Researchers Coax Hearts to Heal Themselves
发布时间:2011-06-12 浏览次数:

Self-healing? After a heart attack like this patient has suffered, cells in the heart might be able to make new muscle, a mouse study suggests.

Heart attacks kill because they strangle heart muscle, destroying cells and preventing the organ from pumping properly. Now, researchers reveal that they have nudged cells within mouse hearts to repair some of the damage, a discovery that might prompt new treatments for heart attacks in humans.

Researchers are probing several ways to encourage the heart to fix itself. Last year, for instance, cardiac stem cell biologist Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease in San Francisco, California, and colleagues inserted extra copies of three genes into scar tissue cells, triggering them to morph into cardiomyocytes, or heart muscle cells. Another possible approach involves harnessing so-called resident progenitor cells, unspecialized cells within the heart that are similar to stem cells and can mature into cardiomyocytes. The difficulty has been identifying the progenitor cells in adults and determining whether they could yield enough fresh muscle.

Stem cell biologist Paul Riley of University College London and colleagues gauged the capabilities of progenitor cells in the epicardium, the heart's outer layer. During embryonic development, progenitor cells there are a major source of cardiomyocytes. In adults, however, the cells apparently slack off. To recapture the cells' youthful vigor, the researchers injected mice with thymosin β4, a compound already undergoing clinical trials as a heart attack treatment because it helps cardiomyocytes survive and spurs the growth of new blood vessels. The researchers then mimicked a heart attack in the animals by tying off one of the arteries that deliver blood to the heart, injuring part of the muscle.

Unlike control mice that didn't appear to fashion any new cardiomyocytes, animals dosed with thymosin β4 made some of the cells, the team reports online today in Nature. The cells infiltrated the damaged zone left by the simulated heart attack and meshed with other cardiomyocytes physically and electrically, allowing them to beat. They also seemed to prevent some of the damage that can result from a heart attack. Magnetic resonance imaging scans showed that the hearts of mice that had received thymosin β4 had smaller scars and were able to pump more blood with each contraction than were the hearts of untreated rodents. "Having a resident source of cells that might repair muscle and blood vessels is important," Riley says.

Because thymosin β4 wasn't very efficient—less than 1% of the progenitor cells transformed into cardiomyocytes—the researchers are trying to identify other, more potent molecules. Drugs that prod progenitor cells to create new muscle might benefit patients who have suffered heart attacks. But they might work better if patients took the drug preventively, to prime the progenitor cells for action, Riley says. He envisions that people who are susceptible to heart attacks, perhaps because they have high cholesterol and other risk factors, would take regular doses, keeping their progenitor cells in a state of readiness.

The study "provides strong evidence that there is a population of cells from the epicardium that can turn into new muscle," Srivastava says. "The real question is how robust is the process [of cell transformation] and how can it be improved." He recommends that researchers also investigate whether the cells can rebuild cardiac muscle during heart failure, a condition that afflicts some 5 million U.S residents and causes the organ to progressively weaken.