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Following a trail of blood: A new diagnostic tool comes of age

February 15th, 2012 5:53 am

Public release date: 14-Feb-2012
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Contact: Joseph Caspermeyer
Joseph.Caspermeyer@asu.edu
Arizona State University

Blood tests have been a mainstay of diagnostic medicine since the late 19th century, offering a wealth of information concerning health and disease. Nevertheless, blood derived from the human umbilical cord has yet to be fully mined for its vital health information, according to Rolf Halden, a researcher at Arizona State University's Biodesign Institute.

In a new study appearing in the journal Environmental Health Perspectives, Halden's team performs detailed analyses of umbilical cord blood (UCB), identifying a total of 1,210 proteins using mass spectroscopy. The findings represent a 6-fold increase in the number UCB proteins thus far described?a significant advance: "Mapping of the full spectrum of proteins detectable in cord blood is the first, crititcal step in the discovery of biomarkers to improve human health," Halden says.

The proteins identified are associated with 138 different metabolic and disease pathways and provide invaluable information for the identification of biomarkers?early warning indices of disease, toxic exposure or disruptions in cellular processes. In addition to presenting intriguing candidates for new biomarkers in UCB, the study also identified 38 proteins corresponding to existing FDA-approved biomarkers for adult blood.

The UCB samples were pooled from 12 newborns, whose maternal backgrounds varied in terms of ethnicity, educational background, body weight, exposure to environmental toxins and also, to cigarette smoke. The research improves prospects for early disease diagnosis, by prioritizing biomarkers based on known proteins linked with disease.

According to Halden, the use of UCB as a diagnostic tool offers a number of attractive advantages. It is a readily acquired diagnostic biofluid?no invasive procedures are needed and relatively large volumes of fluid can be easily obtained. With the aid of modern high-throughput mass spectroscopy, UCB can be rapidly screened to reveal hundreds of proteins in parallel from a single sample having a volume of as small as 1/125th of an ounce. Most importantly, such early screening may provide critical information on likely health trajectories for newborns.

For a wide variety of diseases, early detection offers the best prospect for successful intervention and treatment. Further, many adult afflictions including chronic heart and kidney disease, diabetes and obesity may have their roots in fetal and early childhood development. Previous research has already established a well-documented link between fetal exposure to certain environmental contaminants and unfavorable health outcomes, for example in the case of in utero exposure to cigarette smoke constituents.

Halden's team hoped to expand knowledge of the UCB protein content or proteome, using a limited starting volume of fluid. This is important, as cord blood is a precious resource, exploited for other medical uses. Stem cells obtained from UCB for example are used for bone marrow transplantation and other therapeutic purposes. Once UCB proteins were identified in the tested sample pool, they were compared with known and proposed biomarkers in order to produce a concise list of candidate proteins of diagnostic value in medicine.

The team sought to comprehensively evaluate the diagnostic potential of the UCB proteome, with minimal bias relating to individual health histories. To do this, samples from the 12 newborns were combined into a composite. Among the UCB donors, 6 were African American, 5 were Caucasian and one was Asian.

Of the proteins detected in UCB, around 25 percent were previously detected in adults. Halden's group was able to obtain the protein data with as little as 240 microliters of blood. He emphasizes that new methods for evaluating UCB for newborns are highly desireable, given a spectrum of disorders of rising incidence in the general population, including diabetes, chronic heart and kidney disease and obesity.

The highest priority proteins examined in the current study were those already approved for adult diagnoses by the FDA. These biomarkers include those associated with thyroid deficiencies, chronic kidney dysfunction, and cardiovascular diseases. Future research will determine if such biomarkers are diagnostically appropriate for infants as well.

A second priority was to identify proteins of known function associated with disruptions of normal cell processes. While these proteins have not been FDA approved for diagnostic purposes, they are nevertheless linked with particular diseases or with toxic exposure. These include proteins involved with cardiac arrhythmia and sudden heart failure, maturity onset diabetes of the young (MODY), acute kidney injury, lymphoblastic leukemia, pancreatic cancer and other serious diseases.

Mass spectroscopic analysis of UCB offers the prospect of a global approach to assessing health risks in newborns, allowing the simultaneous observation of numerous indicators of health and disease. The technique should be an invaluable aid to early diagnosis for a range of conditions, with the potential to dramatically improve health outcomes.

###

The study is a multi-institutional effort involving researchers from Arizona State University, Johns Hopkins University, and George Washington University. It was conducted with funding from the National Institute of Environmental Health Sciences (NIEHS).

Rolf Halden is the Associate Director of the Swette Center for Environmental Biotechnology at the Biodesign Institute and Co-Director of the Center for Health Information and Research. He holds a professorship in the School of Sustainable Engineering and the Built Environment at ASU.

Written by: Richard Harth
Science Writer: The Biodesign Institute
richard.harth@asu.edu

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Stem Cells Help Regrow Heart Tissue

February 15th, 2012 5:53 am

Stem cells harvested from a patient's own heart can be used to help repair muscle damaged during a heart attack, according to a preliminary study published online Monday in The Lancet. While it's too soon to know if the technique will help patients live longer, the study is the second small, promising study of cardiac stem cells in three months.

The new study involved 25 patients who had suffered very serious heart attacks; 24% of their heart's major pumping chamber had been replaced by scar tissue. One year later, doctors saw no improvement in those randomly assigned to get standard care. Among the 17 given stem cells, however, "we reversed about half the injury to the heart," said study author Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, in an e-mail. "We dissolved scar and replaced it with living heart muscle."

Warren Sherman, director of stem cell research and regenerative medicine at Columbia University Medical Center in New York, says the study was an important proof of the potential of stem cells - harvested from patients, grown in the lab, then injected back into patients' hearts.

Doctors don't yet know exactly how the stem cells reduce the size of the dead zone of scar tissue, says Kenneth Margulies, director of heart failure and transplant research at the University of Pennsylvania. And while the shrinking suggests that the stem cells are replacing dead cells with living ones, doctors can't definitely prove that without doing a biopsy of the actual cells, he says.

The new study's encouraging results seem to confirm the findings of another small study of heart stem cells, published in The Lancet in November, which also showed an improvement in heart-attack survivors who received the treatment, Margulies says. On the other hand, a third study, found no benefit from stem cells created from patients' own bone marrow.

Four stem-cell patients developed serious complications, compared to only one of the other patients, the study says. That suggests stem-cell therapy has a "satisfactory" safety record, but "is not risk-free," Margulies says.

The idea of regenerating heart tissue "was a pretty far-out idea" only 10 to 20 years ago, Margulies says. There's some evidence that heart tissue is capable of making some small repairs on its own, although not enough to help people who've had a heart attack.

Marban developed the process of growing heart stem cells while working at Johns Hopkins University, which has filed an application for a patent on the idea and licensed it to a company in which Marban has a financial interest. No money from that company was used to pay for the study, which was funded by Cedars-Sinai and the National Institutes of Health.

