US researchers have figured out how to use a cocktail of substances to regrow an amphibian’s amputated hind legs.
The animal, the African frog Xenopus laevis, is not able to naturally recreate its limbs as an adult, which opens up the possibility that similar strategies could help human beings who suffer amputations in the future.
Of course, this kind of medical application is still a distant dream. Even so, the work coordinated by Michael Levin, from the Biology Department at Tufts University, shows that scientists are mastering with increasing precision the details of the process of reconstructing injured parts of the body from their biochemical bases.
Even if this doesn’t go as far as returning entire arms or legs to injured people, knowledge about this process is likely to have important therapeutic impacts in several areas.
Levin and his colleagues describe in detail the experiments with females of X. laevis in an article in the specialized journal Science Advances.
The species is already the subject of decades of laboratory study — one of the first pregnancy tests for humans, for example, was developed with the help of animals. Therefore, many details of their biology are well known, starting with the fact that they lose the ability to regenerate as adults, although they manage to perform this type of feat when they are still tadpoles.
Studies with other animals and with the cultivation of cells and tissues had already pointed out some molecules that seem to work as key signals of regeneration in the body.
At the same time, it was necessary to dose the use of these substances so that the process took place in a controlled way, without the multiplication of cells at the injured site becoming exaggerated — something that could even generate tumors, for example.
To get around this, the researchers used a small device they dubbed the BioDome — basically a small cup containing a gel containing molecules derived from silk. The apparatus serves as a system for the gradual release of the regeneration cocktail, added to the gel.
In amphibians that had half of one of their hind legs surgically amputated, the limb stump was inserted into the BioDome and left there for 24 hours.
The gel had five components: growth hormone, a factor that favors the multiplication of nerve cells, a molecule that reduces inflammatory processes, another that prevents the wound from turning into a simple scar and, finally, a chemically similar compound to vitamin A and important for the formation of the members during the embryonic process.
After the BioDome gel bath, the females of X. laevis returned to the tanks where they were being created until then and were monitored for over a year.
In addition to the group that received the full treatment, the scientists also followed animals that received only the BioDome, without the cocktail of regenerative substances, and another group that only underwent amputation. All interventions were performed with complete anesthesia of the animals.
In the latter case, there was only the formation of a scar on the animals. Only the use of the BioDome seems to have had some positive effect, leading to a slight regeneration of the paw. But the first group, whose paw stump was soaked in the cocktail for 24 hours, went through a continuous, long-term regeneration process, with effects that continued to appear even 18 months after the amputation.
The paw returned to a dimension very close to its original form, including the formation of extensions that resembled fingers (although without the original functionality).
The frogs were able to move normally in the water using their reborn limbs. Analysis of gene activation at the regenerated site showed that the same stretches of DNA important for embryonic development were working in the adult animals.
“Adult animals still have the information [genética] needed to create the structures of their bodies,” Levin explained in a statement released by Tufts University. The 24-hour stimulus would have been enough to “wake up” this innate developmental program. “Our next step is to test how this treatment could be applied to mammals.”
