Scarred Hearts Healed After Heart Attack

Heart-Attack Damage Heals After Stem Cell Treatment

Feb. 13, 2012 -- A new stem cell treatment resurrects dead, scarred heart muscle damaged by a recent heart attack.

The finding, just in time for Valentine's Day, is the clearest evidence yet that literally broken hearts can heal. All that's 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, tells 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, director of the Cedars-Sinai Heart Institute in Los Angeles, led the study. He invented the "cardiosphere" culture technique used to create the stem cells and founded the company developing the treatment.

It's the first completed, controlled clinical trial showing that scarred heart tissue can be repaired. Earlier work in patients with heart failure, using different stem cells or bone-marrow stem cells, also showed that the heart can regenerate itself.

"These findings suggest that this therapeutic approach is feasible and has the potential to provide a treatment strategy for cardiac regeneration after [heart attack]," write University of Hong Kong researchers Chung-Wah Siu and Hung-Fat Tse. Their editorial accompanies the Marban report in the Feb. 14 advance online issue of The Lancet.

Heart Regenerates With Stem Cell Help

The stem cells don't do what people think they do, Marban says.

It's been thought that the stem cells multiply over and over again. In time, they were supposed to be turning themselves and their daughter cells into new, working heart muscle.

But the stem cells seem to be doing something much more amazing.

"For reasons we didn't initially know, they stimulate the heart to fix itself," Marban says. "The repair is from the heart itself and not from the cells we give them."

Exactly how the stem cells do this is a matter of "feverish research" in Marban's lab.

The phase I clinical trial enrolled 25 patients who had just had a heart attack. On average, each patient had lost a quarter of his heart muscle. MRI scans showed massive scars.

Eight patients got standard care. The other 17 received increasing infusions of what Marban calls stem cells. The cells were grown in the lab from tiny amounts of heart cells taken from the patients' own hearts via biopsy. Six to 12 weeks later, the cells were infused directly back into patients' hearts.

A year later, the mass of scar tissue in the treated patients' hearts got 42% smaller. And healthy heart muscle increased by 60%. No such regeneration was seen in the patients who got standard care.

Because all of the patients were doing relatively well, there was no dramatic difference in clinical outcome. However, treated patients had a bit better exercise endurance.

"This discovery challenges the conventional wisdom that, once established, cardiac scarring is permanent and that, once lost, healthy heart muscle cannot be restored," Marban and colleagues conclude.

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Scarred Hearts Healed After Heart Attack

Scarred Hearts Can Be Mended With Novel Stem Cell Therapy, Study Finds

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 (43935MF) 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, Lisa Marban, is also a founder and chief executive officer.

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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Scarred Hearts Can Be Mended With Novel Stem Cell Therapy, Study Finds

First-of-its-kind stem cell study re-grows healthy heart muscle in heart attack patients

Public release date: 13-Feb-2012
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Contact: Sally Stewart
sally.stewart@cshs.org
310-248-6566
Cedars-Sinai Medical Center

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 muscle.

Patients who underwent the stem cell procedure demonstrated a significant reduction in the size of the scar left on the heart muscle by a heart attack. Patients also experienced a sizable increase in healthy heart muscle following the experimental stem cell treatments.

One year after receiving the stem cell treatment, scar size was reduced from 24 percent to 12 percent of the heart in patients treated with cells (an average drop of about 50 percent). Patients in the control group, who did not receive stem cells, did not experience a reduction in their heart attack scars.

The study appears online at http://www.thelancet.com and will be in a future issue of the journal's print edition.

"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," said Eduardo Marb?n, MD, PhD, the director of the Cedars-Sinai Heart Institute who invented the procedures and technology involved in the study. "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."

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

As an initial part of the study, in 2009, Marb?n and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and re-grow healthy muscle in a heart that had been injured by a heart attack.

The 25 patients -- average age of 53 -- who participated in this completed study experienced heart attacks 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 wrought by the heart attack. Patients were treated at Cedars-Sinai Heart Institute and at Johns Hopkins Hospital in Baltimore.

Eight patients served as controls in the study, receiving conventional medical care for heart attack survivors, including prescription medicine, exercise recommendations and dietary advice.