About 1.3 million Americans have a heart attack each year.

USA Today

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Stem Cells Help Regrow Heart Tissue

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Bioheart Acquires Exclusive Rights to Ageless Regenerative Institute's Adipose Cell Technology

February 15th, 2012 5:51 am

More Topics: Choose a Sector Accounting Firms Advertising/Media/Communications Capital CEO/Board General Business Health/Biotech Internet/Technology Investment Firms Law Firms Mergers & Acquisitions Money Managers People Private Companies Public Companies Venture Capital

Posted February 14, 2012

SUNRISE, Fla., -- Bioheart, Inc. (BHRT.OB) announced today that it has acquired the worldwide exclusive rights to Ageless Regenerative Institute's adipose (fat) derived therapeutic cell technology for use in the cardiac field.

"The Ageless adipose stem cell technology will allow us to broaden our portfolio of product candidates for cardiac patients," said Mike Tomas, President and CEO of Bioheart. "We have successfully treated patients in Mexico and now we are ready to expand into the US."

Adipose tissue is readily available and has been shown to be rich in microvascular, myogenic and angiogenic cells. Bioheart has recently applied to the FDA to begin trials using adipose derived stem cells or LipiCellTM in patients with chronic ischemic cardiomyopathy. Transplantation of LipiCellTM will be accomplished through endocardial implantations with the MyoStarTM Injection Catheter under the guidance of the NOGA® cardiac navigation system by Biosense Webster, Inc. - A Johnson & Johnson Company.

Under the terms of the agreement, Bioheart will have a worldwide exclusive license to all of Ageless technology for use in the heart attack and heart failure markets. The agreement provides for upfront and milestone equity payments to Ageless.

Ageless' President and Chief Executive Officer, Dr. Sharon McQuillan, MD added, "We are excited about this collaboration with Bioheart, a leader in developing cell therapies for cardiovascular disease. Together with Bioheart, we can help to revolutionize cardiovascular medicine and improve the current standard of care for these patients."

About Bioheart, Inc.

Bioheart is committed to maintaining its leading position within the cardiovascular sector of the cell technology industry delivering cell therapies and biologics that help address congestive heart failure, lower limb ischemia, chronic heart ischemia, acute myocardial infarctions and other issues. Bioheart's goals are to cause damaged tissue to be regenerated, when possible, and to improve a patient's quality of life and reduce health care costs and hospitalizations.

Specific to biotechnology, Bioheart is focused on the discovery, development and, subject to regulatory approval, commercialization of autologous cell therapies for the treatment of chronic and acute heart damage and peripheral vascular disease. Its leading product, MyoCell, is a clinical muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart with new living cells for the purpose of improving cardiac function in chronic heart failure patients.

For more information on Bioheart, visit http://www.bioheartinc.com.

About Ageless Regenerative Institute, LLC

The Ageless Regenerative Institute (ARI) is an organization dedicated to the standardization of cell regenerative medicine. The Institute promotes the development of evidence-based standards of excellence in the therapeutic use of adipose-derived stem cells through education, advocacy, and research. ARI has a highly experienced management team with experience in setting up full scale cGMP stem cell manufacturing facilities, stem cell product development & enhancement, developing point-of-care cell production systems, developing culture expanded stem cell production systems, FDA compliance, directing clinical & preclinical studies with multiple cell types for multiple indications, and more. ARI has successfully treated hundreds of patients utilizing these cellular therapies demonstrating both safety and efficacy. For more information about regenerative medicine please visit http://www.agelessregen.com.

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Stem Cells Regrow Healthy Heart Muscle In Heart Attack Patients

February 15th, 2012 5:51 am

Stem cells are proving themselves beneficial once again after scientists used the controversial building blocks to resurrect dead, scarred heart muscle damaged by recent heart attack.

Results from a Cedars-Sinai Heart Institute clinical trial show that treating heart attack patients with an infusion of their own heart-derived cells helps damaged hearts re-grow healthy heart muscle.

Reporting in The Lancet medical journal, the researchers said this is the clearest evidence yet that broken hearts can heal. All that is needed is a little help from one’s own heart stem cells.

“We have been trying as doctors for centuries to find a treatment that actually reverses heart injury,” Eduardo Marban, MD, PhD, and lead author of the study, told WebMD. “That is what we seem to have been able to achieve in this small number of patients. If so, this could change the nature of medicine. We could go to the root of disease and cure it instead of just work around it.”

Marban invented the “cardiosphere” culture technique used to create the stem cells and founded the company developing the treatment.

“These findings suggest that this therapeutic approach is feasible and has the potential to provide a treatment strategy for cardiac regeneration after [heart attack],” wrote University of Hong Kong researchers Chung-Wah Siu and Hung-Fat Tse in an accompanying editorial of Marban’s paper.

The British Heart Foundation told James Gallagher of BBC News that this could “be great news for heart attack patients” in the future.

A heart attack occurs when the heart is starved of oxygen, such as when a clot is blocking the blood flow to the organ. As the heart heals, the dead muscle is replaced by scar tissue, which does not beat like heart muscle. This in turn reduces the hearts ability to pump blood around the body.

Doctors have long been searching for ways to regenerate damaged heart muscle, and now, it seems heart stem cells are the answer. And the Cedars-Sinai trial was designed to test the safety of using stem cells taken from a heart attack patient’s own heart.

The researchers found that one year after receiving the treatment, scar size was reduced from 24 percent to 12 percent of the heart in patients treated with heart stem cells. Patients in the control group, who did not receive stem cells, did not experience a reduction in their heart attack scar tissues.

“While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and re-grow lost heart muscle,” Marban said in a statement. “This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests.”

“These results signal an approaching paradigm shift in the care of heart attack patients,” said Shlomo Melmed, MD, dean of the Cedars-Sinai medical faculty and the Helene A. and Philip E. Hixon Chair in Investigative Medicine. “In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack.”

Marban cautioned that stem cells do not do what people generally think they do. The general idea has been that stem cells multiply over and over again, and, in time, they turn themselves and their daughter cells into new, working heart muscle.

But Marban said the stem cells are actually doing something more amazing.

“For reasons we didn’t initially know, they stimulate the heart to fix itself,” he told Daniel J. DeNoon of WebMD. “The repair is from the heart itself and not from the cells we give them.”

Exactly how the stem cells invigorate the heart to do this was a matter of “feverish research” in the lab.

The CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) clinical trial was part of a Phase I study approved by the US Food and Drug Administration (FDA) and supported by the National Heart, Lung, and Blood Institute.

Marban used 25 volunteer patients who were of an average age of 53 and had recently suffered a heart attack that left them with damaged heart muscle. Each patient underwent extensive imaging scans so doctors could pinpoint the exact location and severity of the scars. Patients were treated at Cedars-Sinai in LA and at Johns Hopkins Hospital in Baltimore.

