A new study published in Science Advances shows that frogs with amputated legs were able to regenerate their functional limbs using a wearable bioreactor containing a cocktail of five drugs. The research is still in its very early stages, but it is suggested that this new approach could potentially be applied to people who have lost limbs in the coming years and decades.
The stars of the study were African clawed frogs, a species that cannot naturally regenerate its own limbs. Tufts University and Harvard University researchers placed a recently amputated limb in a silicone cup containing five pro-regenerative compounds, triggering the frogs’ dormant regeneration process. Each drug served its own purpose, including reducing inflammation, inhibiting the production of collagen that would lead to scarring, and stimulating new growth of nerve fibers, blood vessels, and muscles.
The frogs attached the drug-delivery bioreactor around their amputee hind legs for just 24 hours, and the progression of their limb formation was closely monitored over the next 18 months. Frogs that received the treatment experienced long-term increases in bone length, soft tissue pattern, and neuromuscular repair. His new limbs had a bone structure similar to that of a natural limb, a richer complement of internal tissue, including neurons, and even some “toes” at the tip of the limb.
Study author and Tufts University Professor biologist Mike Levin said: “These frogs live completely underwater, so they swim more than they jump, but their behavior was very similar to that of regular frogs – the new legs had a feel, could sense objects, and were able to move very well underwater. they were used.”
The team’s previous work had demonstrated with the BioDome how limb regrowth in frogs can be significantly promoted using a single drug, progesterone. However, these limbs grew like a simple spike and were not as functional as limbs augmented using five drugs in the new study.
Other scientists have taken a step in limb regeneration using an approach that has involved stem cells or gene editing in the past. But this new research takes an entirely new approach, using drugs and a bioreactor. Researchers believe this approach offers many benefits as it triggers natural anatomical modeling programs in animals that are dormant.
Professor Levin explains, “This study demonstrates that it is possible to elicit a regenerative response in animals that do not normally do so, without the use of genomic editing or stem cell implants.” “It’s also via a wearable bioreactor. Like some other approaches, no stem cell implants or foreign genes come in.”
Only a handful of animals with spinal cords can regenerate their limbs, especially salamanders and lizards. While there are no known mammals that can completely regrow lost limbs, some are thought to have unused regenerative powers. For example, people can enlarge their livers incredibly.
The researchers now plan to test whether their new technique works in mammals, in hopes to see if a finely tuned cocktail of drugs can trigger limb regeneration in humans.
Levin concludes, “Unlike some of the other approaches, the goal here is not to micromanage the process with stem cell 3D printing or the like, but to push the cells towards a limb-making program – the idea is to find a trigger, not implement all the applications. Our approach uniquely involves 24-hour treatment followed by more than a year of growth – the goal is to leverage cells’ ability to build complex structures. There’s a lot of work to be done to see how it will be applied in humans, but the future of regenerative medicine is very exciting.”
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