Biology: Researchers use drug cocktail to regrow amputated frog legs

Science biology

Researchers are regrowing amputated frog legs with a cocktail of drugs

Claw frogs like this one have grown functional legs Claw frogs like this one have grown functional legs

Claw frogs like this one have grown functional legs

Source: Pouzin Olivier

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Clawed frogs cannot naturally regenerate lost limbs. But it can be induced by drugs. Within 18 months, the researchers were able to regrow fully functional legs.

inResearchers have regrown frogs’ previously amputated hind legs. To do this, they applied a cocktail of drugs to the wound, they report in the journal Science Advances. In the next year and a half, the animals grew functional legs. The researchers hope that their experiment will one day help develop similar therapies for people who have lost an arm or a leg, for example.

Scar tissue forms over a wound in humans and most animals after the loss of a limb. This tissue protects against blood loss and infection, but also prevents further growth. In some animals, the ability to regenerate tissue is much more pronounced: the axolotl, for example, can repair limbs, organs and even parts of the brain after loss. If you cut planarians, a genus of flatworms, in two, two new specimens emerge from the piece.

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Scientists from Tufts University in the US and the Wyss Institute at Harvard University used adult clawed frogs (Xenopus laevis) for their experiments. You can’t actually regenerate lost limbs. If they lose a leg, for example, only a thin thorn grows back. To test whether the regeneration process could be initiated, the researchers first removed the hind leg from 115 adult female specimens.

A third of the animals received no further treatment, and another third had a silicone cap called a “BioDome” placed over the stump containing a silk protein gel. The last third was also equipped with such a bioreactor, but the protein gel also contained five drugs: one reduced inflammation, the other inhibited the production of collagen, which would lead to scarring. The rest stimulated the growth of nerve fibers, blood vessels and muscles. “BioDome” remained on the stumps for 24 hours.

A cocktail of drugs makes a difference

In fact, the brief treatment triggered an 18-month growth phase in the two “BioDome” groups. The researchers observed significant tissue growth, with an almost fully functional leg regenerated, especially in frogs treated with the drug cocktail. The limbs had a bone structure similar to that of a natural hind leg. In addition, several “toes” grew, which, however, did not contain bones and also did not develop webs.

The new legs responded to touch stimuli, and the frogs could swim and move like normal animals. “The fact that only a brief exposure to the drugs was required to initiate a months-long recovery process suggests that frogs, and perhaps other animals, have dormant recovery abilities that can be activated,” comments first author and neuroscientist Nirosha Murugan in a statement. Analyzing the underlying mechanisms in more detail, the researchers found that the treatment activated molecular mechanisms known from embryonic development.

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For Maximina Yun, head of the research group at the Center for Regenerative Therapies Dresden (CRTD), the study represents progress for the entire field of research, however, given the missing networks and incompletely developed bones, one can only speak of partial regeneration. : “Considering the observed functionality of the legs and their sensitivity, it is already very good,” said the scientist, who was not involved in the study. According to Yun, the duration and regimen of treatment, as well as the exact dose and composition of the drug cocktail, must now be examined in more detail to promote optimal growth.

Unclear effect on mammals

When evaluating the experiment, it must be taken into account that although the regenerative capacity of adult clawed frogs is reduced, the animals are still able to some extent to replace lost limbs – even if, in the case of the leg, there is only a spur. growing again. Yun explains that other studies have already shed light on certain cellular processes that could lead to the loss of regenerative capacity in adult frogs. It would be important to investigate how the bioreactor affects these processes.

The authors of the study themselves are already considering experiments with other animal species, as co-author Michael Levin announces: “Next we will test how this treatment can be used in mammals.” It enables the regeneration of hands and feet in humans.

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Biologist Yun cautions that human limbs are very complex and also very large compared to the rest of the body: “We cannot yet say whether the procedure described in the study would result in regrowth of human limbs,” says Yun, who researches regeneration capabilities. salamanders themselves. Even independently, research into super-regenerators – that is, animals that can regrow complex structures – could, according to the scientist, lead to applications in humans: “Even if regrowing arms or legs proves to be an impossible task, can these the findings contribute to therapies that target other organs or structures. In that sense, this study has great potential.”

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