The recipe for the regrowth of a lost limb in a frog

In mammals, including humans, limb loss is irreversible. Whether it is due to injury or other causes such as diabetes, it can only be compensated for with possible prostheses. Rare exceptions are the regeneration of a limb in the very early stages of embryogenesis and at the fingertips in adulthood. However, some animals, such as the zebrafish or the salamander, have an exceptional ability to regenerate, which allows them to regrow a lost limb even into adulthood. In a recent study, Niroshe Murugan of Tufts University in the US and her colleagues were able to initiate such a regeneration process in smooth xenopus.Xenopus laevis). Like mammals, this southern African frog is usually not capable of such a feat in adulthood, after the metamorphosis stage.

When our body is subjected to this kind of injury, it reacts by covering the wound with a mass of scar tissue that prevents blood loss and protects the wound from infection. But these tissues also prevent any possible regeneration. Therefore, biologists sought to bypass this natural process in Xenopus, which lost its hind leg, in order to activate the regrowth mechanism. To do this, they wrapped animal wounds for twenty-four hours in a silicone cap containing silk protein gel, which itself was filled with a cocktail of five molecules, including, among other things, growth hormones. All together forms a bioreactor, a microenvironment in which biological reactions take place, which the researchers called “BioDome”. Each substance then plays a precise and complementary role in the repair of all tissues in the paw: reducing inflammation, inhibiting the production of collagen, a protein that promotes scar tissue, and stimulating growth. new nerve branches, blood vessels and muscles.

In many of the treated Xenopus, Nirosha Murugan and colleagues found a remarkable growth of new tissue spread over a period of eighteen months that restored an almost fully functional leg. It had a bone structure similar to that of a normal limb, and even a few “fingers”, albeit devoid of bone. The limb moved and responded to external stimuli, and the frogs could use it for swimming, moving through the water almost as well as their intact counterparts.

The researchers are enthusiastic because a very short twenty-four hour exposure to the drug cocktail was enough to start a full regeneration process that took eighteen months and restored a functional limb. Moreover, they determined that the mechanisms involved are controlled by well-known molecular signaling pathways, but are usually mobilized during embryonic development to shape the body. This suggests that these xenopes, and possibly other animals, are able to reactivate embryonic processes to kick-start regenerative processes into adulthood.

By continuing to experiment with different combinations of substances and growth factors, biologists hope to successfully grow fully formed and functioning limbs. In particular, they aim to test this experiment in mammals, which is the last step before considering possible therapeutic applications in humans. Eventually, regenerating a lost limb may no longer be the preserve of animal superheroes like the zebrafish or salamander.

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