The other 17 patients who were randomized to receive the stem cells underwent a minimally invasive biopsy, under local anesthesia. Using a catheter inserted through a vein in the patient's neck, doctors removed small pieces of heart tissue, about half the size of a raisin. The biopsied heart tissue was then taken to Marb?n's specialized lab at Cedars-Sinai, using methods he invented to culture and multiply the cells.

In the third and final step, the now-multiplied heart-derived cells ? approximately 12 million to 25 million ? were reintroduced into the patient's coronary arteries during a second, minimally invasive [catheter] procedure.

Patients who received stem cell treatment experienced an average of 50 percent reduction in their heart attack scars 12 months after infusion while patients who received standard medical management did not experience shrinkage in the damaged tissue.

"This discovery challenges the conventional wisdom that, once established, scar is permanent and that, once lost, healthy heart muscle cannot be restored," said Marb?n, The Mark S. Siegel Family Professor.

The process to grow cardiac-derived stem cells involved in the study was developed earlier by Marb?n when he was on the faculty of Johns Hopkins University. The university has filed for a patent on that intellectual property and has licensed it to a company in which Dr. Marb?n has a financial interest. 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.

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About the Cedars-Sinai Heart Institute

The Cedars-Sinai Heart Institute is internationally recognized for outstanding heart care built on decades of innovation and leading-edge research. From cardiac imaging and advanced diagnostics to surgical repair of complex heart problems to the training of the heart specialists of tomorrow and research that is deepening medical knowledge and practice, the Cedars-Sinai Heart Institute is known around the world for excellence and innovations.

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First-of-its-kind stem cell study re-grows healthy heart muscle in heart attack patients

Stem Cell Treatment Might Reverse Heart Attack Damage

MONDAY, Feb. 13 (HealthDay News) -- Stem cell therapy's promise for healing damaged tissues may have gotten a bit closer to reality. In a small, early study, heart damage was reversed in heart-attack patients treated with their own cardiac stem cells, researchers report.

The cells, called cardiosphere-derived stem cells, regrew damaged heart muscle and reversed scarring one year later, the authors say.

Up until now, heart specialists' best tool to help minimize damage following a heart attack has been to surgically clear blocked arteries.

"In our treatment, we dissolved scar and replaced it with living heart muscle. Such 'therapeutic regeneration' has long been the holy grail of cell therapy, but had never been accomplished before; we now seem to have done it," said study author Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles.

However, outside experts cautioned that the findings are preliminary and the treatment is far from ready for widespread use among heart-attack survivors.

The study, published online Feb. 14 in The Lancet, involved 25 middle-aged patients (average age 53) who had suffered a heart attack. Seventeen underwent stem cell infusions while eight received standard post-heart attack care, including medication and exercise therapy.

The stem cells were obtained using a minimally invasive procedure, according to the researchers from Cedars-Sinai and the Johns Hopkins Hospital in Baltimore.

Patients received a local anesthetic and then a catheter was threaded through a neck vein down to the heart, where a tiny portion of muscle was taken. The sample provided all the researchers needed to generate a supply of new stem cells -- 12 million to 25 million -- that were then transplanted back into the heart-attack patient during a second minimally invasive procedure.

One year after the procedure, the infusion patients' cardiac scar sizes had shrunk by about half. Scar size was reduced from 24 percent to 12 percent of the heart, the team said. In contrast, the patients receiving standard care experienced no scar shrinkage.

Initial muscle damage and healed tissue were measured using MRI scans.

After six months, four patients in the stem-cell group experienced serious adverse events compared with only one patient in the control group. At one year, two more stem-cell patients had a serious complication. However, only one such event -- a heart attack -- might have been related to the treatment, according to the study.

In a news release, Marban said that "the effects are substantial and surprisingly larger in humans than they were in animal tests."

Other experts were cautiously optimistic. Cardiac expert Dr. Bernard Gersh, a professor of medicine at Mayo Clinic, is not affiliated with the research but is familiar with the findings.

"This study demonstrates that it is safe and feasible to administer these cardiac-derived stem cells and the results are interesting and encouraging," he said.

Another specialist said that while provocative and promising, the findings remain early, phase-one research. "It's a proof-of-concept study," said interventional cardiologist Dr. Thomas Povsic, an assistant professor of medicine at the Duke Clinical Research Institute, in Durham, N.C.

