Study finds regenerating heart in small fish may eventually point way for new heart therapy

Thursday, December 12th 2002, 12:00 am

By: News On 6

WASHINGTON (AP) _ In a step toward finding ways to help ailing human hearts repair themselves, researchers have shown that the tiny zebrafish is able to totally regenerate cardiac muscle and fully recover after about 20 percent of its heart has been surgically removed.

Scientists said the work boosts efforts by many researchers to find ways to grow new, healthy cells to replace scarred heart tissue in cardiac patients, a goal still many years away.

Most researchers are attempting to grow new heart cells by manipulating stem cells to prompt them to transform into cardiac tissue.

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

Once the genes are found in zebrafish, said Keating, ``it is likely that there are corresponding genes in the human genome.''

``Is it possible that this could lead to human cardiac regeneration?'' he asked. ``The answer is yes, it could.''

Keating, a Howard Hughes Medical Institute researcher at Harvard Medical School, chose the zebrafish, a much-studied laboratory animal. It was known that the one-inch long, black-and-white striped fish could regenerate fins and eye parts, but nobody had ever tested to see if the little swimmer could grow new heart cells.

In the study, the researchers anesthetized the animals and then quickly cut into their abdomen to scissor away about 20 percent of their two-chambered heart. The incision was blotted, to stop bleeding, and the fish was returned to the water. Eight out of 10 of the test animals survived the radical procedure, said Keating.

``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,'' said Keating. ``We have looked microscopically at the heart and it is beating and all aspects of it seem to be contracting.''

This is in marked contrast 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,'' said Keating. Instead, injured cells are replaced by scar tissue which does not contract like muscle or conduct the electrical impulses needed for a normal heart beat.

Keating said the next step in his studies will be to start identifying the genes that the little zebrafish uses to grow new heart muscle cells.

``There's probably a whole family of genes involved,'' he said.

Dr. Joshua M. Hare, a researcher at the Johns Hopkins University School of Medicine who is attempting to regenerate human heart tissue using stem cells, said the work by Keating and his team ``is definitely promising.''

Finding the self-repair genes of the zebrafish, he said, ``will provide very valuable clues into the reasons that human hearts don't fully regenerate or find ways to stimulate the human heart to regenerate.''

John Fakunding, head of a heart research program at the National Heart Lung and Blood Institute, one of the National Institutes of Medicine, said Keating has now created a laboratory model that may be used to learn how to grow new heart tissue in humans.

``There is a lot of focus on repairing the heart using regenerative medicine, or growing new cells,'' said Fakunding. Most researchers are using stem cells, but Keating's approach addresses the problem on a more basic, genetic level and is looking at how to cause the heart to grow healthy muscle instead of scar tissue, he said.

``It may eventually be very applicable to humans and become a treatment for damaged hearts,'' said Fakunding.