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If Zebrafish Can Regenerate, Why Can't We?

Some animals have the ability to regenerate lost limbs. For humans, regeneration has been limited to the liver and skin. Researchers at the Mount Desert Island Biological Laboratory say the ability to re-grow other human tissue – like the heart – may be more possible than you think especially with their latest discovery.

Dr. Kevin Strange – the president and CEO of the MDI Biological Laboratory – has always been struck by the fact that so many animals can regenerate body parts. It’s made him wonder, ‘why can’t humans?’

“There really is no reason humans can’t do it,” says Strange. “You develop from a single cell embryo. You grow a heart, you grow limbs, you grow a brain, you grow a spinal chord. All the instructions are there for replacing lost and damaged body parts. Why can’t we turn those on in response to an injury?”

A few years ago, Strange had a hunch that it might be possible to develop a drug to turn on those pathways. He and his team had the perfect animal to start exploring that idea. The zebrafish. It’s a common aquarium fish, with a remarkable ability: regrowth of damaged tissue.

Dr. Voot Yin, an assistant professor at the MDI Biological Lab, said, “You name it, damage any tissue and it will grow it right back.”

Also important, says Yin, is this: “The zebrafish has about 70% of the same genes that you and I have.”

Yin led a team of researchers that administered different drugs to zebrafish to try to enhance their ability to regenerate. It was a drug known as MSI-1436 – which was developed from the molecule of a dogfish shark – that yielded a surprising result when tested on the zebrafish’s caudal or tail fin.

“They were actually able to regenerate two-to three-hundred times faster than a placebo,” Yin said.

The caudal fin – a complex tissue made of bones and nerves – not only grew back faster, but it had no overgrowth. That’s just as important. Yin then tested to see whether the drug would have the same effect on a zebrafish heart. It did.

The next step, says Yin, was to test mice, “And what we found was nothing short of a remarkable effect on the heart.”

The injured mammal’s heart regenerated. Heart function improved two to three-fold. Damaged tissue was reduced by about 50%, and there was active proliferation of new heart cells.

“And that, in itself, is kind of the holy grail in cardiac regenerative medicine,” said Yin. “Ultimately, what we want to do is to be able to stimulate new muscle formation, to replace the dying tissue, so that the heart will ultimately recover lost heart function.”

This is a potential game-changer for heart attack patient says Yin. If a damaged heart can repair itself, it could mean the difference between being able to go for a run versus being tied to an oxygen tank.

Dr. Kevin Strange cautions there’s a long road to go to before the drug could be approved for humans, but it’s still a huge step forward, he says. For nearly two decades, researchers have focused on stem cell therapy to repair damaged hearts, and it’s not working.

“In our opinion, it’s a huge discovery,” said Strange, “Because it allows us to hopefully start driving a new and important direction of research in regenerative medicine.”

That could open the door to discovering other drugs that help humans regenerate damaged tissue.