Frog grows leg back after research which could be key to human limb regeneration

Scientists have regrown a frog's lost leg in a lab and say it brings dreams of human limb regeneration a step closer to reality.

Scientists successfully pulled off the feat with the animal and mammals could be next in line for experimentation.

A US team used a cocktail of drugs applied in a wearable dome which was sealed over the frog's stump.

After just 24 hours, the dome was removed and the leg's 18-month regrowth period had begun.

The groundbreaking therapy has excited the study's first author Dr Nirosha Murugan, who said: "It's exciting to see the drugs we selected were helping to create an almost complete limb.

The scientist at Tufts University added: "The fact it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action."

Researchers triggered the regenerative process in African clawed frogs by enclosing the wound in a silicone cap – called a BioDome.

It contained a silk protein gel loaded with five drugs – each fulfilling a different purpose. They dampened inflammation and inhibited production of collagen which causes scarring. They also encouraged new nerve fibres, blood vessels and muscle.

The bioreactor provided a local environment and signals that tipped the scales away from the natural tendency to close off the stump – and toward the regenerative process.

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Dramatic growth of tissue was observed in many of the treated frogs – re-creating an almost fully functional leg.

The new limbs had bone structure extended with features similar to a natural counterpart's.

They also had a richer complement of internal tissues, including neurons.

Several 'toes' grew from the end of the limb – although without the support of underlying bone.

The regrown limb moved and responded to stimuli such as a touch from a stiff fibre which meant the frogs were able to swim as normal.

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The researchers explored the mechanisms by which the brief intervention could lead to long-term growth.

The first stage of growth after loss of a limb is the formation of a mass of stem cells at the end of the stump called a blastema.

It's used to gradually reconstruct the lost body part. The wound is rapidly covered by skin cells within the first 24 hours after the injury – protecting the reconstructing tissue underneath.

The five-drug cocktail represents a significant milestone toward the restoration of fully functional frog limbs.

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Corresponding author Prof Michael Levin, director of the Allen Discovery Center at Tufts, said: "We'll be testing how this treatment could apply to mammals next.

"Covering the open wound with a liquid environment under the BioDome, with the right drug cocktail, could provide the necessary first signals to set the regenerative process in motion.

"It's a strategy focused on triggering dormant, inherent anatomical patterning programs, not micromanaging complex growth, since adult animals still have the information needed to make their body structures."

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