Frogs can grow amputated limbs again with a new mixture of drugs

Such extraordinary forces are avoided by most animals, including humans, although scientists have long sought to understand and copy them in a quest to regenerate limbs for millions of patients who have been amputated, including diabetics and victims of trauma.

Now, U.S. researchers on Wednesday said they were able to trigger the regrowth of an amputated leg in a type of African cleft seed (Xenopus laevis), in what they described as a “step closer to the goal of regenerative medicine.”

The technique used by the team of scientists, based at Harvard University’s Wyss Institute and Tufts University, involved applying a mixture of five drugs to the tip frog’s tip-like stump, sealed with a small silicone dome. The cocktail was only applied for 24 hours, but after 18 months the limb was almost fully functional. That frogs living in water were able to swim and respond to touch. They also grew several toes, but not the bond between them.

The research was published in the journal Science Advances on Wednesday.

The results were “impressive” and “exciting,” said James Monaghan, an associate professor of biology at Northeastern University. He was not involved in the research.

“Xenopus frogs are somewhere between a salamander that grows a limb almost perfectly and a mammal that generates a scar after amputation. Adult Xenopus frogs regenerate a tip after amputation, but the tip lacks any pattern like a limb,” Monaghan explained.

“This study is significant because it shows that pattern formation, although not perfect, can be induced in a limb that typically regenerates only one tip,” Monaghan said via email.

Activation of cell growth and organization

The team said the fact that only a brief exposure to the drugs set in motion a month-long regeneration suggested that frogs – and perhaps other animals – have dormant regenerative abilities that can be triggered into action.

Shown is the dome that the team attached to a frozen stump that contained a cocktail of the drugs.

“An immediate translation of this strategy into humans is unlikely because a regenerative peak does not occur in humans as it does in Xenopus frogs. Yet this work is exciting because it shows that endogenous regenerative processes can be improved by a short application of a drug cocktail, “Monaghan said.

The strategy the team used relied on triggering dormant mechanisms in the frog’s body instead of trying to “microcontroller its growth,” said study author Mike Levin, Aquarius Bush Professor of Biology and Director of the Allen Discovery Center at Tufts.

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“I think the way to really achieve regenerative medicine is to harness the collective intelligence of the body’s cells. They already know how to build all these organs. They did it during fetal development. All that information is still there,” he said. Levin.

“For me, the goal is to identify triggers, very simple forms of stimuli that will kickstart the cells and convince them to build, whatever it is you want them to build.”

The drugs included molecules that are important for the development of limbs or that have anti-inflammatory properties. Levin said it was the first cocktail they tested and it was possible that another combination of drugs and growth factor could have better results.

“It has the circumference and the kind of features like a normal limb, some buds that turn into toes. It does not yet have the whole correct terminal structure. It does not have the long toes, woven – we had ‘we do not get that far, it we can have if we let it go further, “he said.

Regenerative medicine vs. prostheses

The research team used the technique on more than 100 frogs, but the results were “not perfect in all cases.” Levin said the frogs were not largely identical to laboratory mice, which could be a factor, or there were discrepancies in the operation performed to attach the dome. The next phase of research would test the technique on mammals such as mice.

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Levin and his colleagues have also used seed stem cells to create self-replicating living robots, which they call xenobots. The common thread between the two research streams is to understand the signals required for cells to organize themselves into complex tissues that form a structure, such as a limb or an entire organism.

Ashley Seifert, an associate professor of biology at the University of Kentucky who studies regeneration of animals but was not involved in the research, said that progress with prostheses provided more hope than regeneration of limbs for people with amputated limbs lost due to trauma or illness. as diabetes.

“Will we one day be able to regenerate a human digit or even a limb? Probably, but how long we have to wait is impossible to predict,” Seifert said.

“A step in that direction will be when regenerative biology fully embraces new regenerative models, especially certain species of mammals. This and comparative studies will help us understand how and why regeneration fails in some contexts and succeeds in others.”

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