Gender Study Suggests Heart Can Repair Itself

VALHALLA, N.Y.- A novel study of what happens to female hearts transplanted into male patients offers compelling new evidence that the heart can repair itself, a potential boon for millions of patients.

The findings challenge long-held assumptions that the heart can't replace muscle tissue that is lost as a result of a heart attack or other malady. It also raises the possibility that the body's own regenerative powers might someday be used as a treatment for heart patients.

"We are trying to see how we can utilize what is present in the heart and mobilize it to repair damage and restore function," says Piero Anversa, director of the Cardiovascular Research Institute at New York Medical College and principal investigator of the study. The paper, published in today's New England Journal of Medicine, is the latest in a series of recent reports by Dr. Anversa and his colleagues that describe how the heart can replace its component cells.

Studying female hearts transplanted into male patients offers a clever avenue of investigation, because male cells have Y chromosomes and are distinguishable from female cells that don't. Dr Anversa studied tissue from eight deceased men who had received female donor hearts. In several analyses, he and his research team found strong evidence that cells from the recipients' bodies had migrated to form new tissue in the transplanted hearts. The cells had characteristics of stem cells, meaning they initially had no specific function, but grew to form new muscle and blood-vessel tissue.

The migration of the male cells happened quickly. In one patient who died four days after transplant, cells from the recipient had already fully integrated with cells from the donor heart, the researchers found. All told, Y-chromosome cells were identified in 14% to 20% of new muscle and blood-vessel growth in the donated heart.

The data show conclusively that the heart "has the capacity for self-renewal," Roberto Bolli, a researcher at the University of Louisville in Kentucky, says in an editorial accompanying the new study.

A number of questions remain unanswered, including where the migrating cells originate. One theory is that they develop in bone marrow, the source of the body's blood cells. Dr Anversa says his team found primitive cells in both the donor heart and the host, as well as in the hearts of 10 control patients who didn't receive transplants, Dr. Anversa believes that indicates the heart has its own stem cells on site , which, if true, could make a particularly attractive approach for treatment.

Another question is whether the new growth of tissue actually leads to improvement in function of the heart - something not possible to determine in looking at tissue obtained at autopsy.

"The problem is to understand how we activate and mobilize the cells and make them go to the areas of damage and create a new, healthy functioning organism, "Dr. Anversa says. His laboratory, funded by the National Institutes of Health, is moving forward with new experiments intended to determine that.

About five million Americans suffer from heart failure, a debilitating condition where the heart gradually loses its ability to pump blood, and an additional 500,000 are diagnosed with it each year. The leading cause is heart attack, which deprives heart muscle of oxygen, leaving dead scar tissue in the affected areas. As a rule, new heart cells don't grow over scar tissue - one reason why many heart researchers have long believed that the heart doesn't replace lost muscle and other cells.

Other researchers, including groups in France and the U.S., are taking a different approach to heart-muscle regeneration. They are harvesting muscle stem cells from elsewhere in the body, causing them to grow in the laboratory and then injecting them directly into the heart muscle in hopes of spurring heart-cell growth.

Mark Pfeffer, a cardiologist at Harvard Medical school and Brigham and Women's Hospital, Boston, who is familiar with Dr. Anversa's work, says the new report, in combination with his previous research, is likely to open up a new area of innovation. If the findings become widely accepted, scientists will race to find ways to capitalize on the hearts' self-healing ability.

"If this inherent capacity to heal is there, it's obviously not adequate [alone], "Dr. Pfeffer says. "Otherwise we wouldn't have people who have had a heart attack go into heart failure."