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"This is one of the largest series of stem cell-treated patients reported so far and perhaps the first to inject stem cells directly into the heart," says senior author James T. Willerson, M.D., president of the University of Texas Health Science Center at Houston and medical director and chief of cardiology at the Texas Heart Institute. "If our findings are confirmed in larger trials, this procedure could lead to an effective treatment for severe heart failure, and perhaps to a new form of gene therapy."
The innovative study involving 21 Brazilian patients was conducted by researchers from the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston, and the Hospital Procardiaco and the Federal University, both in Rio de Janeiro. Emerson C. Perin, M.D., Ph.D., and Hans F. R. Dohmann, M.D., led the Brazilian site investigations.
Heart failure is the inability of damaged heart muscle to pump enough blood to serve the body's needs. About 550,000 new cases of heart failure are diagnosed each year in the United States, according to the American Heart Association. The disease caused about 51,500 deaths in the year 2000.
Stem cells are at an early stage of maturation and can become specific types of cells, such as heart muscle. Willerson and his colleagues began investigating their use as a potential treatment for heart failure about eight years ago.
"We reached the point in our studies where we were certain that, in animals, stem cell transplants were safe and improved the function of the heart and its blood flow," Willerson says.
After receiving approval from the Hospital Procardiaco ethics committee and the Brazilian National Research Ethics Council, the researchers began the trial in end-stage patients.
"These patients were desperately ill," Willerson says. "They had a relatively high risk of dying, and had no other forms of therapy available because their heart failure was so severe."
Fourteen patients received an average of 15 injections containing about two million stem cells each. Seven other patients served as a comparison, or control group. Both groups received the same medical care and monitoring.
The treated patients received a type of stem cell called a bone marrow mononuclear cell, drawn from their bone marrow about four hours before their procedure. These cells carry a "marker" protein on their surface called CD34, which enabled the researchers to identify them.
Researchers chose the cells bearing CD34 because they are believed to have a high probability of becoming blood-vessel cells.
The procedure involved threading a catheter through an artery, into the left ventricle (the heart's main pumping chamber), and "mapping" specific sites of muscle damage. Then stem cells were injected into these areas.
After two months, the treated patients had significantly less heart failure and angina, and were more able to pump blood than the untreated patients. The treated group also tended to do better on treadmill tests. At four months, the treated patients had a sustained improvement in pumping power and ability to supply blood to the body.
The reason for such improvement remains uncertain. "Either these stem cells became new blood vessel and new heart muscle cells, or their presence stimulated the development of one or both," Willerson suggests.
None of the treated patients had serious problems such as sustained irregular heart rhythms, heart attack or death during or soon after the procedure. All patients went home after three days.
Two patients died during the follow-up period. A control patient died two weeks after entering the study, and a treated patient died 14 weeks into the trials. Their families refused permission for autopsies to determine the causes of death.
"We studied a small number of patients, and we will need to study a much larger number in many medical centers to identify the benefits and risks that might exist," says Willerson.
The researchers plan to expand the trial in Brazil, and to begin studying the experimental procedure in Houston soon. They also plan to look for other types of adult stem cells that might prove beneficial in heart failure.
"And then we plan to use these stem cells as a carrier to deliver new genes to failing hearts," Willerson says. "We are working on that in the laboratory."
Other co-authors are Radovan Borojevic, Ph.D.; Suzana A. Silva, M.D.; Andre L. S. Sousa, M.D.; Claudio T. Mesquita, M.D., Ph.D.; Maria I. D. Rossi, Ph.D.; Antonio C. Carvalho, M.D., Ph.D.; Helio S. Dutra, Ph.D.; Hans J. F. Dohmann, M.D., Ph.D.; Guilherme V. Silva, M. D.; Luciano Belém, M.D.; Ricardo Vivacqua, M.D.; Fernando O. D. Rangel, M.D.; Roberto Esporcatte, M.D.; Yong J. Geng, M.D., Ph.D.; William K. Vaughn, Ph.D.; Joao A. R. Assad, M.D.; and Evandro T. Mesquita, M.D., Ph.D.
NR03 - 1055 (Circ/Willerson)
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