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Research tries to plant new heart cells

24 to take part at Hub hospital

Cardiologists in Boston are using stem cells in an attempt to sprout new blood vessels deep inside patients' hearts, placing the researchers at the vanguard of scientists around the world who are harnessing patients' own bodies to fix their ailing hearts.

The investigators announced yesterday that Edward Gibbons had become the first participant in the experiment at Caritas St. Elizabeth's Medical Center in Brighton, where last month doctors began harvesting stem cells from patients, purifying them, and reinjecting the cells directly into the heart.

Gibbons is one of the millions of Americans with coronary artery disease whose conditions persist and worsen despite repeated operations and other treatments, making them virtual prisoners in their own homes. Every time Gibbons drags his beloved Labrador retriever Brandy 30 feet to the backyard of his Hull house, his chest heaves, and his heart twinges as angina sets in.

If the technique works -- and there's no guarantee it will -- it could revolutionize heart treatment, helping patients avoid painful, perilous bypass surgery and even heart transplants. Because the procedure uses adult stem cells, it is not fraught with the ethical and medical issues that have stalled research using embryonic stem cells. Both types are immature cells capable of growing into blood cells, tissue, and organs.

"This has real promise for a disease that affects 6 million people," said Dr. Roberto Bolli, a nationally recognized cardiology researcher at the University of Louisville. "This is a very serious and very grim condition for which we have not had much to offer our patients."

Still, while cardiac and stem cell specialists hailed the study at St. Elizabeth's, they cautioned that stem cell studies in general have been pocked by failure as much as triumph, even as the field continues to be regarded as a promising avenue of biomedical research.

Doctors are optimistic about the use of stem cells to repair the heart in part because of successful studies in animals at St. Elizabeth's and research on human heart attack patients in Germany, which showed that patients' hearts pumped somewhat better after injections of stem cells.

Even modest success could have significant implications: Heart disease kills more Americans than any other medical condition, and 61 million live with complications from it, about 10 percent of them suffering major disability.

"This is a hot topic; everybody in cardiology is talking about it," said Dr. Yerem Yeghiazarians, director of the cardiac stem cell program at the University of California at San Francisco. "But there's a caveat, that while the preliminary results appear to be promising, a lot more work needs to be done to understand how this might work."

More broadly, the experiment being conducted at St. Elizabeth's is evidence of a dramatic shift in how cardiologists view the heart and its ability to regenerate.

"It really is a revolution in thinking," said Dr. Richard Lee, a cardiologist at Brigham and Women's Hospital in Boston who studies heart failure. "Five years ago, we used to think when heart tissue dies, it's dead. Now, we don't think that anymore."

During the last decade, cardiologists at St. Elizabeth's have been studying whether they could use stem cells to make damaged hearts work better, using grants from the National Institutes of Health. They started with mice and progressed to pigs before considering the approach in humans who have exhausted all other surgical and drug options.

Those patients frequently have endured repeated attempts to use tiny balloons or stainless steel stents to open arteries clogged by plaque, only to have their chest pain return.

Often, that's because the problem isn't in the big vessels most susceptible to treatment. Instead, it's in the tributaries that feed into the larger rivers. And those capillaries aren't easily reached with the tools that surgeons use.

Some of the patients could be candidates for heart transplants, but the need vastly exceeds supply, leaving most hearts destined for the young rather than older patients such as Gibbons, who is 75.

So cardiologists have been hunting for a way to help the heart heal itself.

As research into stem cells has progressed, scientists discovered that these cells in the bone marrow and blood of adults retain the ability to turn into any kind of tissue, including heart muscle and capillaries. The destiny of a particular stem cell is often determined by the neighborhood it calls home. As the immature adult cells mature, they migrate to different parts of the body, including blood-starved tissue in the heart of sick patients.

"Their decision about what to become when they grow up is very context-driven," said Dr. Douglas W. Losordo, chief of cardiology at St. Elizabeth's. "You put them into tissue that lacks blood supply, and they're getting these cues from the environment saying, `Help, we need blood supply,' and they form blood vessels. If you take those cells and put them into another setting, they could become a skin cell."

To test the theory that stem cells collected from heart patients can spawn new blood vessels, the St. Elizabeth's team is conducting a study with 24 participants during the next nine months. To determine whether the approach really works, the scientists have adopted the gold standard of biomedical research: 18 patients will get the actual stem cell treatment while six will receive an injected placebo.

Rather than harvest the cells directly from bone marrow, an often painful approach, the researchers are using medication to coax the cells from the marrow into the blood. Then, an array of different stem cells are separated from the blood.

The researchers further cull the cells by using magnets to select those cells most likely to grow blood vessels in the heart.

Doctors thread a catheter through the groin and eventually to the heart to deliver the cells. To enhance prospects that they seed the cells where the need is greatest and success most probable, they use a three-dimensional imaging system originally invented to guide military missiles and later adapted for medical purposes by Israeli researchers.

"You talk about beating swords into plowshares," Losordo said.

The St. Elizabeth's scientists expect that it will take two weeks to four weeks for new blood supply to be generated in the hearts of patients and one month to two months before symptoms of conditions such as angina abate.

Cardiologists not involved with the experiment said they expect no significant complications from the technique, but earlier research involving muscle cells injected into the heart resulted in problems with heart rhythm in some patients. Specialists said they do not anticipate a comparable complication from stem cells, but to make sure, the St. Elizabeth's doctors are having participants in the study wear a vest that measures their heart beat and can restore a normal rhythm if necessary.

"For this population of patients, I have less reservation doing this sort of experimental procedure, because after all we don't have much else to offer them," said Dr. Victor Dzau, a cardiologist and chief of the Department of Medicine at Brigham and Women's Hospital.

Gibbons, known to family and friends as "Bob," was such a patient. First diagnosed with angina in 1983, he underwent double heart bypass surgery in 2000 as well as other procedures to open clogged arteries. But the symptoms kept returning.

In the past year and a half, he has spent most days at home, feeling as though his heart and chest are clamped in a vise. When he heard about the St. Elizabeth's stem cell study, he had no hesitation, even though he knew there was no certainty he would be among the participants to get the cells, rather than a placebo. He and the researchers won't know whether he got the stem cells until the study is completed.

"The only alternative left to try was this," Gibbons said. "This will be a godsend if those little old seeds start to sprout."

Stephen Smith can be reached at stsmith@globe.com.

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