Eight of the 25 patients served as a control group, receiving conventional medical treatment. The other 17 patients who were randomized to receive the stem cell treatments underwent a minimally invasive biopsy, under local anesthesia. Using a catheter inserted through a vein in the neck, doctors removed a small sample of heart tissue, about half the size of a raisin. The heart tissue was then taken to the lab at Cedars-Sinai and cultured and multiplied the cells using specially developed tools.

The doctors then took the multiplied heart-derived cells — roughly 12 million to 25 million of them per patient — and reintroduced them into the patient’s coronary arteries during another minimally invasive catheter procedure.

The process used in the trial was developed earlier by Marban when he was on the faculty at Johns Hopkins. Johns Hopkins has filed for a patent on the intellectual property and has licensed it to a company in which Marban has a financial interest. However, no funds from that company were used to support the clinical study. All funding was derived from the National Institutes of Health and Cedars-Sinai Medical Center.

This study followed another in which doctors reported using cells taken from the heart to heal the heart. That trial reported in November 2011 that cells could be used to heal the hearts of heart failure patients who were having heart bypass surgery.

And another trial is about to get underway in Europe, which will be the largest ever for stem cell therapy in heart attack patients.

The BAMI trial will inject 3,000 heart attack patients with stem cells taken from their bone marrow within five days of the heart attack.

Marban said despite the heart’s ability to re-grow heart muscle with the help of heart stem cells, they found no increase in a significant measure of the heart’s ability to pump — the left ventricle ejection fraction: the percentage of blood pumped out of the left ventricle.

Professor Anthony Mathur, a coordinating researcher for the upcoming BAMI trial, said that even if the Marban trial found an increase in ejection fraction then it would be the source of much debate. As it was a proof-of-concept study, with a small group of patients, “proving it is safe and feasible is all you can ask.”

“The findings would be very interesting, but obviously they need further clarification and evidence,” he told BBC News.

“It’s the first time these scientists’ potentially exciting work has been carried out in humans, and the results are very encouraging,” Professor Jeremy Pearson, associate medical director at the British Heart Foundation, told BBC News.

“These cells have been proven to form heart muscle in a petri dish but now they seem to be doing the same thing when injected back into the heart as part of an apparently safe procedure,” he added. “It’s early days, and this research will certainly need following up, but it could be great news for heart attack patients who face the debilitating symptoms of heart failure.”

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Broken Hearts Healed with Stem Cells

February 15th, 2012 5:50 am

COMMENTARY | I am willing to bet most people know someone with a damaged heart. I can name two people in my immediate family, but do not have enough fingers and toes to count up all the friends, coworkers and acquaintances who have suffered mild or major heart attacks over the years. The odds are you know several sufferers yourself. In fact, millions of people suffer from heart disease. It is the leading cause of death for Americans.

Re-grow damaged heart tissue

A heart attack causes a piece of the heart tissue to die from lack of blood flow. The scar tissue is all that remains and the person has to deal with the damage. Now, in a ground-breaking study, researchers from the Cedar-Sinai Heart Institute in Los Angeles have discovered a way to re-grow damaged heart muscle.

Stem cell therapy Dr. Eduardo Marban and his team tested stem cell therapy with great results. Out of 17 patients, there was an average reduction of scar tissue by 50 percent. These patients also saw new growth in their heart muscle. Now that is not a total reversal, but for tissue that was presumed lost forever, this is big news.

Marban said, "One of the holy grails in medicine has been the use of medicine to achieve regeneration," Marban said.

Patients' own stem cells

It should be pointed out that the stem cells used did not come from the very controversial embryos, instead the cells used were developed from the patients' hearts. Again, this has huge implications in the treatment of heart disease, and other degenerative diseases for that matter.

"We've achieved what we have achieved using adult stem cells - in this case - actually specifically from a patient's own heart back into the same patient." Marten said, "There's no ethical issues with that - there's no destruction of embryos. There's no reason to worry about immune rejection."

How it works

The process takes several months. A catheter has to first be inserted in the "broken heart" to remove a small biopsy of muscle. The piece is them manipulated in the laboratory and then finally re-injected in the patient's heart. Once the cells take root, the heart will began to mend itself from the inside out.

Far-reaching implications

This revolutionary medical treatment could potentially be used to re-grow damaged kidneys, pancreas or other damaged organs. But, this is only the start of the research. There are still a lot of unknowns in the process. Surprisingly, the stem cells are not doing all the work. "The repair is from the heart itself and not from the cells we give them." said Marban.

Overall the potential for this treatment is great. It will take some more time and study before healing America's broken hearts but the hope is there. Dr. Marban believes the treatment will be available to the general public within four years.

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Dog Receives First-Ever Stem Cell Therapy in Kansas City

February 15th, 2012 5:50 am

Stanley, Kan. — It’s a special Valentine’s Day gift for Jake the dog.  His family gave him a stem cell treatment that they hope will extend his life.

Jake is an 11-year-old yellow lab.  He’s been part of the LeBlanc family since he was a puppy.  Jake’s owner, Elizabeth LeBlanc, calls him her “first baby.”  But then Mia and Aidan were born and at ages eight and five years old, they love to play with Jake.

When the LeBlanc’s noticed Jake was having trouble getting around they wanted to help.  They tried medication, but say it didn’t work for very long.  Then Mia saw a segment about a stem cell treatment for dogs on t.v. and asked if they could get it for Jake.  The LeBlanc’s called their veterinarian and found out the Stanley Veterinary Clinic in Stanley, Kansas is the only place in the metro where they can do the entire procedure in house.

Dr. Les Pelfrey, D.V.M. explained the procedure.

“We’re going to collect about 20 grams of fat surgically and then we’re going to process it in our lab here in house then we’re going to reintroduce those stem cells after we activate them back into the affected joints,” said Dr. Les Pelfrey.

The procedure can cost $3000. The dog’s fatty tissue has to be sent off to a lab for the stem cells to be extracted.  But at the Stanley Veterinary Clinic they can process the stem cells in their own lab, cutting the cost to $1800.00.

Jake’s arthritis is affecting his hips, knees, one elbow and one shoulder.  Dr. Pelfrey made an incision and removed the fatty tissue from Jake.  Then veterinary technician Stephanie Pierce took it to the lab to break it down, cook it and then spin it.  The final product?  Stem cells that were then re-injected into Jake’s joints to help him grow cartilage.  Pierce says Jake will “act like a puppy again as far as moving around.”

The LeBlancs can’t wait to see the results.

“For 12 years he’s given us love and joy so we just want to give him a better quality of life,” LeBlanc said.

Jake will spend the night at the Stanley Veterinary Clinic.  He should be able to head home tomorrow.  Jake and the LeBlancs should notice results in the next few weeks.

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Scarred Hearts Can Be Mended With Stem Cell Therapy

February 15th, 2012 5:50 am

February 15, 2012, 12:06 AM EST

By Ryan Flinn

(Adds comment from researcher in 13th paragraph.)

