Can tadpoles help us understand human heart attacks?

April 25, 2019

undefined An image of a tadpole heart that highlights certain cells and heart muscle proteins in glowing fluorescence. These young animals are much better at heart repair than humans, a new study found. Image courtesy of Kyle Jewhurst, Tufts University.

Nearly 50 years ago, Al Green famously asked (in song form), How can you mend a broken heart?

It turns out tadpoles know the answer.

A recent study from the Allen Discovery Center at Tufts University shows that these young frogs can repair their own hearts from damage very similar to those that occur in human heart disease, and pinpoints some of the key biological players involved. If we could better understand the molecular pathways involved in that damage repair, we might be able to figure out how to trigger it in humans, improving treatments for the disease that is still the world’s leading cause of death.

Kelly McLaughlin, Ph.D., associate professor of biology at Tufts University and a member of the Allen Discovery Center, has long been interested in how organs like the heart develop naturally. More recently, she and her laboratory team began to study how — and whether — these organs repair themselves after injury. Past reports have shown that some animals, like salamanders and certain fish, can fully regrow large chunks of their hearts if sections are surgically removed.

“It struck me that for humans who experience cardiac damage, it’s not that someone takes out a giant piece of their heart and they have to make a new one,” said McLaughlin, who is the senior author on the tadpole study, which was published this month in the journal Development, Growth & Differentiation. “There’s a lower level of stress that damages the heart over time.”

She and Tufts graduate student Kyle Jewhurst set out to find an animal in between those that can fully regenerate body parts — like the salamander — and mammals, which are, scientifically speaking, regeneratively limited. Once we lose a body part, it’s gone for good. Researchers like McLaughlin at the Allen Discovery Center want to better understand the biology of regeneration in the hopes of one day being able to apply some of that healing power to humans.

They decided to look at the tadpoles of the African clawed frog, a species commonly used in developmental studies. These animals’ young can’t repair a heart with a large section removed, but McLaughlin and Jewhurst found that when they exposed the tadpoles to more subtle heart stressors, the animals were able to bounce back.

The researchers used a laboratory technique to induce a type of molecular stress known as oxidative damage, the same general class of stress that occurs in humans with cardiac disease. Tracking how the tadpoles healed in the following days, they saw that some of the molecular and cellular tools they used in that repair were the same as those other animals use to regenerate missing body parts — but some of the tools differed. It was a mix of salamander-like regeneration and more mammal-like wound repair.

“It uses some of the same things mammals have, we just don’t turn them back on when we’re supposed to,” McLaughlin said.

Improving how we treat human heart disease won’t be as easy as just flipping some cellular switch. Jewhurst and McLaughlin’s study is an initial step toward better understanding heart repair in animals that are good at heart repair. It will be a long road from there to making us better at mending our own hearts.

Their immediate next steps will be to dial up or down some of the molecular players they found to see if those tweaks make heart repair more or less efficient — and to see if they can then induce heart repair in adult frogs, which typically have lost such healing abilities. 

“It’s not something that can be directly applied to human medicine next week, but as I see it, every one of these studies gives you another piece of this very big puzzle,” McLaughlin said.

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