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When a piece of muscle in a person’s heart dies from lack of blood flow, it scars over and is lost.  But a team of researchers from the Cedars-Sinai Heart Institute in Los Angeles has proven that those muscles may not necessarily be gone forever.

In a ground-breaking study that may change how heart attacks are treated, Dr. Eduardo Marban and his team used stem cells to re-grow damaged heart muscle.  In the 17 patients who received the therapy, Marban measured an average 50 percent reduction in the size of the scar tissue

“One of the holy grails in medicine has been the use of medicine to achieve regeneration,” Marban said.  “Patients that were treated not only experienced shrinkage of their scars, but also new growth of their heart muscle, which is very exciting.”

The stem cells were not derived from embryos, but instead were developed from the patients’ own hearts.  Marban’s team inserted a catheter into the diseased hearts and took a small biopsy of muscle.  In the laboratory, the tissue was manipulated into producing stem cells.  After a few weeks of marinating in culture, researchers had enough stem cells to re-inject them into the patients’ hearts.  Over the course of a year, the stem cells took root in cardiac tissue, encouraging the heart to create new muscle and blood vessels.  In other words, the heart actually began to mend itself.

Click here to see an animation of how the process works.

“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.   There’s no ethical issues with that – there’s no destruction of embryos.  There’s no reason to worry about immune rejection."

While similar research has been done using stem cells from bone marrow, this is the first time that stem cells derived from a patient’s own cardiac tissue have been used.

Marban believes this therapy could be broadly used in many of the 5 to 7 million Americans who suffer from heart disease every year.  And he said the applications could go well beyond diseased hearts.

“If we can do that in the heart, I don’t see any reason, conceptually, why we couldn’t do it in kidneys for example, or pancreas or other organs that have very limited regenerative capacity,” Marban said.

While the procedure may be a revolutionary medical technique, there are still a few more puzzling questions about the research that Marban would like to investigate further.  For example, while the patients grew new heart muscle and saw a dramatic reduction in scar tissue, the actual function of their hearts did not show a significant improvement.  And it appeared the stem cells themselves may not have turned into cardiac muscle, but rather they stimulated the heart to produce new muscle cells.

Because this was a “Phase 1” study, it was really meant to measure whether the procedure was safe.  Of the 17 patients who were given the stem cell injections, six experienced “serious adverse events,” but only one was regarded to be possibly related to the treatment.  

The potential success of this research could hold a lot of promise for the millions of Americans who suffer from heart disease each and every year, which is the leading cause of death in the United States.  If his future experiments yield the same results as this initial study, Marban believes he could be offering this therapy to patients within four years – and that could go a long way in mending all of America’s broken hearts.

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Stem cells a fix for 'broken hearts'?

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Main Category: Stem Cell Research
Also Included In: Cardiovascular / Cardiology
Article Date: 15 Feb 2012 - 2:00 PST

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A systematic review of the evidence so far suggests stem cells derived from bone marrow moderately improves heart function after a heart attack. But the authors say larger trials are needed before we can devise guidelines for therapy practice, or draw conclusions about the long-term benefit of the treatment, such as whether it extends life.

The review, about to be published in the Cochrane Library, updates one done in 2008 that reviewed 13 trials; the new one takes into account another 20 more recent trials. Even though these later trials had longer follow ups, it was still not possible to draw firm conclusions about the long term benefits.

Lead author Enca Martin-Rendon, of the Stem Cell Research laboratory, NHS Blood and Transplant at the John Radcliffe Hospital in Oxford, UK, told the press that they found it hard to compare the 33 studies because they used so many different approaches:

"Larger trials with standardised treatment procedures would help us to know whether this treatment is really effective," said Martin-Rendon.

In order to pump blood around the body, the heart also needs its own constant supply of blood. If this supply is cut off by a blocked artery, it can cause a heart attack and damage the muscle tissue in the affected part of the heart, causing the cells to start dying, a process known as necrosis.

In the days and weeks after a heart attack, the necrosis can spread, eventually leaving a large part of the heart muscle unable to perform the job of contracting and pumping as well as it ought to. This increases the risk of further heart problems.

Stem cells are precursor cells that have the potential to mature into any cell in the body, including heart muscle cells. For this review, the researchers looked only at treatments that use stem cells derived from bone marrow. At present, such treatments are only available at centres that do research.

Another recently published study described a treatment that used stem cells derived from the patient's own heart tissue to repair heart attack damage.

For the review, Martin-Rendon and colleagues pooled data on a total of 1,765 patients from 33 trials. All the patients had already undergone the conventional treatment, angioplasty, where a balloon is inflated in the blocked artery to open it up and restore blood flow.

They concluded that stem cell therapy using bone marrow-derived stem cells (BMSCs) can result in a moderate long-term improvement in heart function, that lasts for up to 5 years. But there was not enough data to enable them to say anything firm about the effect on survival rates.

Martin-Rendon said:

"This new treatment may lead to moderate improvement in heart function over standard treatments," adding that:

"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."

The authors said it was still to early to compile guidelines for standard practice, and further work would be needed before anyone can do this. For instance, more information is needed to establish cell dosage, the timing of transplantation and how best to measure heart function.

One large trial, called BAMI, is already under way. The European Society of Cardiology for Stem Cells and Cardiac Repair is conducting the trial, which is funded by the European Union Seventh Framework Programme for Research and Innovation (EU FP7-BAMI).

Anthony Mathur, a co-author of this latest Cochrane review, and principal investigator of the BAMI trial, 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."