Feb. 14 (Bloomberg) -- Stem cells grown from patients’ own cardiac tissue can heal damage once thought to be permanent after a heart attack, according to a study that suggests the experimental approach may one day help stave off heart failure.

In a trial of 25 heart-attack patients, 17 who got the stem cell treatment showed a 50 percent reduction in cardiac scar tissue compared with no improvement for the eight who received standard care. The results, from the first of three sets of clinical trials generally needed for regulatory approval, were published today in the medical journal Lancet.

“The findings in this paper are encouraging,” Deepak Srivastava, director of the San Francisco-based Gladstone Institute of Cardiovascular Disease, said in an interview. “There’s a dire need for new therapies for people with heart failure, it’s still the No. 1 cause of death in men and women.”

The study, by researchers from Cedars-Sinai Heart Institute in Los Angeles and Johns Hopkins University in Baltimore, tested the approach in patients who recently suffered a heart attack, with the goal that repairing the damage might help stave off failure. While patients getting the stem cells showed no more improvement in heart function than those who didn’t get the experimental therapy, the theory is that new tissue regenerated by the stem cells can strengthen the heart, said Eduardo Marban, the study’s lead author.

“What our trial was designed to do is to reverse the injury once it’s happened,” said Marban, director of Cedars- Sinai Heart Institute. “The quantitative outcome that we had in this paper is to shift patients from a high-risk group to a low- risk group.”

Minimally Invasive

The stem cells were implanted within five weeks after patients suffering heart attacks. Doctors removed heart tissue, about the size of half a raisin, using a minimally invasive procedure that involved a thin needle threaded through the veins. After cultivating the stem cells from the tissue, doctors reinserted them using a second minimally invasive procedure. Patients got 12.5 million cells to 25 million cells.

A year after the procedure, six patients in the stem cell group had serious side effects, including a heart attack, chest pain, a coronary bypass, implantation of a defibrillator, and two other events unrelated to the heart. One of patient’s side effects were possibly linked to the treatment, the study found.

While the main goal of the trial was to examine the safety of the procedure, the decrease in scar tissue in those treated merits a larger study that focuses on broader clinical outcomes, researchers said in the paper.

Heart Regeneration

“If we can regenerate the whole heart, then the patient would be completely normal,” Marban said. “We haven’t fulfilled that yet, but we’ve gotten rid of half of the injury, and that’s a good start.”

While the study resulted in patients having an increase in muscle mass and a shrinkage of scar size, the amount of blood flowing out of the heart, or the ejection fraction, wasn’t different between the control group and stem-cell therapy group. The measurement is important because poor blood flow deprives the body of oxygen and nutrients it needs to function properly, Srivastava said.

“The patients don’t have a functional benefit in this study,” said Srivastava, who wasn’t not involved in the trial.

The technology is being developed by closely held Capricor Inc., which will further test it in 200 patients for the second of three trials typically required for regulatory approval. Marban is a founder of the Los Angeles-based company and chairman of its scientific advisory board. His wife, Linda Marban, is also a founder and chief executive officer.

“We’d like to study patients who are much sicker and see if we can actually spare them early death, or the need for a heart transplant, or a device,” Eduardo Marban said.

--Editors: Angela Zimm, Andrew Pollack

#<184845.409373.2.1.99.7.25># -0- Feb/14/2012 17:13 GMT

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Stem cell treatments improve heart function after heart attack

February 15th, 2012 5:50 am

ScienceDaily (Feb. 14, 2012) — Stem cell therapy moderately improves heart function after a heart attack, according to a systematic review published in The Cochrane Library. But the researchers behind the review say larger clinical trials are needed to establish whether this benefit translates to a longer life.

In a heart attack, the blood supply to parts of the heart is cut off by a blocked artery, causing damage to the heart tissue. The cells in the affected area start to die. This is called necrosis and in the days and weeks that follow, the necrotic area may grow, eventually leaving a large part of the heart unable to contract and increasing the risk of further heart problems. Stem cell therapy uses cells from the patient's own bone marrow to try to repair and reduce this damage. Currently, the treatment is only available in facilities with links to scientific research.

The authors of the review drew together all the available evidence to ask whether adult bone marrow stem cells can effectively prevent and repair the damage caused by a heart attack. In 2008, a Cochrane review of 13 stem cell therapy clinical trials addressed the same question, but the new review adds 20 more recent trials, drawing its conclusions from all 33. By incorporating longer follow up, the later trials provide a better indication of the effects of the therapy several years after treatment.

The total number of patients involved in trials was 1,765. All had already undergone angioplasty, a conventional treatment that uses a balloon to open the blocked artery and reintroduce the blood supply. The review's findings suggest that stem cell therapy using bone marrow-derived stem cells (BMSCs) can produce a moderate long-term improvement in heart function, which is sustained for up to five years. However, there was not enough data to reach firm conclusions about improvements in survival rates.

"This new treatment may lead to moderate improvement in heart function over standard treatments," said lead author of the study, Enca Martin-Rendon, of the Stem Cell Research laboratory, NHS Blood and Transplant at the John Radcliffe Hospital in Oxford, UK. "Stem cell therapy may also reduce the number of patients who later die or suffer from heart failure, but currently there is a lack of statistically significant evidence based on the small number of patients treated so far."

It is still too early to formulate guidelines for standard practice, according to the review. The authors say further work is required to establish standard methods, including cell dosage, timing of cell transplantation and methods to measure heart function. "The studies were hard to compare because they used so many different methods," said Martin-Rendon. "Larger trials with standardised treatment procedures would help us to know whether this treatment is really effective.

Recently, the task force of the European Society of Cardiology for Stem Cells and Cardiac Repair received funding from the European Union Seventh Framework Programme for Research and Innovation (EU FP7-BAMI) to start such a trial. Principal Investigator for the BAMI trial, and co-author of this Cochrane review, Anthony Mathur, said, ''The BAMI trial will be the largest stem cell therapy trial in patients who have suffered heart attacks and will test whether this treatment prolongs the life of these patients."

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Journal Reference:

E Martin-Rendon, S Brunskill, C Doree, C Hyde, S Watt, A Mathur. Stem cell treatment for acute myocardial infarction. The Cochrane Library, 2012 DOI: 10.1002/14651858.CD006536

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Stem Cells May Help Regenerate Heart Muscle

February 15th, 2012 5:50 am

A promising stem cell therapy approach could soon provide a way to regenerate heart muscle damaged by heart attacks.

Researchers at Cedars-Sinai Heart Institute and The Johns Hopkins University harvested stem cells from the hearts of 17 heart attack patients and after prepping the cells, infused them back into the patients' hearts. Their study is published in the current issue of The Lancet.

The patients received the stem cell infusions about three months after their heart attacks.

Researchers found that six months after treatment, patients had significantly less scarring of the heart muscle and also showed a considerable increase the amount of healthy heart muscle, compared to eight post-heart attack patients studied who did not receive the stem cell infusions. One year after, scar size was reduced by about 50 percent.

