A team at Tufts University and Harvard University has brought scientists a step closer to the goal of regeneration medicine by using a drug cocktail to regrow a frog’s amputated legs. 

Only a few animals in the world are able to regrow some limbs: salamanders, lizards and crabs. They do it through blastema cells, when a mass formation of stem cells occurs at the end of a stump almost immediately after the limb is lost, so the regrowth process can begin.

Frogs are like humans and mammals, however, in that they cannot regenerate complex limbs like arms or legs. Instead, our bodies, along with those of frogs, use scar tissue to protect wounds from blood loss and infection.

In a peer-reviewed study published in the journal Science Advances on Wednesday, scientists from the two universities wanted to see whether limbs could be regenerated on African clawed frogs with amputated legs. 

Tufts scientists created a five-drug-cocktail silicone cap. In the cap were drugs meant to reduce inflammation, a protein substance to help with scarring, and drugs meant to help the growth of blood vessels, muscles and nerve fibers. The team put the cap on the frogs for 24 hours. 

“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,” David Kaplan, professor engineering at Tufts and co-author of the study, said in a news release. 

The cap was taken off after the 24 hours, and the team spent the next 18 months observing any changes. At the end of the period, many of the tested frogs had not only regrown the legs, but the limbs also had become nearly fully functional.

The legs had a new bonelike structure, internal tissues and new “toes” without bones. They responded to touch, and the frogs were able to use them to swim and go back to a normal way of life. Nirosha Murugan, researcher at the Allen Discovery Center at Tufts and lead author of the study, said it was “exciting” to see the drugs helped create “an almost complete limb.”

The team said their research with the silicone cap and the drug cocktail is far from done. They add that it may be possible to strengthen or add to the drug cocktail to help regenerate fully complete limbs with actual toes and bones. Michael Levin, director of the Allen Discovery Center at Tufts and a study co-author, said the next step is to test the procedure out on mammals, which eventually could lead to human regeneration.

“The fact that it required only a brief exposure to the drugs to set in motion a monthslong regeneration process suggests that frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action,” Murugan said.

Source: USA Today

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