discovery that you can reprogram any adult cell to act like an embryonic stem cell gave us a new way to create personalized stem cells that genetically match a patient. But ever since that 2008 advance, the research community has fretted over whether those new stem cells called iPS cells really match embryonic stem cells. The iPS cells came from older cells that had lived through many opportunities for mutation and the genetic factors used to reprogram them added further opportunities for mutation.

Researchers at the New York Stem Cell Foundations in house lab have now compared the two types of cells with several layers of genetic analysis. They found the same level of mutation in the iPS cells and the cells from nuclear transfer lending some reassurance to the use of iPS cells going forward. HealthCanal ran the foundations press release.

A more efficient way to make cloned stem cells. Even though a team in Oregon overcame the obstacles to creating stem cells by nuclear transfer last year, and the feat has been repeated by the New York team above and others, it remains terribly inefficient. So, several groups are working on better ways to make these potentially valuable cells.

A former colleague now at Childrens Hospital, Boston wrote a nice explanation of how researchers are going about making these cloned cells easier in the hospitals blog, Vector. Stem cells reduced seizures. The seizures endured by people with many forms of epilepsy originate from genetic defects in their nerves. So, a team at McClean Hospital outside of Boston implanted healthy nerves grown from embryonic stem cells in mice with genetically linked seizures. Half the mice no longer had seizures and the other half had their seizure frequency reduced.

The type of nerves transplanted are called interneurons, which are known to be the nerves that reduce firing of signals. In epilepsy nerve signals are hyperactive. The team is now working on methods to mature the stem cells into purer populations of just the desired interneurons. ClinicalSpace picked up the hospitals press release.

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Stem cell stories that caught our eye: heart repair ...

At Stem Cell Treatment Institute advanced stem cell procedures are performed at some of the most scientifically advanced hospitals in the world. Our Heart Disease treatment differs from standard methods by attacking the root cause inside the heart. Stem cell therapy is focused on affecting physical changes in the heart that can improve a patient's quality of life.

Most Heart Failure patients are treated by IV; injecting the stem cells into the blood which transports them up the heart.

Another procedure, by which the stem cells are surgically implanted directly into the heart, with angiography is also available.

Treatment using Bone Marrow Stem Cells First bone marrow is collected from the patient's iliac crest (hip bone) using thin-needle puncture under local anesthesia. Once the bone marrow collection is complete, patients may return to their hotel and go about normal activities.

The stem cells are then processed in a state-of-the-art laboratory. In the lab, both the quantity and quality of the stem cells are measured.

The stem cells are then implanted back into the patient by IV or surgical implantation.

Cost: Stem cell treatments begin around $13,500 (adults).

To contact us and learn more Click Here >>>

As we age our stem cells become less prolific and less effective. For this reason younger cells are often preferred. We do not need to go all the way back to an early stage embryo to get young cells. Young cells can be used from The Placenta, or Umbilical Cord (cord blood cells), and other young sources. These young cells are more likely than stem cells found in adult sources like bone marrow and adipose tissue (fat) to have proliferative properties. This means that stem cells found in placenta and cord blood have a greater ability to regenerate. In some counrties (US and Europe) requlations limit access to these advanced stem cell sources. Fortunately our International Health Department Permit, a COFEPRIS, is on a Presidential level, insuring access to the highest level of quality stem cells.

Begin the evaluation and scheduling process now! Click Here >>>

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Stem Cell Treatment for Heart Disease

HEART DISEASE & HEART ATTACK Helped With Your OWN STEM CELLS Watch these Heart Repair VIDEOS .. and Review All your Stem Cell Options for Heart Attacks

Heart disease can be helped and controlled with your own Stem Cells. REVIEW and Investigate All your NATURAL Adult Stem cell Options.

Just 2 Patented Stem Cell Enhancer capsules, release 3 to 4 Million New STEM CELLS into your blood stream within 60 Minutes.. Your very OWN Adult Stem Cells can Help prevent and repair Heart Attacks with NO Injections.. NO Surgery .. NO Controversy .. No Hospitals...

Stem Cells help heart disease .. Witness Stem Cell Enhancer capsules HERE !

Heart disease patients with clogged arteries and severe chest pain who were injected with stem cells from their own bone marrow had a small improvement in blood flow and the pumping ability of their hearts, along with an easing of pain, researchers found.

Doctors in the Netherlands drew bone marrow from the hips of heart disease patients in the study. After isolating the stem cells, they injected them back into the patients hearts and monitored their progress. The results were published in the Journal of the American Medical Association.(JAMA)

Go HERE and see a VIDEO of HOW your OWN Adult Stem cells repair your Body)...