"The damaged tissue of the heart was replaced by what looks like healthy myocardium," said Dr. Peter Johnston, a study co-author and an assistant professor of medicine at The Johns Hopkins University School of Medicine. "It's functioning better than the damaged myocardium in the control subjects, and there's evidence it's starting to contract and generate electrical signals the way healthy heart tissue does."

While this research is an early study designed to demonstrate that this stem cell therapy is safe, cardiologists say it's an approach that could potentially benefit millions of people who have suffered heart attacks. Damage to the heart muscle is permanent and irreparable, and little can be done to compensate for loss of heart function.

"In the U.S., six million patients have heart failure, and the vast majority have it because of a prior heart attack," said Johnston.

The damaged scar tissue that results from a heart attack diminishes heart function, which can ultimately lead to enlargement of the heart.

At best, Johnston said, there are measures doctors can try to reduce or compensate for the damage, but in many cases, heart failure ultimately sets in, often requiring mechanical support or a transplant.

"This type of therapy can save people's lives and reduce the chances of developing heart failure," he said.

Cardiac Regeneration A Promising Field

Other researchers have also had positive early results in experiments with stem cell therapy using different types of cells, including bone marrow cells and a combination of bone marrow and heart cells.

"It's exciting that studies using a number of different cell types are yielding similar results," said Dr. Joshua Hare, professor of cardiology and director of the University of Miami Interdisciplinary Stem Cell Institute.

The next steps, he said, include determining what the optimal cell types are and how much of the cells are needed to regenerate damaged tissue.

"We also need to move to larger clinical trials and measure whether patients are improving clinically and exhibiting a better quality of life after the therapy."

In an accompanying comment, Drs. Chung-Wah Siu amd Hung-Fat Tse of the University of Hong Kong wrote that given the promising results of these studies, health care providers will hopefully recognize the benefits that cardiac regeneration can offer.

And Hare added that someday, this type of regeneration can possibly offer hope to others who suffered other types of organ damage.

"This stategy might work in other organs," he said. "Maybe this can work in the brain, perhaps for people who had strokes."

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Bone gives 'some' heart healing

February 15th, 2012 5:50 am

14 February 2012 Last updated at 19:10 ET By James Gallagher Health and science reporter, BBC News

Bone marrow stem cell therapy offers "moderate improvement" to heart attack patients, according to a large UK review of clinical trials.

The analysis by the Cochrane Collaboration looked at 33 trials involving more than 1,700 patients.

It said longer-term studies were needed to see if the experimental therapy affected life expectancy.

The review comes a day after doctors reported the first case of using heart cells to heal heart attack damage.

If a patient survives a heart attack, dead heart muscle is replaced with scar tissue - leaving the patient weaker and possibly on a lifetime of medicine.

Researchers are beginning to show that taking cells from a heart, growing millions of new heart cells in the laboratory and pumping those back into the heart may reduce scar tissue and lead to new heart muscle.

Continue reading the main story “Start Quote

Stem cell therapy may also reduce the number of patients who later die or suffer from heart failure, but currently there is a lack of statistically significant evidence based on the small number of patients treated so far”

End Quote Dr Enca Martin-Rendon Lead researcher

However, the trials are at a very early stage and in only a handful of patients. Using a similar technique with cells taken from the bone marrow, which is a prime source of stem cells, has a much longer pedigree.

The report by Cochrane pooled the data from all 33 bone marrow trials which had taken place up to 2011.

It concluded that bone marrow therapy "may lead to a moderate long-term improvement" in heart function which "might be clinically very important".

Longer life uncertain

It said there was still no evidence of "any significant effect on mortality" in comparison with standard treatment. However, this may be due to the size of the studies and that patients were followed for a short period of time.

Lead author Dr Enca Martin-Rendon, from NHS Blood and Transplant at the John Radcliffe Hospital in Oxford, said: "This new treatment may lead to moderate improvement in heart function over standard treatments.

"Stem cell therapy may also reduce the number of patients who later die or suffer from heart failure, but currently there is a lack of statistically significant evidence based on the small number of patients treated so far."

Prof Anthony Mathur, from Barts and the London School of Medicine and Dentistry, is leading the largest ever trial of stem cells in heart attack patients.

It starts this year, however, he told the BBC that the results could come quite quickly. Three thousand patients across Europe will take part. They will be injected with stem cells five days after a heart attack and then followed for two years to see if the therapy affects life expectancy.

Prof Peter Weissberg, medical director at the British Heart Foundation, said: "This review reflects the consensus of opinion about these trials - cell therapy has a modestly beneficial effect.

"Despite that, no-one knows why, or even if, cell therapies will translate into better survival or sustained improvement in damaged hearts. It's much too early to judge the likely long-term benefits."

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Stem cells – ISWA project – Video

February 14th, 2012 11:32 pm

14-02-2012 08:13 STEM CELLS The dance of life Recent developments in regenerative medicine and modern biology are going to have an enormous impact on our lives. Also the way itself we face the problem of sickness, aging and death changes as the hope (or the illusion?) grows that we always can fight and delay them. Stem cell research is in fact changing our knowledge of the fundamental mechanisms of life and feeding the idea that we can increasingly contrast the cruel natural selection rules which make us fall ill, grow old and die. A new frontier opens and unpredictable changes in our culture are taking place. People's hopes and fears grow at the same time. The general properties of the stem cells is presented, namely the ability to proliferate and, under certain conditions, to differentiate in other types of cells. In this way they can generate a new tissue replacing a damaged one, and also a new organ (like blood, thrachea, liver, heart, skin, cornea and very recently retina). A stamp is shown, which was emitted by the Japanese government to celebrate the discovery of a university team, which was able to regenerate a cornea and giving the opportunity to a patient to see again. Then the innovative results is presented in applications of the stem cells to orthopedy, muscular dystrophy, cardiology and dentistry. Finally the etherogeneus perspectives is presented offered by stem cell research to treat degenerative disorders, like Alzheimer, Parkinson diseases and Multiple Sclerosis. www ...

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Bioheart Acquires Exclusive Rights to Ageless Regenerative Institute’s Adipose Cell Technology

February 14th, 2012 11:32 pm

SUNRISE, Fla., Feb. 14, 2012 (GLOBE NEWSWIRE) -- Bioheart, Inc. (BHRT.OB) announced today that it has acquired the worldwide exclusive rights to Ageless Regenerative Institute's adipose (fat) derived therapeutic cell technology for use in the cardiac field.

"The Ageless adipose stem cell technology will allow us to broaden our portfolio of product candidates for cardiac patients," said Mike Tomas, President and CEO of Bioheart. "We have successfully treated patients in Mexico and now we are ready to expand into the US."

