Risks Found in Stem Cell Therapy for Heart

Studies find complications in humans and dogs

THURSDAY, March 4, 2004 (HealthDayNews) -- Two new trials send a warning note about the use of stem cells to repair heart damage.

Cardiologists at Seoul National University in South Korea say they halted a trial in which heart attack patients were given infusions of their own stem cells because many of the heart arteries opened by the treatment unexpectedly began to close again.

And animal researchers at the University of California at Davis say they stopped similar trials in dogs when they detected a high incidence of tiny pockets of cell death called microinfarcts. The formal medical name of a heart attack is a myocardial infarction, which is heart cell death on a large scale.

Both studies appear in the March 6 issue of The Lancet.

The idea of using stem cells, which have the capability of transforming themselves into healthy, mature cells, has excited interest in a number of medical fields, including cardiology.

The U. S. Food and Drug Administration has essentially stopped human trials of heart stem cell therapy in this country, citing safety concerns and the need for more animal studies.

"We're one of the few groups using stem cells in animals with the intent of applying stem cell technology to human patients," says Dr. P. Richard Vulliet, a professor of veterinary pharmacology and therapeutics at the University of California Davis School of Veterinary Medicine. "We essentially took protocols similar to what is being used in humans and did them in normal dogs."

The disease-free dogs were anesthetized, and stem cells taken from their bone marrow were infused into their coronary arteries.

When those cells entered the tiniest blood vessels of the heart, they somehow caused microinfarcts, Vulliet says.

"Because we were working with normal, healthy dogs, this was a surprising finding," he says. "We were giving one dose of stem cells, in the range of what is being done in humans."

The results will be presented at a meeting on stem cell therapy being held in Washington, D.C., later this month by the FDA, Vulliet says.

"We are continuing with these studies at a lower dose," he says. "We believe that the dose we gave was too high, although it was similar to those that have been reported in humans."

The Korean results must be looked at carefully for several reasons, says Dr. Cindy Grines, director of the cardiac catheterization laboratory at William Beaumont Hospital in Royal Oak, Mich., which has done pioneering work in the field.

"Two things are very odd," Grines says. "First, they didn't enroll many patients [27 in all, including controls]. Then they stopped the trial early."

Most important, the technique used in Seoul was very different from that used in the one trial at heart stem cell treatment at William Beaumont, she says -- a difference that might have helped cause the problem encountered by the Korean physicians.

At William Beaumont, the effort to reopen the clogged artery causing the heart problem is made quickly, in the first hours of treatment, with implantation of a stent, a flexible tube. The plan calls for then waiting several days. If trouble develops, then the stem cell infusion would be tried.

Instead, the Koreans waited more than 48 hours before implanting a stent. When they started stem cell infusions, they also gave the patients granulocyte-colony stimulating factor (G-CSF), a molecule used to encourage stem cell growth.

The G-CSF infusion might have caused increased cell growth that led to narrowing of the blood vessels seen in the patients who got the stem cell treatment, Grines says.

But at this time, the issue of stem cell safety is purely academic in the United States, because of the FDA ruling, she says. Plans were being made for expanded work in six medical centers when the ruling was issued, Grines says.

"They wanted us to go back to testing in animals," she says. "That would have set us back for years, so we abandoned the idea entirely. The work is going on in a number of other countries."

More information

Learn about stem cell therapy for the heart and other conditions at the American Heart Association or the National Institutes of Health.

SOURCES: P. Richard Vulliet, D.V.M., Ph.D., professor, veterinary pharmacology and therapeutics, School of Veterinary Medicine, University of California, Davis; Cindy Grines, M.D., director, cardiac catheterization laboratory, William Beaumont Hospital, Royal Oak, Mich.; March 6, 2004, The Lancet
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