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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Read this article:
Bone Marrow Stem Cells Help Heal Heart Attack Damage

WHEN a piece of muscle in a person's heart dies from lack of blood flow, it scars over and is lost.

But a team of researchers from the Cedars Sinai Heart Institute in Los Angeles has proven that those muscles may not necessarily be gone forever.

In a study that may change how heart attacks are treated, Eduardo Marban and his team used stem cells to re-grow damaged heart muscle. In the 17 patients who received the therapy, Mr Marban measured an average 50 per cent reduction in the size of the scar tissue.

"One of the holy grails in medicine has been the use of medicine to achieve regeneration," he said. "Patients that were treated not only experienced shrinkage of their scars, but also new growth of their heart muscle, which is very exciting."

The stem cells were not derived from embryos, but instead were developed from the patients' own hearts. Mr Marban's team inserted a catheter into the diseased hearts and took a small biopsy of muscle. In the laboratory, the tissue was manipulated into producing stem cells to re-inject into the patients' hearts.

Over the course of a year, the cells took root in cardiac tissue, encouraging the heart to create new muscle and blood vessels. In other words, the heart actually began to mend itself.

While similar research has been done using stem cells from bone marrow, this is the first time that stem cells derived from a patient's own cardiac tissue have been used.

Mr Marban believes this therapy could be broadly used in many of the five to seven million Americans who suffer from heart disease every year. And he said the applications could go well beyond diseased hearts.

"If we can do that in the heart, I don't see any reason, conceptually, why we couldn't do it in kidneys for example, or pancreas or other organs that have very limited regenerative capacity," he said.

While the procedure may be a revolutionary medical technique, there are still a few more puzzling questions about the research that Mr Marban would like to investigate further.

For example, while the patients grew new heart muscle and saw a dramatic reduction in scar tissue, the actual function of their hearts did not show a significant improvement. And it appeared the stem cells themselves may not have turned into cardiac muscle, but rather they stimulated the heart to produce new muscle cells.

Nonetheless, the potential success of this research could hold a lot of promise for the millions of Americans who suffer from heart disease each and every year, which is the leading cause of death in the United States.

If his future experiments yield the same results as this initial study, Mr Marban said he could be offering this therapy to patients within four years - and that could go a long way in mending all of America's broken hearts.

Read more here.

Link:
Stem cells could fix broken hearts

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

See more here:
Scarred Hearts Can Be Mended With Stem Cell Therapy

Click here to listen to this podcast

Valentine's Day can lead to plenty of broken hearts. But for cardiac wounds that time alone won't heal, science has made some major advances. When it comes to heart attack, for example, a big development is emerging from a tiny source. Stem cells are coming of age. 

Stem cells, harvested from a patient's own bone marrow, have been heralded as a potential quick fix for damaged heart tissue. But can these progenitor cells actually work to heal massive muscle damage?

A new review of 33 studies assessed data from more than 1,700 heart attack patients. The review researchers found that those patients treated with stem cells—in addition to the standard care of angioplasty—had stronger tickers for years to come than those who had not gotten stem cell therapy. The review article is published in The Cochrane Library. [David Clifford et al., Stem Cell Treatment for Acute Myocardial Infarction, link to come]

It's too early to say whether those with stem cell treatments will live longer, according to the new analysis. But for affairs of the heart, it's more evidence that good things can come in very small packages.

—Katherine Harmon

[The above text is a transcript of this podcast]  
 

Follow Scientific American on Twitter @SciAm and @SciamBlogs. Visit ScientificAmerican.com for the latest in science, health and technology news.
© 2012 ScientificAmerican.com. All rights reserved.

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Stem Cells Help Heal Broken Hearts

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."

Read more:
Stem Cells May Help Regenerate Heart Muscle

Home > News > health-news

Washington, Feb 14 : 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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Radiation therapy transforms breast cancer cells into cancer stem cells

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

Here is the original post:
Stem Cells Could Help Heal Broken Hearts [Medicine]

The damage caused by a heart attack was healed by using stem cells gathered from the patient’s own heart in a small trial written up in The Lancet journal, according to the BBC.

The preliminary study was carried out at the Cedars-Sinai Heart Institute in Los Angeles and Johns Hopkins University in Baltimore, and involved 25 patients who had suffered heart attacks recently, reported The Los Angeles Times.

Seventeen of the subjects in the study were given infusions of stem cells “cultured from a raisin-sized chunk of their own heart tissue,” while the other eight were given standard care, reported The LA Times.

The size of the scars on heart tissue damaged by a heart attack decreased in size from 24 percent of the heart to 12 percent of the heart, said Dr. Eduardo Márban, the lead researcher in the study. He wrote to The LA Times in an email that the most surprising aspect of the findings was the fact that the heart could regrow healthy tissue.

More on GlobalPost: Global malaria deaths twice as high as estimated, Lancet study says

The study used a procedure invented by Márban to isolate heart stem cells from healthy tissue from each patient’s heart, and then grow millions of new cells in a petri dish, according to CNN. The patients who received the stem cell treatment either had 12 million or 25 million such cells injected back into their hearts.

Deepak Shrivastava, the director of the Gladstone Institute of Cariovascular Disease based in San Francisco, told Bloomberg, “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.”

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

More on GlobalPost: Study links high calorie intake with memory loss

http://www.globalpost.com/dispatch/news/health/120213/stem-cells-used-heal-heart-attack-damage

Continued here:
Stem cells used to heal heart attack damage

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.

The rest is here:
Cardiac stem cells can restore heart muscles, says study