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Adult Stem Cells Help Weakened Hearts

Times Staff Writers

Using stem cells harvested from patients’ own bone marrow, researchers improved cardiac function in heart attack patients months, years -- and even decades -- after the attacks, they reported Wednesday.

The infusion of stem cells boosted cardiac pumping efficiency by 7% in three months -- a modest gain, but still a significant improvement for a chronic condition.

In one case, a patient who had suffered a heart attack 30 years earlier showed an 11% improvement after the treatment, according to the study in the New England Journal of Medicine.

The German researchers also found tentative signs that patients could continue to improve with repeated treatments.

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“We have always thought that a heart attack is permanent damage, but now there is the potential that this damage can be repaired,” said Dr. Christopher P. Cannon, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved in the research.

Though the researchers are uncertain why the therapy works, the findings are a sign that the long-touted regenerative powers of stem cells may be gradually moving from the laboratory into viable human therapies.

Some researchers cautioned that it was too soon to say that the results could be translated into a routine treatment.

“There are a number of therapies that have gotten to this step but when subjected to more rigorous trials have not worked,” said Dr. Gregg C. Fonarow, a professor of cardiovascular medicine at UCLA.

But Dr. Andreas M. Zeiher, chair of the department of medicine at Johann Wolfgang Goethe University in Frankfurt and senior author of the study, said the preliminary results pointed to potential new strategies for treating chronic heart disease, for which there is no cure.

Stem cells present one of the most tantalizing mysteries in medicine. One form, known as embryonic stem cells, are capable of generating any type of tissue in the body, but scientists haven’t learned the biochemical means to transform them.

The current study focused on a second type of cells known as adult stem cells. There are many types, each focused on regenerating a specific group of tissues to help the body repair normal wear and tear.

Stem cells from bone marrow have been used for decades to regenerate blood and immune cells in cancer patients. Laboratory experiments suggest that these cells also can make heart muscle, blood vessels, nerve cells and other tissues.

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The advantage of bone marrow stem cells is that they are easy to extract and can be collected from the same patients they will be used to treat, avoiding problems of tissue rejection.

Heart disease has been one of the primary targets of stem cell research.

One of five deaths in the United States is caused by a heart attack, which occurs when heart muscle is deprived of blood and dies. About 1.2 million heart attacks occur in the United States every year, leading to nearly 500,000 deaths, according to the American Heart Assn.

The German researchers recruited 75 patients who had suffered a heart attack at least three months -- and as long as 30 years -- earlier.

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The patients were already receiving state-of-the-art drug treatments for their heart disease, including the use of beta blockers and cholesterol-lowering statins.

The researchers extracted 50 milliliters of bone marrow from the patients’ hips. They isolated a soup of cells that included the stem cells and infused it into patients within a matter of hours.

The researchers divided the patients into three groups. One received the bone marrow stem cells and another was treated with different stem cells derived from their own blood. A third group served as a control.

Three months later, the researchers tested the patients’ left ventricular ejection fraction, a measure of how much oxygenated blood is pumped into the circulatory system. In healthy people, it ranges from 57% to 75%.

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The patients in the study started out with ejection fractions that averaged from 39% to 43%.

Those treated with bone marrow stem cells saw their heart-pumping efficiency increase over three months by an average of 2.9 points -- a 7% improvement.

Over the same period, patients in the control group saw their pumping efficiency decline by an average of about 3%, and those treated with blood stem cells dropped about 1%.

To confirm their findings, the researchers swapped the treatments and gave patients in the control group either blood or bone marrow stem cells. Again, the patients who got bone marrow cells saw an increase in their pumping efficiency.

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Fonarow of UCLA said the improvement was similar to the effect of statins, which boost pumping efficiency by 5% to 8%.

The patients treated with bone marrow cells showed an increased ability to tolerate physical activity before becoming tired or breathless -- and the improvements have been sustained, Zeiher said.

He said one patient who had suffered a heart attack four years earlier improved by 61% and returned to the golf course to play at least nine holes.

“For the past 20 years, we have obsessed about treating [heart attacks] quickly -- time is muscle,” said Dr. Douglas Losordo, chief of cardiovascular research at St. Elizabeth’s Medical Center in Boston. “What this paper tells us is there is another time window for therapeutic intervention that’s quite a bit longer and larger than we thought.”

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Dr. Anthony Rosenzweig, director of cardiovascular research at Beth Israel Deaconess Medical Center in Boston, said the results suggested the stem cells were doing more than just accelerating the recovery process.

It had been six years on average since these patients had their heart attacks, he said. “If it were just hastening healing after a heart attack, you wouldn’t necessarily predict you’d be able to have a beneficial impact so long after.”

Laboratory experiments have shown the cells can rebuild damaged heart cells, stimulate the formation of new blood vessels and release chemicals that aid the healing process, Zeiher said. Some doctors, however, noted that a key piece of information was missing from the study: What exactly were the bone marrow cells doing inside the heart?

“They provide no evidence that the injected [stem cells] actually settled in the heart,” Dr. Robert S. Schwartz, deputy editor of the New England Journal, wrote in a perspective piece accompanying the study. He added in an interview: “Physicians should know how any therapy they give works. That’s fundamental.”

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Others found the mystery less bothersome.

“We still don’t know how statins work, but I haven’t stopped prescribing them,” Losordo said.

The German researchers also published results of a companion study showing that patients who received bone marrow cells within seven days of a heart attack improved their blood-pumping efficiency by 11% after four months, compared with a 6% boost for patients who got a placebo.

A third study, conducted by researchers in Norway, found their stem cell method provided no improvement, although the study was not precise enough to detect the small increases in pumping efficiency reported by the German team.

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karen.kaplan@latimes.com

alan.zarembo@latimes.com


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