Using a cocktail of up to five drugs – five pro-regenerative compounds – applied in a portable silicone device attached to their stumps, a team of scientists from Tufts University and Harvard University have managed to regenerate lost frog legs from a species that cannot naturally regenerate its own limbs . Each drug served its own purpose, including reducing inflammation, inhibiting collagen production that would lead to scarring, and encouraging new growth of nerve fibers, blood vessels, and muscles.
One more step in regenerative medicine
His goal, in the future, is to test his technique on mammals. And, while it’s still very early days for this stage of the research, they suggest this novel approach could be applied to humans with missing limbs , something that, for now, is relegated to the realm of science fiction.
Many creatures have the ability to fully regenerate at least some limbs, including salamanders, starfish, crabs, and lizards. Humans are capable of closing wounds by growing new tissue, and our livers have a remarkable ability to regenerate to full size after 50% loss. But the loss of a large, structurally complex limb (such as an arm or leg) cannot be restored by any natural process in humans or mammals in general.
During the experiment, after applying the BDNK, 1,4-DPCA, RD5, GH and RA cocktail for 24 hours and placing the amputated limbs of the frogs in a silicone cap with a silk protein gel together with these drugs, over the course of 18 months, African clawed frogs (Xenopus laevis ) had ‘nearly fully functional’ limbs restored , including fingers, which they used to help them swim.
“The fact that it only required a brief exposure to the drugs to kick-start a months-long regeneration process suggests that frogs and perhaps other animals may have latent regenerative abilities that can be activated, ” explains Nirosha Murugan, a research affiliate at the Allen Discovery Center at Tufts University and leader of the project that publishes the journal Science Advances.
Their new limbs featured a bone structure similar to natural limb bone, a richer complement of internal tissues, including neurons, and even some “toes” at the end of the limb.
The regenerated limb moved and responded to stimuli such as the touch of a stiff fiber, and the frogs were able to use it to swim in the water, moving as a normal frog would.
The team now wants to regenerate frog limbs that are even more functionally complete, with normal fingers, webs, and more detailed skeletal and muscular features, before moving on to mammals. Much work remains to be done.
Referencia: Nirosha J. Murugan, Hannah J. Vigran, Kelsie A. Miller, Annie Golding, Quang L. Pham, Megan M. Sperry, Cody Rasmussen-Ivey, Anna W. Kane, David L. Kaplan, Michael Levin. Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis. Science Advances, 2022; 8 (4) DOI: 10.1126/sciadv.abj2164