Tufts University researchers led by biologists and engineers have found that delivering progesterone to an amputation injury site can induce the regeneration of limbs in otherwise non-regenerative adult frogs—a discovery that furthers understanding of regeneration and could help advance treatment of amputation injuries.

The researchers created a wearable bioreactor attached to the wound site that delivered the progesterone locally for a 24-hour period. Results showed that it had a lasting beneficial effect on tissue regrowth, allowing the frogs to partially regenerate their hind-limbs. A day of exposure led to nine months of changes in gene expression, innervation, and patterned growth, the researchers found. The finding, published November 6 in Cell Reports, suggests the drug-device combination could be a new model for systematically testing and deploying therapeutic cocktails that could induce regeneration in non-regenerative species.

Xenopus laevis, or the African clawed frog examined in this study, can regenerate limbs when in their tadpole and froglet stages, but gradually lose that capability as they develop into adults. Until now, it was unknown whether adult frogs were capable of significant regeneration response. The study authors noted that while restoration of limbs has been an endpoint sought in biomedical research, little has been reported of rebuilding or repairing lost limbs in non-regenerative animals. As a result of this study, the researchers are exploring factors and modes of treatment to better understand how to induce regeneration in organisms that have lost, or never had that capability.

“We looked at progesterone because it showed promise for promoting nerve repair and regeneration. It also modulates the immune response to promote healing and triggers the regrowth of blood vessels and bone,” said Celia Herrera-Rincon, PhD, lead author of the study. “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.”

This story was adapted from materials provided by Tufts University.

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