Adult frogs can’t usually regrow a lost leg, but they can after treatment with a regenerative cocktail – and the new leg even contains functioning nerves
26 January 2022
Adult frogs can gain the ability to regrow a lost leg if they are treated with a device containing a silk gel infused with five regenerative chemicals. The limbs the frogs grow can apparently move and sense as well as the original legs.
Although tadpoles and young froglets can regenerate hindlimbs, adult frogs, like humans, lack the capacity to regrow their legs.
“We were [looking for] a way to kickstart regeneration in an organism that normally can’t regenerate a limb,” says Nirosha Murugan at Algoma University in Ontario, Canada.
Murugan’s colleagues – including Michael Levin at Tufts University in Massachusetts – had previously designed a small cylindrical device, called the BioDome. This is made of a silicone outer sleeve surrounding an inner layer containing silk from silkworms that has been processed and incorporated into a polymer called a hydrogel. The researchers have now explored the device’s potential to help in limb regeneration.
First, they amputated the right hindleg of 115 frogs (Xenopus laevis). The frogs were then placed into one of three groups. Those in the first group wore a BioDome over the wound site that had been loaded with a cocktail of five drugs known to help cells regenerate. Frogs in the second group wore BioDomes without the drug cocktail and the third group received no treatment at all. The frogs that wore a BioDome did so for one day, after which it was removed.
“With the cocktail, we put the big signals in to restart the major regenerative pathways,” says Murugan.
The researchers tracked limb growth for 18 months. By the end, frogs that received a BioDome containing the drug cocktail regrew legs with digit-like structures at the end. Each frog could use its new leg to stand on, swim and push off walls.
Further investigation showed that the new legs carried nerves, blood vessels and bone in patterns similar to those seen in the original legs.
By using a tiny bristle to prod the tips of the limbs and watching how each frog responded, the team found that a similar force was needed to trigger a reaction in the regrown limbs as in original limbs. This confirmed that the nerves in the regrown limbs were functioning.
The frogs in the other two groups formed a slender, non-structured flap of tissue called a “spike” at the amputation site. The frogs that wore a BioDome that lacked the drug cocktail grew slightly longer spikes than the untreated frogs.
Frogs that received the BioDome without drugs showed a wide range of sensitivity to prodding of their spikes, while untreated frogs showed a complete lack of feeling in their spikes.
Levin says the work is exciting and represents the first time that this combination of drugs has been used to trigger limb regeneration.
“None of us can say what it feels like to be a frog [with a regrown limb], but from what we can measure, there were no differences compared to a non-injured limb,” says Levin. Although the toes were shorter than normal, the limbs were still growing at the end of the experiment and it is possible they could have eventually formed completely, says Levin.
“It is striking that the brief, 24 hours, treatment reported in this work has such a long-lasting effect,” says Lin Gufa at Tongji University in China.
It is simpler and more straightforward compared with methods currently used, such as cell transplantation or multiple rounds of electric stimulation, says Lin. Murugan, Levin and their colleagues also point out in their research paper that these current methods are mostly applied to animals – like axolotls – with a natural ability to regenerate limbs, and not to animals like adult frogs that lack this ability.
The researchers are now testing the approach in mammals. Murugan thinks it may have the potential to be tested in humans one day.
Journal reference: Science Advances, DOI: 10.1126/sciadv.abj2164
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