Frogs Regrow Missing Limbs in a Lab Study

"Salamanders do it. So do starfish. And now scientists have shown that frogs can regenerate amputated limbs, once their stumps have been treated with a multidrug "cocktail." The findings, published Wednesday in the journal Science Advances, represent a notable advance in the field of regenerative medicine, which aims to replace human tissues and organs to restore normal function.

"This is really kind of a first step into figuring out what type of treatment methods might we use in the future," said Catherine McCusker, a University of Massachusetts Boston biologist who wasn't involved in the research. "I don't know if we'll be able to regenerate complete human limbs within my lifetime," she added, "but I think that we'll definitely be much closer, that's for sure."

In previous research, scientists tried to prompt limb regrowth in various animals using techniques including electrical stimulation and cell transplants. For the new study, a team led by Tufts University biologist Michael Levin took a different approach.

They amputated the hind legs of more than 100 anesthetized African clawed frogs and treated the stumps of some frogs with five growth-promoting drugs.

Silicone caps containing a drug-infused gel -- including compounds known to encourage the growth of nerve, blood vessel and muscle tissue and to block the formation of the collagen involved in scarring -- were sewn onto the stumps. The caps, which the scientists call BioDomes, were left in place for 24 hours before being removed.

Within two weeks, the researchers saw a significant increase in soft tissue growth among frogs that had been treated with the drug cocktail. Over the next 18 months, those frogs also showed increased bone regeneration and nerve and muscle development compared with their untreated counterparts. Ultimately, the treated frogs grew appendages with new knee joints and several boneless toes -- not fully formed legs but good enough for the frogs to swim with.

"There is nothing leg-specific about the drug cocktail," said Dr. Levin, who directs the Allen Discovery Center at Tufts. "In other words, we did not try to tell the cells what to do, how to make a leg, what does a leg look like."

He said he and his colleagues believe that "exploiting the native intelligence" of cells to trigger natural regrowth may point a way forward for the development of similar techniques for use in human amputees.

One challenge with human limb regeneration is that our bodies tend to produce a mass of scar tissue at the wound site. The tissue helps stop blood loss and prevent infection but may also prevent the regrowth of limb tissue. The new research suggests that capping the stump with a BioDome immediately following amputation might help interrupt that process." [1]

1. U.S. News: Frogs Regrow Missing Limbs in a Lab Study
Woodward, Aylin. Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 27 Jan 2022: A.3.