FACT : To treat a range of conditions, and several thousand heart disease patients have been treated with adult stem cells, those found in mature organs. While some cardiologists originally hoped bone marrow cells might generate new heart muscle to replace damaged tissue, that hasnt been found to occur, said Warren Sherman, a cardiologist at Columbia University in New York.

The focus has shifted, said Sherman, in a telephone interview today. Cardiologists are now hoping that bone marrow stem cells can promote the growth of new blood vessels and improve the quality of life and level of chest pain patients have. The new study, in 50 heart disease patients, showed that adult stem cells can improve blood flow and ease chest pain, Sherman said. In the study, half of the heart disease patients got their own stem cells and the others got a simulated treatment. The cardiologists used a catheter, a thin wire threaded through their arteries that also carried a small camera to guide the injections. Go Review and investigate healthy heart and heart wellness stem cell options HERE

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heart disease helped with own Adult Stem Cells and Stem ...

Cardiovascular diseases remain the biggest cause of deaths worldwide, though over the last two decades, cardiovascular mortality rates have declined in many high-income countries but have increased at an astonishingly fast rate in low- and middle-income countries. The percentage of premature deaths from cardiovascular disease range from 4% in high-income countries to 42% in low-income countries. More than 17 million people died from cardiovascular diseases in 2008. Each year, heart disease kills more Americans than cancer. In recent years, cardiovascular risk in women has been increasing and has killed more women than breast cancer.

Measures to prevent cardiovascular disease may include:

A fairly recent emphasis is on the link between low-grade inflammation that hallmarks atherosclerosis and its possible interventions. C-reactive protein (CRP) is a common inflammatory marker that has been found to be present in increased levels in patients at risk for cardiovascular disease. Also osteoprotegerin which is involved with regulation of a key inflammatory transcription factor called NF-B has been found to be a risk factor of cardiovascular disease and mortality. Studies have shown that Stem Cells have shown the ability to reduce inflammation.

Streaming NIH Database:

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Stem Cell Treatment Heart Disease - ASCI - Asian Stem Cell ...

With recruitment that started in mid-2013, Cardio3 BioSciences has enrolled 240 patients in less than 18 months, ahead of schedule. As usual in clinical trials targeting severe indications, the Company will continue to recruit additional patients in anticipation of patient dropouts. The CHART-1 trial is currently ongoing in 12 countries in Europe and Israel.

The CHART-1 (Congestive Heart failure Cardiopoietic Regenerative Therapy) trial represents the worlds first Phase III trial for a pre-programmed cellular therapy for the treatment of heart failure.

Dr Christian Homsy, CEO of Cardio3 BioSciences, said: We are extremely pleased to have enrolled the 240thpatient of CHART-1, ahead of schedule. This represents a major achievement for the entire team involved in this trial and I am proud we succeeded in achieving this key operational objective this year. The CHART-1 trial remains solidly on track, with the interim futility readout scheduled for the end of March 2015 and the readout of the full dataset a year later. This accomplishment demonstrates our clinical expertise and gives us confidence for the upcoming CHART-2 trial, to be initiated soon in the U.S.

*** END ***

About CHART-1

CHART-1 is the Companys first Phase III clinical trial, intended to assess in Europe, the efficacy of C-Cure as a treatment for heart failure of ischemic origin. The CHART-1 Phase III trial is a prospective, multi-centre, randomized, sham-controlled, patient-and evaluator-blinded study comparing treatment with C-Cure to a sham treatment. The trial requires the recruitment of a minimum of 240 patients with chronic advanced symptomatic heart failure. The primary endpoint of the trial is a composite endpoint including mortality, morbidity, quality of life, Six Minute Walk Test and left ventricular structure and function at nine months post-procedure. The CHART-1 trial is currently ongoing in 11 countries in Europe (Sweden, Ireland, the United Kingdom, Belgium, Serbia, Bulgaria, Hungary, Spain, Italy, Poland, Switzerland) and Isral.

About C-Cure

Cardio3 BioSciences C-Cure therapy involves taking stem cells from a patients own bone marrow and through a proprietary process called Cardiopoiesis, re-programming those cells to become heart cells. The cells, known as cardiopoietic cells, are then injected back into the patients heart through a minimally invasive procedure, with the aim of repairing damaged tissue and improving heart function and patient clinical outcomes. C-Cure is the outcome of multiple years of research conducted at Mayo Clinic (Rochester, Minnesota, USA), Cardio3 BioSciences (Mont-Saint-Guibert, Belgium) and Cardiovascular Centre in Aalst (Aalst, Belgium).

