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(Circulation. 2001;103:e9054.)
© 2001 American Heart Association, Inc.
Cardiovascular News
Using Skeletal Muscle Cells to Repair Ailing Hearts
On May 11, 2001, physicians at the University of California at Los Angeles Medical Center transplanted skeletal muscle cells into damaged areas of a Nevada man’s heart in an attempt to repair the damage from repeated myocardial infarctions. The experimental technique took place during coronary artery bypass surgery, but the cells were placed in an area where bypass could not reperfuse the tissue.
The myocytes, which were taken from the patient’s arm, were grown in a laboratory for 10 to 14 days before the surgery. The lab-grown cells were then given back to the patient. These cells are capable of dividing and differentiating into a form that is more similar to cardiac muscle cells than those of the skeleton.
"This procedure is for patients with extensive ischemia and heart failure," said Greg Fonarow, MD, coinvestigator of the project and an assistant professor at the University of California at Los Angeles. Eventually, 4 to 5 centers will be involved in the first phase of testing. Physicians will assess the success of the technique with serial positron emission tomography scans of the affected area. Serial echocardiograms will be used to determine if the cell transplants have improved heart function.
"We are doing extensive safety monitoring," said Dr Fonarow. Concerns about the safety of the technique are theoretical, and there have been no problems in extensive animal trials. The cells are seeded into the heart by injection; they probably divide through 3 to 4 cycles and then remain in place, leaving the area of the heart well seeded. "There is unlikely to be extensive migration of the transplanted cells."
A total of 12 patients will receive the transplants during the trial’s pilot phase, said Dr. Fonarow. The US Food and Drug Administration will carefully scrutinize the results to determine if the studies should continue.
The first few patients will receive transplants of 10 million cells. If that proves safe, then the doses will escalate to 30 million, 100 million, and finally 300 million cells. "We estimate that the transplants will have to be in the 100 to 300 million cell range to have sufficient skeletal muscle cell mass to see a significant improvement in function," said Dr Fonarow.
In the current study, patients who have no areas that can benefit from bypass are not eligible for the cell transplants. The first patient had had 3 previous heart attacks, the most recent only 1 month before surgery. His ejection fraction was only 20% and he suffered from severe cardiovascular disease. The cells were transplanted into the area of greatest damage.
Although Dr Fonarow has already completed the first set of assessments on the patient, he said it is too early to discuss them. "The expectation is that these cells will repair the damaged segment and remain there long-term." If any patient in the study has to undergo a heart transplant, the explanted heart will be carefully studied to determine how the cell transplants worked.
Growing the cells in the laboratory was a tremendous feat, said Dr Fonarow. Diacrin, Inc, of Charlestown, Massachusetts, undertook that part of the procedure. The company’s ability to meet the tight timetable required in these cases "is a critical part of being able to offer" the procedure.
Cleveland Clinic is one of the cooperating centers, as is the University of Pittsburgh School of Medicine. Temple University researchers are planning a similar study that will implant the cells at the same time that they implant a vascular assist device.
Eventually, researchers hope that the cells can be implanted percutaneously, without the need to open the patient’s chest. "I’ve been involved in a lot of different research, but this one has phenomenal potential," said Dr Fonarow.
Human Cardiac Myocytes Divide After Heart Attack
Researchers at New York Medical College in Valhalla reported finding evidence of large-scale replication of heart muscle cells in 2 areas of the heart after a heart attack, a finding that goes against conventional wisdom that such cells do not regenerate (N Engl J Med. 2001;344:1750–1757). "It has long been assumed that when the heart is damaged, such as after a heart attack, heart muscle cells do not regenerate and the damage is permanent," said Claude Lenfant, MD, director of the National Heart, Lung, and Blood Institute, which funded the study. "This assumption has been challenged in recent years by evidence that heart muscle cells may, in fact, regenerate. Now, this latest research provides the most dramatic and clear-cut demonstration to date of heart cell regeneration after cardiac injury."
Piero Anversa, MD, professor of medicine and director of the Cardiovascular Research Institute at New York Medical College, and his colleagues studied cardiac myocytes from the hearts of 13 patients 4 to 12 days after their myocardial infarction and compared them with cells from the hearts of 10 patients who were free of cardiovascular disease.
The samples were taken from the area of the heart close to the attack and from a site more distant from the damaged tissue. Using a high-resolution confocal microscope, Dr Anversa was able to measure the expression of a protein called Ki67, which is found in the nucleus of dividing heart muscle cells and is a strong indicator that cells are dividing.
The researchers also obtained images of mitotic division in the cells and found other evidence of replication, including formation of the mitotic spindle and contractile ring. The evidence was evaluated against a mitotic index, which was a measurement of the degree of myocyte division. In the diseased hearts, the number of heart muscle cells replicating was 70 times higher in the border zone closest to the damaged heart muscles and 24 times higher in the remote area of the heart than in the muscle of normal hearts.
Dr Anversa said he will next attempt to find the source of the dividing heart muscle cells. He theorizes that this division may indicate the existence of cardiac stem cells and, if he can prove that they are real, he can find ways to "make these cells migrate to the region of tissue damage." In doing so, he could improve the repair of damaged heart muscle.
Health and Human Services Officials Correct Comments by Health Care Financing Administration
Officials at the Department of Health and Human Services scrambled to correct comments by Health Care Financing Administration (HCFA) administrator Thomas Scully that indicated the department would be issuing a "scorecard" on physicians, hospitals, and other agencies that provide care to the nation’s elderly. Scully made his comments on Monday, June 4, 2001, before the US Chamber of Commerce. It was his first official presentation.
However, after reports of the statements were printed in the June 5, 2001, issue of the Washington Post, HCFA officials said the agency has no plans to "create a scorecard of ratings," according to the Associated Press. Instead, HCFA is planning to improve the state and private information that the agency collects on nursing homes, dialysis centers, and other healthcare providers. HCFA has "no plans to use the data to release such information," said HCFA spokesman Peter Ashkenaz.
Proponents of giving patients the ability to shop for their own health care have backed efforts to increase the supply of information about providers. However, hospitals, physicians, and other industry groups have vigorously opposed such moves on the grounds that consumers might misinterpret such data.
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