Frogs with lost legs have been able to regenerate functional limbs using a wearable bioreactor that contains a cocktail of five drugs, as shown in a new study published in Science Advances. It’s still very early days for the research, but it's suggested this novel approach could potentially be applied to humans with lost limbs in the years and decades to come.
The stars of the study were African clawed frogs, a species that can not naturally regenerate their own limbs. Researchers from Tufts University and Harvard University triggered the frogs' dormant regenerative process by enclosing a recently amputated stub in a silicone cap containing five pro-regenerative compounds. Each drug fulfilled its own purpose, including reducing inflammation, inhibiting the production of collagen that would lead to scarring, and encouraging the new growth of nerve fibers, blood vessels, and muscle.
The frogs wore the drug-dispersing bioreactor around their amputated hind leg for just 24 hours and the progress of their limb generation was closely monitored for the next 18 months. The frogs that received the treatment experienced long-term increases in bone length, soft tissue patterning, and neuromuscular repair. Their new limbs featured bone structure similar to a natural limb’s bone, a richer complement of internal tissues, including neurons, and even some “toes” on the end of the limb.
“These frogs live entirely underwater, so they swim more than they jump, but their behavior was much more like that of normal frogs – the new legs had feeling, could sense objects, and were used for moving around very well underwater,” Professor Mike Levin, corresponding study author and pioneering biologist at Tufts University, told IFLScience.
The team's previous work showed how significant limb regrowth could be fostered in frogs using a single drug, progesterone, with the BioDome. However, these limbs grew as a simple spike and were not nearly as functional as the limbs grown in the new study using five drugs.
Other scientists have taken a stab at limb regeneration in the past using an approach involving stem cells or gene editing. This new research, however, takes a totally novel approach by using drugs and a bioreactor. The researchers believe this approach offers many benefits as it sparks the inherent anatomical patterning programs that are dormant in the animal.
“This work is showing that it's possible to induce a regenerative response in animals that normally don't do it, without using genomic editing or stem cell implants,” explains Professor Levin. “Our strategy uses a new cocktail of drugs that was never used before, and also delivers it via a wearable bioreactor. There are no stem cell implants or foreign genes introduced, as in some other approaches,” he continued.
Only a handful of animals with a spinal cord are capable of limb regeneration, most notably salamanders and lizards. While there are no known mammals that can fully regrow lost limbs, some hint that they harbor untapped regenerative powers. Humans, for instance, can grow back their liver to an incredible extent. The researchers plan to next test out whether their novel technique works on mammals, with the hope to eventually see whether a finely tuned cocktail of drugs could even trigger limb regeneration in humans.
“Unlike some of the other approaches, the goal here is to push cells toward the program of making a limb, not micromanage the process with stem cell 3D printing or anything like that – the idea is to find a trigger, not to implement all the details. This is why our approach uniquely has 24 hours of treatment followed by well over a year of growth – the goal is to capitalize on the ability of the cells to build complex structures,” Levin added.
“A lot of work remains to be done, to see how it's going to be applied in humans, but the future of regenerative medicine is very exciting,” he finished.