Adipose tissue is readily available and has been shown to be rich in microvascular, myogenic and angiogenic cells. Bioheart has recently applied to the FDA to begin trials using adipose derived stem cells or LipiCell(TM) in patients with chronic ischemic cardiomyopathy. Transplantation of LipiCell(TM) will be accomplished through endocardial implantations with the MyoStar(TM) Injection Catheter under the guidance of the NOGA(R) cardiac navigation system by Biosense Webster, Inc. -- A Johnson & Johnson Company.

Under the terms of the agreement, Bioheart will have a worldwide exclusive license to all of Ageless technology for use in the heart attack and heart failure markets. The agreement provides for upfront and milestone equity payments to Ageless.

Ageless' President and Chief Executive Officer, Dr. Sharon McQuillan, MD added, "We are excited about this collaboration with Bioheart, a leader in developing cell therapies for cardiovascular disease. Together with Bioheart, we can help to revolutionize cardiovascular medicine and improve the current standard of care for these patients."

About Bioheart, Inc.

Bioheart is committed to maintaining its leading position within the cardiovascular sector of the cell technology industry delivering cell therapies and biologics that help address congestive heart failure, lower limb ischemia, chronic heart ischemia, acute myocardial infarctions and other issues. Bioheart's goals are to cause damaged tissue to be regenerated, when possible, and to improve a patient's quality of life and reduce health care costs and hospitalizations.

Specific to biotechnology, Bioheart is focused on the discovery, development and, subject to regulatory approval, commercialization of autologous cell therapies for the treatment of chronic and acute heart damage and peripheral vascular disease. Its leading product, MyoCell, is a clinical muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart with new living cells for the purpose of improving cardiac function in chronic heart failure patients.

For more information on Bioheart, visit http://www.bioheartinc.com.

About Ageless Regenerative Institute, LLC

The Ageless Regenerative Institute (ARI) is an organization dedicated to the standardization of cell regenerative medicine. The Institute promotes the development of evidence-based standards of excellence in the therapeutic use of adipose-derived stem cells through education, advocacy, and research. ARI has a highly experienced management team with experience in setting up full scale cGMP stem cell manufacturing facilities, stem cell product development & enhancement, developing point-of-care cell production systems, developing culture expanded stem cell production systems, FDA compliance, directing clinical & preclinical studies with multiple cell types for multiple indications, and more. ARI has successfully treated hundreds of patients utilizing these cellular therapies demonstrating both safety and efficacy. For more information about regenerative medicine please visit http://www.agelessregen.com.

Forward-Looking Statements: Except for historical matters contained herein, statements made in this press release are forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "to," "plan," "expect," "believe," "anticipate," "intend," "could," "would," "estimate," or "continue" or the negative other variations thereof or comparable terminology are intended to identify forward-looking statements.

Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Also, forward-looking statements represent our management's beliefs and assumptions only as of the date hereof. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.

The Company is subject to the risks and uncertainties described in its filings with the Securities and Exchange Commission, including the section entitled "Risk Factors" in its Annual Report on Form 10-K for the year ended December 31, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2011.

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Scarred Hearts Can Be Mended With Stem Cell Therapy

February 14th, 2012 11:32 pm

February 14, 2012, 3:17 PM EST

By Ryan Flinn

(Adds comment from researcher in 13th paragraph.)

Feb. 14 (Bloomberg) -- Stem cells grown from patients’ own cardiac tissue can heal damage once thought to be permanent after a heart attack, according to a study that suggests the experimental approach may one day help stave off heart failure.

In a trial of 25 heart-attack patients, 17 who got the stem cell treatment showed a 50 percent reduction in cardiac scar tissue compared with no improvement for the eight who received standard care. The results, from the first of three sets of clinical trials generally needed for regulatory approval, were published today in the medical journal Lancet.

“The findings in this paper are encouraging,” Deepak Srivastava, director of the San Francisco-based Gladstone Institute of Cardiovascular Disease, said in an interview. “There’s a dire need for new therapies for people with heart failure, it’s still the No. 1 cause of death in men and women.”

The study, by researchers from Cedars-Sinai Heart Institute in Los Angeles and Johns Hopkins University in Baltimore, tested the approach in patients who recently suffered a heart attack, with the goal that repairing the damage might help stave off failure. While patients getting the stem cells showed no more improvement in heart function than those who didn’t get the experimental therapy, the theory is that new tissue regenerated by the stem cells can strengthen the heart, said Eduardo Marban, the study’s lead author.

“What our trial was designed to do is to reverse the injury once it’s happened,” said Marban, director of Cedars- Sinai Heart Institute. “The quantitative outcome that we had in this paper is to shift patients from a high-risk group to a low- risk group.”

Minimally Invasive

The stem cells were implanted within five weeks after patients suffering heart attacks. Doctors removed heart tissue, about the size of half a raisin, using a minimally invasive procedure that involved a thin needle threaded through the veins. After cultivating the stem cells from the tissue, doctors reinserted them using a second minimally invasive procedure. Patients got 12.5 million cells to 25 million cells.

A year after the procedure, six patients in the stem cell group had serious side effects, including a heart attack, chest pain, a coronary bypass, implantation of a defibrillator, and two other events unrelated to the heart. One of patient’s side effects were possibly linked to the treatment, the study found.

While the main goal of the trial was to examine the safety of the procedure, the decrease in scar tissue in those treated merits a larger study that focuses on broader clinical outcomes, researchers said in the paper.

Heart Regeneration

“If we can regenerate the whole heart, then the patient would be completely normal,” Marban said. “We haven’t fulfilled that yet, but we’ve gotten rid of half of the injury, and that’s a good start.”

While the study resulted in patients having an increase in muscle mass and a shrinkage of scar size, the amount of blood flowing out of the heart, or the ejection fraction, wasn’t different between the control group and stem-cell therapy group. The measurement is important because poor blood flow deprives the body of oxygen and nutrients it needs to function properly, Srivastava said.

“The patients don’t have a functional benefit in this study,” said Srivastava, who wasn’t not involved in the trial.

The technology is being developed by closely held Capricor Inc., which will further test it in 200 patients for the second of three trials typically required for regulatory approval. Marban is a founder of the Los Angeles-based company and chairman of its scientific advisory board. His wife, Linda Marban, is also a founder and chief executive officer.

“We’d like to study patients who are much sicker and see if we can actually spare them early death, or the need for a heart transplant, or a device,” Eduardo Marban said.

--Editors: Angela Zimm, Andrew Pollack

#<184845.409373.2.1.99.7.25># -0- Feb/14/2012 17:13 GMT

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Dog Receives First-Ever Stem Cell Therapy in Kansas City

February 14th, 2012 11:32 pm

KANSAS CITY, Mo. — An 11-year-old yellow Labrador suffering from severe arthritis underwent stem cell therapy on Valentine’s Day. It’s the first time a dog has received in-clinic adult stem cell therapy in Kansas City.

According to Stanley Veterinary Clinic where Jake the dog is being treated, adult animal stem cell technology uses the body`s own regenerative healing power to help cure dogs, cats and horses suffering from arthritis, hip dysplasia and tendon, ligament and cartilage injuries and other ailments.