To subscribe to Cardio3 BioSciences newsletter, visit http://www.c3bs.com. Follow us on Twitter @Cardio3Bio.

About Cardio3 BioSciences

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Cardio3 Biosciences Announces the Enrolment of the 240th Patient for Its Chart-1 Phase III Clinical Trial for the ...

Two men in landmark heart stem cell study tell their stories.

WebMD Archive

Jim Dearing of Louisville, Ky., one of the first men in the world to receive heart stem cells, might have helped start a medical revolution that could lead to a cure for heart failure.

Three years after getting the experimental stem cell procedure, following two heart attacks and heart failure, Dearings heart is working normally.

2012 WebMD, LLC. All rights reserved.

The difference is clear and dramatic -- and it's lasting, according to findings now being made public for the first time.

Dearing first showed "completely normal heart function" on an echocardiogram done in 2011, says Roberto Bolli, MD, who is leading the stem cell trial at the University of Louisville. Those results have not been published before.

That was still true in July 2012, when Dearing again showed normal heart function on another echocardiogram.

Based on those tests, Bolli says, "Anyone who looks at his heart now would not imagine that this patient was in heart failure, that he had a heart attack, that he was in the hospital, that he had surgery, and everything else."

It's not just Dearing who has benefited. His friend, Mike Jones, who had even more severe heart damage, also got the stem cell procedure in 2009. Since then, scarred regions of his heart have shrunk. His heart now appears leaner and stronger than it was before.

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Stem Cell Research: Heart Stem Cells May Help Heal Hearts ...

Researchers at The University of Queensland are part of a global team that has identified a new type of artificial stem cell.

UQ Associate Professor Christine Wells (right) said Project Grandiose had revealed it could track new ways to reprogram a normal adult cell, such as skin cells, into cells similar to those found in an early embryo.

The development is expected to help researchers explore ways to arrive at new cell types in the laboratory, with important implications for regenerative medicine and stem cell science.

Associate Professor Wells, who leads the Stemformatics stem cell research support unit at UQs Australian Institute for Bioengineering and Nanotechnology, said the project involved a consortium of 50 researchers from Canada, Australia, Korea, the USA and the Netherlands

We all come from just one cell the fertilised egg and this cell contains within its DNA a series of instruction manuals to make all of the many different types of cells that make up our body, AIBN Associate Professor Wells said.

These very early stage cells can now be made in the lab by reversing this process of development.

Our research reveals the new instructions imposed on a cell when this developmental process is reversed.

Project Grandiose is a large-scale research effort to understand what happens inside a cell as it reverts to an artificial stem cell.

The role of the Stemformatics.org group was to help the researchers have access to the vast information and data they generated from the project, Associate Professor Wells said.

Our online data platform is designed to let non-specialists view the genes involved and the many ways they are regulated during cell formation.

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New UQ platform aids stem cell research

A team of scientists that included researchers from UCLA has discovered a novel mechanism of RNA regulation in embryonic stem cells. The findings are strong evidence that a specific chemical modification, or "tag," on RNA plays a key role in determining the ability of embryonic stem cells to adopt different cellular identities.

The team also included scientists from Harvard Medical School, Massachusetts General Hospital and Stanford University.

Published in the journal Cell Stem Cell, the research reveals that depleting or knocking out a key component of the machinery that places this chemical tag -- known both as m6A and N6-methyladenosine -- on RNA significantly blocks embryonic stem cells from differentiating into more specialized types of cells.

A key property of embryonic stem cells is their ability to differentiate into many specialized types of cells. However, instead of marching toward a specific fate when prompted by signals to differentiate, embryonic stem cells that have reduced ability to place m6A become stuck in a sort of suspended animation, even though they appear healthy.

Yi Xing, a UCLA associate professor of microbiology, immunology and molecular genetics, led the informatics analyses and was a co-corresponding author of the paper. Other corresponding authors were Dr. Cosmas Giallourakis, an assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital, and Dr. Howard Chang, a professor of Stanford University's School of Medicine and a Howard Hughes Medical Institute investigator.

The study of naturally occurring chemical modifications on RNAs is part of an emerging field known as epitranscriptomics. The m6A tag is the most commonly occurring modification known to scientists; it is found on RNAs of thousands of protein-coding genes and hundreds of non-coding genes in a typical cell type. The tags may help regulate RNA metabolism by marking them for destruction.

Little was known about the dynamics, conservation and function of m6A in human or mouse embryonic stem cells when the authors began the project. The authors analyzed which RNAs were tagged with m6A and the location of the m6A modifications along RNAs in mouse and human embryonic stem cells.

