Lost frog legs regenerated – wissenschaft.de

Frogs are usually like us: lost limbs do not regrow. But now scientists have managed to induce a regeneration process in adult clawed frogs. They placed a portable bioreactor on the stump of the amputated legs, which healed the wound for 24 hours with an elixir of special active ingredients. This triggered an 18-month growth period during which the frogs eventually re-produced an almost complete leg with functional abilities. The results could aid in the development of regenerative medicine procedures, the researchers said.

Millions have come to terms with the loss and are dependent on prostheses: If a person loses a limb as a result of an illness or accident, it is known that the body cannot grow it back. Because the ability to regenerate is limited to the formation of scar tissue above the wound. This is also the case with animals. However, exceptions suggest that there is at least some basic potential for regeneration: some species are able to fully regenerate at least some limbs, including salamanders, starfish, crabs and lizards. The best known example is probably the axolotl (Ambystoma mexicanum). This amphibian has the amazing ability to restore limbs and organs.

Until now, scientists have focused mainly on studying these animal masters of regenerative abilities. On the other hand, a team led by Nirosha Murugan of Tufts University in Medford is investigating the extent to which it is possible to induce new limb growth in animals that are normally unable to do so. The models are adult clawed frogs (Xenopus laevis). Each of the test animals was amputated for the experiments with one hind leg. In order to be able to treat the resulting wound with test agents, the team developed a portable bioreactor made of silicone material with silk proteins. They call this little cap “BioDome”.

The functional leg grows back

As reported, a cocktail of five regenerative substances proved surprisingly effective in their research. The elixir was applied to the wound via the BioDome for 24 hours. As the scientists explain, each active ingredient served a specific purpose: inflammatory processes were inhibited, the production of scar-forming collagen was stopped, and the growth of nerve fibers, blood vessels and muscles was stimulated. The result became apparent within 18 months: scientists noticed strong tissue growth in many of the treated frogs, which eventually led to them re-producing an almost complete leg.

The regenerated limb was found to have a bone structure similar to that of the original leg. Toe-like structures also formed, but the elements at the ends of the frogs’ legs remained incomplete, the researchers admit. Basically, however, in some cases, a functional limb developed, including neural structures, the researchers reported: the legs moved, they responded to tactile stimuli, and frogs were able to use them while swimming. “It was exciting to see how the active ingredients we selected helped regenerate an almost complete limb,” says Murugan. Scientists concluded that the cocktail of five active ingredients represents a significant advance in the field of research.

Potential for Regenerative Medicine

“The fact that a brief exposure to the active ingredients was enough to begin the regeneration process lasting several months suggests that frogs and possibly other animals have dormant regenerative abilities that can be activated,” says Murugan. The team has now found preliminary indications of which processes were triggered by their treatment strategy: through molecular analysis, they determined that in the first few days after treatment, known systems that normally take place in the developing embryo were activated to produce the Structure body.

The results also offer hope for the long-term goal of improving people’s ability to regenerate. The BioDome system concept can also be of importance. “In mammals, lesions are usually exposed to air or contact with substances, so it can take days or weeks to close scar tissue,” says co-author David Kaplan of Tufts University. “On the other hand, the use of BioDome Cap can create conditions in the first 24 hours that, together with the appropriate drug, will allow the reconstruction process without interfering with the scar tissue.”

Scientists will now work to optimize combinations of drugs and growth factors to further improve regeneration performance in frogs. In addition, they are already planning a transition from amphibians to mammals: “We will test how this treatment can be applied to mammals,” says senior author Michael Levin of Tufts University. “Covering an open wound with a liquid environment underneath the BioDome could, with the right cocktail of drugs, provide the necessary first signals to start regeneration processes” – the scientist hopes.

Source: Tufts University, article in the journal: Science Advances, doi: 10.1126 / sciadv.abj2164

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