Study regenerates heart in zebrafish

Finding may lead to new cardiac therapy

? A small striped fish common in aquariums and laboratories may lead the way to helping ailing human hearts repair themselves.

A new study shows the zebrafish grows new cells and totally restores its heart after 20 percent of the muscle has been cut away.

Experts said the discovery was an important advance in the new field of “regenerative medicine,” the research effort to learn how to restore diseased organs with healthy, new cells. Most researchers are trying to grow new heart cells by causing stem cells to transform into fresh cardiac tissue.

But a team led by Dr. Mark T. Keating of Harvard University is taking a different approach: The scientists are looking for genetic secrets that enable some animals, such as the zebrafish, to grow new body parts.

Once the regeneration genes are found in zebrafish, he said, “it is likely that there are corresponding genes in the human genome.”

“Is it possible that this could lead to human cardiac regeneration? The answer is yes, it could,” said Keating, the senior author of a study appearing today in the journal Science.

Keating, a Howard Hughes Medical Institute researcher at Harvard Medical School, chose the zebrafish, a much-studied laboratory animal, because it was known that the inchlong fish could regenerate fins and eye parts. But no one had tested to see if it could grow new heart cells.

In the study, the researchers anesthetized the fish and quickly cut into their abdomens to trim about 20 percent of their two-chambered hearts. The incisions were blotted, to stop bleeding, and the fish were returned to the water. Eight of the 10 test animals survived the radical procedure, Keating said.

“They’re not happy for a while,” he said. “They sort of hang out at the bottom of the tank.”

But within 10 days, something remarkable happened: The test fish began swimming normally and soon were as active as their healthy schoolmates.

After two months, Keating said the test fish totally regenerated their hearts, replacing all the lost tissue with new cells that vigorously pumped blood. And, most notably, there was little or no scarring.

“The whole 20 percent of the excised heart regrows and it actually overshoots a little bit,” Keating said. “We have looked microscopically at the heart and it is beating and all aspects of it seem to be contracting.”

This contrasts markedly to what happens in people. A heart attack patient may recover, but the heart is never quite the same.

“There is little or no heart muscle growth following a heart attack in humans,” Keating said. Instead, injured cells are replaced by scar tissue that does not contract like muscle or conduct the electrical impulses needed for a normal heart beat.

Keating said the next step would be to start identifying the genes that zebrafish use to grow new heart muscle cells.