Fat tissue is removed from the animal, the stem cells are separated from the fat and activated, and then injected into the affected areas.

Within two months of the procedure, Jake should be moving well, with little or no pain.

Severe arthritis affects up to 40 percent of the 164 million dogs and cats in the United States.

As for Jake, FOX 4’s Kim Byrnes will have an update on his condition tonight on FOX 4 News at 5 and 6.

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Stem Cells May Help Regenerate Heart Muscle

February 14th, 2012 11:32 pm

A promising stem cell therapy approach could soon provide a way to regenerate heart muscle damaged by heart attacks.

Researchers at Cedars-Sinai Heart Institute and The Johns Hopkins University harvested stem cells from the hearts of 17 heart attack patients and after prepping the cells, infused them back into the patients' hearts. Their study is published in the current issue of The Lancet.

The patients received the stem cell infusions about three months after their heart attacks.

Researchers found that six months after treatment, patients had significantly less scarring of the heart muscle and also showed a considerable increase the amount of healthy heart muscle, compared to eight post-heart attack patients studied who did not receive the stem cell infusions. One year after, scar size was reduced by about 50 percent.

"The damaged tissue of the heart was replaced by what looks like healthy myocardium," said Dr. Peter Johnston, a study co-author and an assistant professor of medicine at The Johns Hopkins University School of Medicine. "It's functioning better than the damaged myocardium in the control subjects, and there's evidence it's starting to contract and generate electrical signals the way healthy heart tissue does."

While this research is an early study designed to demonstrate that this stem cell therapy is safe, cardiologists say it's an approach that could potentially benefit millions of people who have suffered heart attacks. Damage to the heart muscle is permanent and irreparable, and little can be done to compensate for loss of heart function.

"In the U.S., six million patients have heart failure, and the vast majority have it because of a prior heart attack," said Johnston.

The damaged scar tissue that results from a heart attack diminishes heart function, which can ultimately lead to enlargement of the heart.

At best, Johnston said, there are measures doctors can try to reduce or compensate for the damage, but in many cases, heart failure ultimately sets in, often requiring mechanical support or a transplant.

"This type of therapy can save people's lives and reduce the chances of developing heart failure," he said.

Cardiac Regeneration A Promising Field

Other researchers have also had positive early results in experiments with stem cell therapy using different types of cells, including bone marrow cells and a combination of bone marrow and heart cells.

"It's exciting that studies using a number of different cell types are yielding similar results," said Dr. Joshua Hare, professor of cardiology and director of the University of Miami Interdisciplinary Stem Cell Institute.

The next steps, he said, include determining what the optimal cell types are and how much of the cells are needed to regenerate damaged tissue.

"We also need to move to larger clinical trials and measure whether patients are improving clinically and exhibiting a better quality of life after the therapy."

In an accompanying comment, Drs. Chung-Wah Siu amd Hung-Fat Tse of the University of Hong Kong wrote that given the promising results of these studies, health care providers will hopefully recognize the benefits that cardiac regeneration can offer.

And Hare added that someday, this type of regeneration can possibly offer hope to others who suffered other types of organ damage.

"This stategy might work in other organs," he said. "Maybe this can work in the brain, perhaps for people who had strokes."

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VistaGen Updates Pipeline of Stem Cell Technology-Based Drug Rescue Candidates

February 14th, 2012 11:32 pm

SOUTH SAN FRANCISCO, CA--(Marketwire -02/14/12)- VistaGen Therapeutics, Inc. (OTC.BB: VSTA.OB - News) (OTCQB: VSTA.OB - News), a biotechnology company applying stem cell technology for drug rescue and cell therapy, has identified its initial Top 10 drug rescue candidates and plans to launch two formal drug rescue programs by the end of next quarter.

VistaGen's goal for each of its stem cell technology-based drug rescue programs is to generate and license a new, safer variant of a once-promising large market drug candidate previously discontinued by a pharmaceutical company no earlier than late-preclinical development.

"We are now at an advanced stage in our business model," said Shawn Singh, VistaGen's Chief Executive Officer. "After more than a decade of focused investment in pluripotent stem cell research and development, we are now at the threshold where game-changing science becomes therapeutically relevant to patients and commercially relevant to our shareholders. We have positioned our company and our stem cell technology platform to pursue multiple large market opportunities. We plan to launch two drug rescue programs by the end of the next quarter."

Over the past year, VistaGen, working with its network of strategic partners, identified over 525 once-promising new drug candidates that meet the Company's preliminary screening criteria for heart toxicity-focused drug rescue using CardioSafe 3D™, its human heart cell-based bioassay system. After internally narrowing the field to 35 compounds, VistaGen, working together with its external drug rescue advisors, including former senior pharmaceutical industry executives with drug safety and medicinal chemistry expertise, analyzed and carefully narrowed the group of 35 to the current Top 10.

About VistaGen Therapeutics

VistaGen is a biotechnology company applying human pluripotent stem cell technology for drug rescue and cell therapy. VistaGen's drug rescue activities combine its human pluripotent stem cell technology platform, Human Clinical Trials in a Test Tube™, with modern medicinal chemistry to generate new chemical variants of once-promising small-molecule drug candidates. These are once-promising drug candidates discontinued by pharmaceutical companies during development due to heart toxicity, despite positive efficacy data demonstrating their potential therapeutic and commercial benefits. VistaGen uses its pluripotent stem cell technology to generate early indications, or predictions, of how humans will ultimately respond to new drug candidates before they are ever tested in humans.

Additionally, VistaGen's oral small molecule prodrug candidate, AV-101 (4-Cl-KYN), is in Phase 1b development for treatment of neuropathic pain. Unlike other NMDA receptor antagonists developed previously, AV-101 readily crosses the blood-brain barrier and is then efficiently converted into 7-chlorokynurenic acid (7-Cl-KYNA), one of the most potent and specific glycineB site antagonists currently known, and has been shown to reduce seizures and excitotoxic neuronal death. Neuropathic pain, a serious and chronic condition causing pain after an injury or disease of the peripheral or central nervous system, affects approximately 1.8 million people in the U.S. alone. To date, VistaGen has been awarded over $8.5 million from the NIH for development of AV-101. The Company anticipates pursuing Phase 2 development for neuropathic pain and other neurological indications, including depression, epilepsy, and/or Parkinson's disease in the event it receives additional non-dilutive development grant funding from the NIH or private foundations.

Visit VistaGen at http://www.VistaGen.com, follow VistaGen at http://www.twitter.com/VistaGen or view VistaGen's Facebook page at http://www.facebook.com/VistaGen.