"Our analysis revealed a high level of conservation of m6A patterns between mice and humans, suggesting that m6A has conserved functions in human and mouse embryonic stem cells," Xing said. "Moreover, RNAs with m6A tags were degraded more rapidly and lived a shorter life in the cell than those without."

The investigators then found a strikingly conserved requirement for the presence of normal levels of m6A for differentiating embryonic stem cells into multiple cell types. Depletion of METTL3, a gene encoding the enzyme that places the m6A tag on RNAs, severely blocked human embryonic stem cells from differentiating into the gut or neural precursors. Deletion of the mouse METTL3 gene also led to a severe block in the ability of embryonic stem cells to differentiate into neural and cardiac lineages.

The study suggests that m6A modifications on RNA make the transition between cell states possible by instructing the cells to physically degrade those RNAs marked by m6A in embryonic stem cells, to allow the cells to become another cell type. However, if the cells can no longer tag RNA for destruction, the cells lose the ability to change. This discovery sheds new light on gene regulation in stem cells.

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Loss of a chemical tag on RNA keeps embryonic stem cells in suspended animation

A decade ago, a dream team of researchers from Pittsburgh to South Korea claimed a medical invention that promised to reshape a culture war.

The scientists said they custom-designed stem cells from cloned human embryos. The scientific breakthrough was celebrated around the globe.

Then the bottom fell out.

A scandal erupted over fabricated data, and University of Pittsburgh biologist Gerald Schatten was forced to pull back the findings. Critics cast the 2004 discovery as a farce, a high-profile fraud that forced the journal Science into a rare retraction in January 2006.

Eight years later, the push to use stem cells as a medical treatment continues, but scholars balk at the suggestion that anyone is trying to make genetically identical individuals.

We're not here to clone human beings, for gosh sakes, said John Gearhart, a stem cell researcher and University of Pennsylvania professor in regenerative medicine. Instead, he said, scholars are working to manipulate stem cells to produce heart cells for cardiac patients, brain cells for neurological patients and other custom transplants that could match a person's genetic makeup.

Schatten's work continues at the Magee-Womens Research Institute at Pitt, where university officials cleared him of scientific misconduct, and he remains a vice chairman for research development. He focuses on educating and training physician-scientists and other scientists, a school spokeswoman wrote in a statement. She said Schatten was traveling and was unable to speak with the Tribune-Review.

Researchers have turned the onetime myth of developing stem cells into reality.

At the Oregon Health and Science University, researchers succeeded by blending unfertilized human eggs with body tissue to mold stem cells. Scholars say the cells could let doctors grow customized organs for transplants and other therapies.

The approach engineered by biologist Shoukhrat Mitalipov's research team last year in Portland is among two that scientists are using to forge laboratory-made stem cells the so-called master cells that can transform into other body parts without relying on donated human embryos. Federal law tightly controls the use of taxpayer money for embryonic research.

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Advances reshape stem cell research

Congestive Heart Failure Treatment Using Stem Cells

Congestive Heart Failureor CHF is a state wherein the heart does not have the capability to properly function as a pump. As a result of the cardiac-malfunction the oxygen pumped into the body is insufficient. Congestive heart failure is generally caused bysimultaneousillnesses. Illnesses that weaken the heart muscle,or diseases that trigger the heart muscles to become stiff, or illnesses that create an increase in oxygen demands for the body which consequently increases the supply for fresh oxygen by the body when the heart is incapable of producing oxygen-rich blood at the level needed.

Congestive heart failure and ishchemic heart disease can have an impact on numerous organs in the body. For instance, the injured areas of the heart directly affected by the sickness does not have the capability to produce enough blood for the kidneys, which then affect their capability to excrete water and salt (sodium). The distressed kidney function may cause the body to retain more fluids than needed by the body. The lungs also may develop pulmonary edema (PE).

PE occurs when the fluid in the lungs diminishes a persons ability to exercise normally. Fluid might likewise accumulate inside the liver, which directly affects it function by impairing the livers capability to create important proteins and also in helping clear the body of harmful elements and/ortoxins. The intestines might also turn out to be much less effective in being able to absorb the vitamins, nutrients and medicines a human needs. The fluids in the body can also accumulate quickly which could result to edema (severe swelling) of the ankles and feet.

An Ejection fraction of 20% would be considered a dangerous level and therefore indicates a highly advanced stage of heart failure. Healthy people usually have ejection fractions in between 52% and 68%.

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Stem Cell Treatment Congestive Heart Failure | CHF Stem ...

Researchers at the Cedars-Sinai Heart Institute have found that injections of cardiac stem cells might help reverse heart damage caused by Duchenne muscular dystrophy, potentially resulting in a longer life expectancy for patients with the chronic muscle-wasting disease.

