A frog partially submerged in water looking straight ahead
A frog partially submerged in water looking straight ahead

Drug Cocktail Triggers Regeneration of Amputated Frog Legs

A new chemical treatment allowed African clawed frogs, which normally don’t regenerate limbs, to regrow functional hind legs following amputation.

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Dan Robitzski

Dan is a Staff Writer and Editor at The Scientist. He typically works on the news desk and joined the team in 2021. He has a background in neuroscience and earned his master's in science journalism at New York University.

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Jan 26, 2022

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Among vertebrates, the ability to regenerate functional limbs or other body parts is rare. Salamanders can regrow entire limbs, deer grow new antlers, and zebrafish can regrow large portions of their hearts. Now, research published in Science Advances today (January 26) reveals a possible way to trigger functional limb regeneration for animals that normally can’t pull it off. In the study, African clawed frogs (Xenopus laevis) that had a hind leg amputated and then were treated with regenerative drugs grew new legs that functioned similarly to those of frogs that never lost a leg in the first place.

After amputating 115 female frogs’ right hind legs, the researchers divided the frogs into three groups, each of which received different treatments, according to the paper. In addition to a control group, one group of frogs had their stump encapsulated and sealed off in a small silicon cap that the researchers call a “BioDome.” A third group had their legs capped with a BioDome that had been loaded with a cocktail of five drugs. BioDomes were removed after just 24 hours, and researchers observed the legs over the next 18 months.

The two groups of frogs that didn’t receive a drug treatment failed to regenerate a new leg. Instead, they grew a long flap of tissue called a “spike,” according to New Scientist, which grew slightly longer and developed a greater sensitivity to touch among frogs that received a drug-free BioDome. The new legs of the frogs that received the drugs contained bones, vasculature, and functional nerves that resembled those of a normal leg, according to the paper. The legs also grew toe-like digits—which failed to develop bones—and the frogs could walk, push, and swim nearly as well with their regenerated legs as they could before amputation.

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“Using the BioDome cap in the first 24 hours helps mimic an amniotic-like environment which, along with the right drugs, allows the rebuilding process to proceed without the interference of scar tissue,” study coauthor and Tufts University biomedical engineer David Kaplan says in a university press release.

As is often the case with animal regeneration research, the scientists behind the study have their eyes set on someday regenerating lost, amputated, or missing limbs in humans. However, clinicians wouldn’t be able to put a medicated BioDome onto a human amputee and expect a limb to grow back. “An immediate translation of this strategy to humans is unlikely because a regenerative spike does not occur in humans as it does in Xenopus frogs,” Northeastern University biologist James Monaghan, who didn’t work on the study, tells CNN. Still, he adds that “this work is exciting because it shows that endogenous regenerative processes can be enhanced by a short application of a drug cocktail.”

“It’s exciting to see that the drugs we selected were helping to create an almost complete limb,” Algoma University researcher Nirosha Murugan, the first author of the paper who was affiliated with Tufts at the time, tells The Guardian. “The fact that it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests that frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action.”

Study coauthor and Tufts University biologist Michael Levin tells The Wall Street Journal that he suspects a similar treatment could help human amputees by spurring regrowth of blood vessels, skin, or nerves at the site of their amputations, which could allow for better fit and control over prosthetic limbs. He also adds that there’s “nothing leg-specific” about the drug cocktail, hinting that it could have more general utility.

“The study has extremely exciting ramifications for regenerative medicine,” Robert Lanza, a regenerative medicine researcher at Wake Forest University School of Medicine who didn’t work on the new study, tells the Guardian. “Although frogs have much greater regenerative capacity than humans, this is a very important first step. With the right combination of drugs and factors a similar approach could potentially spur regeneration and restore lost function in humans.”