Cautionary Statement Regarding Forward Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the success of VistaGen's stem cell technology-based drug rescue activities, ongoing AV-101 clinical studies, its ability to enter into drug rescue collaborations and/or licensing arrangements with respect to one or more drug rescue variants, risks and uncertainties relating to the availability of substantial additional capital to support VistaGen's research, drug rescue, development and commercialization activities, and the success of its research and development plans and strategies, including those plans and strategies related to AV-101 and any drug rescue variant identified and developed by VistaGen. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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Radiation therapy transforms breast cancer cells into cancer stem cells

February 14th, 2012 6:03 am

Washington, Feb 14 (ANI): Researchers have shown for the first time that radiation treatment -despite killing half of all tumour cells during every cycle - transforms other cancer cells into treatment-resistant breast cancer stem cells.

According to researchers with the UCLA Department of Radiation Oncology at UCLA's Jonsson Comprehensive Cancer Center, the generation of these breast cancer stem cells counteracts the otherwise highly efficient radiation treatment.

If scientists can uncover the mechanisms and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, said study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and Jonsson Cancer Center researcher.

"We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine," said Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA.

"It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment."

"Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects," the study stated.

There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Pajonk and his team eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice.

Using a unique imaging system Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment.

The newly generated iBCSC were remarkably similar to breast cancer stem cells found in tumors that had not been irradiated, Pajonk said.

The team also found that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated.

Pajonk said that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells.

However, if challenged by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumour.

"What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing," Pajonk said.

"The study may carry enormous potential to make radiation even better."

Pajonk stressed that breast cancer patients should not be alarmed by the study findings and should continue to undergo radiation if recommended by their oncologists.

"Radiation is an extremely powerful tool in the fight against breast cancer," he said.

"If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful," Pajonk added.

The study has been published in the online edition of peer-reviewed journal Stem Cells. (ANI)

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Cardiac stem cells can restore heart muscles, says study

February 14th, 2012 6:03 am

They also help to reduce scar size

Infusion of cardiac stem cells into persons who suffered heart attack recently can help to regenerate their heart muscles, says a study published on February 14, in The Lancet.

Phase I of the study was conducted on 17 patients, who received stems cells, and eight, who received standard care (control group), at the Cedars-Sinai Heart Institute in Los Angeles and Johns Hopkins Hospital, Baltimore. All of them had had heart attacks about a month before the study began in May 2009. The stem cells were created from the patients' heart tissues.

Visible improvements were seen in those who received infusion of stem cells, compared with the control group at the end of six months and a year. While no change in the scar size was seen in the control group, there was more than 12 per cent reduction in the size at the end of six months in the treatment group.

As scar size is directly related to scar mass, a reduction of 8.4 gram (28 per cent) and almost 13 gram (42 per cent) in scar mass was seen in the treatment group at the end of six months and 12 months.

Surprisingly, scar mass reduction was accompanied by an increase in viable myocardial mass. In fact, on an average, the increase in viable myocardial mass was “about 60 per cent more than scar reduction.” This is significant as it had led to a “partial restoration of lost left ventricular mass in patients with CDCs [cardiosphere-derived cells],” the authors of the study noted.

The study thus “challenges the conventional wisdom that once established, cardiac scarring is permanent, and that, once lost, healthy heart muscle cannot be restored.”

However, a change in scar size was accompanied by only 2 per cent increase in ejection factor (the amount of blood pumped by the heart), which is not considered significant.

While “the reasons for the discrepancy are unclear,” the study noted that “ejection factor at baseline was only moderately impaired, leaving little room for improvement.”

Of the six patients in the treatment group who had serious adverse events, only one was found to be related to the study.

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Study: Cardiac stem cells can reverse heart attack damage

February 14th, 2012 6:03 am

Dr. Eduardo Marbán, in his laboratory at the Cedars-Sinai Heart Institute. (Cedars-Sinai Heart Institute)

By Eryn Brown, Los Angeles Times / for the Booster Shots blog

February 13, 2012, 5:45 p.m.

Researchers have used cardiac stem cells to regenerate heart muscle in patients who have suffered heart attacks, also known as myocardial infarction.

The small preliminary study, which was conducted by the Cedars-Sinai Heart Institute in Los Angeles, involved 25 patients who had suffered heart attacks in the previous one and a half to three months. 

Seventeen of the study subjects received infusions of stem cells cultured from a raisin-sized chunk of their own heart tissue, which had been removed via catheter. The eight others received standard care. 

During a heart attack, heart tissue is damaged, leaving a scar.  On average, scars in patients who had the stem cell infusions dropped in size from 24% to 12% of the heart, said Dr. Eduardo Marbán, director of the Cedars-Sinai Heart Institute and lead researcher on the study, which was published online Monday in the journal The Lancet.  (The journal has provided an abstract of the study; subscription is required for the full text.)

In an email, Marbán said he believed that the stem cells repaired the damaged heart muscle "indirectly, by stimulating the heart's endogenous capacity to regrow [which normally lies dormant]." He said that the most surprising aspect of the research team's finding was that the heart was able to regrow healthy tissue. Conventional wisdom holds that cardiac scarring is permanent.

A follow-up study involving about 200 patients is planned for later this year, Marbán added.

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Stem Cells Could Help Heal Broken Hearts [Medicine]

February 14th, 2012 6:03 am

Even after recovery, heart attacks can leave a lasting mark on your ticker—scar tissue weakens the muscle and prevents it from functioning as well as it did before seizing up. A pioneering stem-cell procedure, however, could cut the damage in half.

According to the results of a small safety trial by the Cedars-Sinai Heart Institute and published in the Lancet medical journal, introducing stem cells derived from the patient's own heart have shown an "unprecedented" ability to reduce scarring as well as regenerate healthy cardiac tissue.

During a heart attack, the organ is deprived of oxygen and its tissue begins to die off. As the heart heals from the attack, any damaged muscle is replaced by scar tissue, which prevents the heart from beating properly and pumping the requisite blood flow the body needs.

The CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to Reverse ventricUlar dySfunction) study involved 25 patients—eight serving as the control group, the other 17 actually receiving the treatment. Researchers first performed extensive imaging scans to identify location and severity of scarring, then biopsied a half-raisin-sized piece the patient's heart tissue. Doctors then isolated and cultured stem cells from it and injected the lab-grown stem cells—roughly 12-25 million of them—back into the heart.

After a year, scarring in patients that received the treatment decreased by an astounding fifty percent while the control group showed no decrease in scarring. "These results signal an approaching paradigm shift in the care of heart attack patients," said Shlomo Melmed, dean of the Cedars-Sinai medical faculty. The scars were once believed to be permanent but this technique shows promise as a means to regenerate the damaged muscle. It should be noted however, that the heart's ability to pump did not increase as the scar tissue disappeared.

"While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle," Eduardo Marbán, director of the Cedars-Sinai Heart Institute, told PhysOrg. "This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests."

Researchers hope to soon begin an expanded clinical trial and, if the results are as promising as these, eventually use the procedure to assist the US's annual 770,000 coronary disease sufferers. [The Lancet via Physorg - BBC News]

Image: Shortkut / Shutterstock

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