The study results were presented today at a Breaking Basic Science presentation during the American Heart Association Scientific Sessions in Chicago. After laboratory mice with Duchenne muscular dystrophy were infused with cardiac stem cells, the mice showed steady, marked improvement in heart function and increased exercise capacity.

Duchenne muscular dystrophy, which affects 1 in 3,600 boys, is a neuromuscular disease caused by a shortage of a protein called dystrophin, leading to progressive muscle weakness. Most Duchenne patients lose their ability to walk by age 12. Average life expectancy is about 25. The cause of death often is heart failure because the dystrophin deficiency leads to cardiomyopathy, a weakness of the heart muscle that makes the heart less able to pump blood and maintain a regular rhythm.

"Most research into treatments for Duchenne muscular dystrophy patients has focused on the skeletal muscle aspects of the disease, but more often than not, the cause of death has been the heart failure that affects Duchenne patients," said Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute and study leader. "Currently, there is no treatment to address the loss of functional heart muscle in these patients."

During the past five years, the Cedars-Sinai Heart Institute has become a world leader in studying the use of stem cells to regenerate heart muscle in patients who have had heart attacks. In 2009, Marbn and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the experimental stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

Earlier this year, Heart Institute researchers began a new study, called ALLSTAR, in which heart attack patients are being infused with allogeneic stem cells, which are derived from donor-quality hearts.

Recently, the Heart Institute opened the nation's first Regenerative Medicine Clinic, designed to match heart and vascular disease patients with appropriate stem cell clinical trials being conducted at Cedars-Sinai and other institutions.

"We are committed to thoroughly investigating whether stem cells could repair heart damage caused by Duchenne muscular dystrophy," Marbn said.

In the study, 78 lab mice were injected with cardiac stem cells. Over the next three months, the lab mice demonstrated improved pumping ability and exercise capacity in addition to a reduction in heart inflammation. The researchers also discovered that the stem cells work indirectly, by secreting tiny fat droplets called exosomes. The exosomes, when purified and administered alone, reproduce the key benefits of the cardiac stem cells.

Marbn said the procedure could be ready for testing in human clinical studies as soon as next year. The process to grow cardiac-derived stem cells was developed by Marbn when he was on the faculty of Johns Hopkins University. Johns Hopkins has filed for a patent on that intellectual property and has licensed it to Capricor, a company in which Cedars-Sinai and Marbn have a financial interest. Capricor is providing funds for the ALLSTAR clinical trial at Cedars-Sinai.

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Cardiac stem cell therapy may heal heart damage caused by Duchenne muscular dystrophy

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Section: Animal Cell Technology

Enhanced cardiac differentiation of mouse embryonic stem cells by use of the slow-turning, lateral vessel (STLV) bioreactor

Sasitorn Rungarunlert Nuttha Klincumhom Istvan Bock Csilla Nemes Mongkol Techakumphu Melinda K. Pirity Andras Dinnyes

S. Rungarunlert N. Klincumhom I. Bock Cs. Nemes MK. Pirity A. Dinnyes BioTalentum Ltd., Aulich Lajos u. 26. H-2100, Godollo, Hungary

S. Rungarunlert N. Klincumhom M. Techakumphu Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand

I. Bock A. Dinnyes Molecular Animal Biotechnology Laboratory, Szent Istvan University, H-2100 Gdll, Hungary Corresponding author: andras.dinnyes@biotalentum.hu; Phone: +36/20/510-9632, Fax: +36/28/526-151

Emails: Sasitorn Rungarunlert nut_vs@yahoo.com Nuttha Klincumhom nuttha.klincumhom@biotalentum.hu Istvan Bock istvan.bock@biotalentum.hu Csilla Nemes csilla.nemes@biotalentum.hu Mongkol Techakumphu Mongkol.T@chula.ac.th Melinda K. Pirity melinda.pirity@biotalentum.hu

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Abstract Embryoid body (EB) formation is a common intermediate during in vitro differentiation of pluripotent stem cells into specialized cell types. We have optimized the slow-turning, lateral vessel (STLV) for large scale and homogenous EB production from mouse embryonic stem cells. The effects of inoculating different cell numbers, time of EB adherence to gelatin-coated dishes, and rotation speed for optimal EB formation and cardiac differentiation were investigated. Using 3x105 cells/ml, 10 rpm rotary speed and plating of EBs onto gelatin-coated surfaces three days after culture, were the best parameters for optimal size and EB quality on consequent cardiac differentiation. These optimized parameters enrich cardiac differentiation in ES cells when using the STLV method.

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Enhanced cardiac differentiation of mouse embryonic stem ...