And Dr. Chip Lavie, medical director of Cardiac Rehabilitation and Prevention at the John Ochsner Heart and Vascular Institute, in New Orleans, also discussed the results. He said that while the study showed that the cardiac stem cells reduced scar tissue and increased the area of live heart tissue in heart attack patients with moderately damaged overall heart tissue, it did not demonstrate a reduction in heart size or any improvement in the heart's pumping ability.

"It did not improve the ejection fraction, which is a very important measurement used to define the overall heart's pumping ability," Lavie noted. "Certainly, much larger studies of various types of heart attack patients will be needed before this even comes close to being a viable potential therapy for the large number of heart attack initial survivors."

Povsic concurred that much larger studies are needed. "The next step is showing it really helps patients in some kind of meaningful way, by either preventing death, healing them or making them feel better."

It's unclear what the cost will be, Povsic added. "What society is going to be willing to pay for this is going to be based on how much good it ends up doing. If they truly regenerate a heart and prevent a heart transplant, that would save a lot money."

Marban, who invented the stem cell treatment, said the while it would not replace bypass surgery or angioplasty, "it might be useful in treating 'irreversible' injury that may persist after those procedures."

As a rough estimate, he said that if larger, phase 2 trials were successful, the treatment might be available to the general public by about 2016.

More information

The U.S. National Heart, Lung, and Blood Institute describes current heart attack treatment.

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Stem Cell Treatment Might Reverse Heart Attack Damage

Vet offers stem cell therapy for dogs

COLUMBIA, SC (WIS) - Cutting-edge arthritis treatment for our four-legged family members is now available in Columbia.

Banks Animal Hospital is the first in the area to offer in-house Stem Cell therapy. It uses your pets own body to heal itself.

Take 13-year-old Maggie, for example. The energetic pup has a limp that usually keeps her from jumping or going up stairs.

"Today when everybody's out there filming her little limp it's not as pronounced because she wants to please," said Maggie's owner, Beth Phibbs. "She's just a great dog."

But a great attitude wasn't enough to repair a bad case of cervical spine arthritis.

So Monday, Beth brought Maggie to Banks Animal Hospital for the Stem Cell therapy. Like many, Beth had never heard of Stem Cell work in animals. "Until Dr. Banks mentioned it to me I was like, beg your pardon?"

"There's no down side, no side effects because you're using your own cells," said Dr Ken Banks.

Banks and his staff first gather some of Maggie's blood and fat. Both are good places to find the repair cells they're after. Adult stem cells, not the controversial embryonic kind, are then separated and spun down.

"The repair system in Maggie's body has failed," said Jason Richardson of MediVet-America. "It's fallen asleep at the wheel, we're taking these repair cells, activating them so a chronic condition like osteo arthritis to Maggie will now be an acute illness."

This kind of treatment used to take days with material being shipped across the country, but now it can be done in hours.

"The ability to do it same day, convenience, the ability to do it in clinic saves a lot of money to the doctor which he can then pass on to the patient," said Richardson.

The treatment will still run you around $2,000, but Richardson says that's half of what the similar treatment use to cost.

When it's over, Maggie should be able to live out her life pain and drug free -- something Phibbs is looking forward to.

"I'm hoping in a couple of weeks she's gonna have a new lease on life," said Phibbs.

Copyright 2012 WIS. All rights reserved.

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Vet offers stem cell therapy for dogs

Radiation treatment transforms breast cancer cells into cancer stem cells

Public release date: 13-Feb-2012
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles Health Sciences

Breast cancer stem cells are thought to be the sole source of tumor recurrence and are known to be resistant to radiation therapy and don't respond well to chemotherapy.

Now, researchers with the UCLA Department of Radiation Oncology at UCLA's Jonsson Comprehensive Cancer Center report for the first time that radiation treatment ?despite killing half of all tumor cells during every treatment - transforms other cancer cells into treatment-resistant breast cancer stem cells.

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."

The study appears DATE in the early online edition of the peer-reviewed journal Stem Cells.

"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 states.

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 tumor.

"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."

###

This study was funded by the National Cancer Institute, the California Breast Cancer Research Program and the Department of Defense. UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

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Radiation treatment transforms breast cancer cells into cancer stem cells