Whether it's the Mexican axolotl that can regrow its legs in weeks, the green anole lizard that sprouts new tails as needed, or the ability of newts to replace pretty whatever limb they happen to be missing, the regenerative abilities of certain creatures have much to teach the world of medical science. A new breakthrough out of Tufts University has now resulted in partial limb regeneration in adult frogs that usually lack such capabilities, raising hopes the research could ultimately benefit human amputees.

The scientists enlisted an animal called the African clawed frog for their work, as a way of investigating what they see as an under-explored area of biomedical research. Regenerating limbs in humans would be a massive breakthrough for obvious reasons, and for a long time scientists have probed natural mechanisms in animals like those mentioned above in search of techniques that could ultimately be adapted to our species.

The African clawed frog can actually regenerate limbs, but only in its youth during the tadpole and froglet stages, before losing the ability altogether as it becomes an adult. When an adult loses a limb, it will generally grow a spiky stump full of cartilage instead. The research is a way of exploring how new limbs can be generated in organisms that have lost, or never had, the capability.

At the heart of the technique is a new kind of wearable bioreactor developed in-house at the Tufts' School of Engineering. The device is designed to be attached to the wound and uses a silk protein-based hydrogel to deliver small molecule compounds to the injury site. Future plans will look at additional enhancing factors, but the team's experiments so far have involved the delivery of the steroid hormone progesterone.

"We looked at progesterone because it showed promise for promoting nerve repair and regeneration," says Celia Herrera-Rincon, lead author of the study. "It also modulates the immune response to promote healing, and triggers the re-growth of blood vessels and bone. Progesterone can also regulate the bioelectric state of cells, caused by cells passing ions across their outer membranes, which is known to drive regeneration and body pattern formation."

The team used the bioreactor to deliver progesterone over a 24-hour period, and found that it triggered nine months of changes in gene expression, innervation and patterned growth. This resulted in a paddle-like structure instead of the typical cartilaginous spike, as seen above. This partial regeneration of the hind limbs could provide the basis for further research into how bioreactor devices can trigger regenerative abilities in species usually incapable of limb regeneration.

"We'll be using the bioreactor model as a new platform for finding 'master regulator' control points, activated by drugs which, after a very brief treatment, trigger a long program of tissue growth and remodeling, as well as other factors that support the entire process of regeneration," says Michael Levin, corresponding author on the paper. "The fact that the model applies treatments locally, which can also be varied over time and location on the wound, makes this a powerful tool for discovering regeneration therapeutics."

Looking to build on this breakthrough, the researchers have already begun work exploring its potential in mammalian species, while their latest research is published in the journal Cell Reports.

View gallery - 2 images