Unlocking the genetic code to limb regeneration and wound healing

Written by Alexandra Thompson

Scientists at the MDI Biological Laboratory (Bar Harbor, ME, USA) have identified a common genetic regulator governing regeneration across species, which they hope could help improve wound healing, prosthetic devices and full limb regeneration.

Epimorphic regeneration occurs in certain animals such as amphibians and teleosts, allowing them to fully regenerate body parts such as their limbs, tails and retina. Despite humans sharing many of these genes within these organisms, our adult regenerative capacity is limited. Therefore, scientists at the MDI Biological Laboratory in Bar Harbor (ME, USA) have carried out investigations into the genetics of these organisms to find out if these regenerative mechanisms could be triggered in humans.

Using next-generation sequencing, scientists at the MDI Biological Laboratory, an independent, non-profit biomedical research institution focused on increasing healthy lifespan and increasing our natural ability to repair and regenerate tissues damaged by injury or disease, have identified genetic regulators governing regeneration that are common across species.

Knowing that blastema formation is a key part of limb regeneration in animals with this capability as adults, researchers Benjamin L King and Voot P Yin looked at three regenerative species — the zebrafish, axolotl and the bichir — with the aim of finding out what genes control this event. They identified genetic mechanism controlling this process in all three — a common set of miRNA-regulated genes that diverged on the evolutionary tree aproximately 420 million years ago.

Specifically, they identified five commonly upregulated and five commonly downregulated miRNAs, as well as four novel tRNAs fragments with sequences conserved with humans.

This result implies that the same mechanism has been conserved by nature through evolution rather than being specific to certain organisms. “We didn’t expect the patterns of genetic expression to be vastly different in the three species, but it was amazing to see that they were consistently the same,” King explained.

The discovery of the common genetic regulators would explain why many human tissues have poor regeneration and could assist in the identification of methods such as drug therapies to activate improved human regeneration following amputation cause by traumatic injuries or as a result of vascular diseases such as diabetes and peripheral artery disease.

Yin explained: “The fact that we’ve identified a genetic signature for limb regeneration in three different species with three different types of appendages suggests that nature has created a common genetic instruction manual governing regeneration that may be shared by all forms of animal life, including humans.”

Even if total limb regeneration in humans was not possible, the ability to regenerate some of the nerves at the amputation point alone would have huge value for amputees, as it would allow the use of prostheses that interface with the nerves, allowing improved control.

It could also provide better understanding of wound healing, which involves similar genetic mechanisms. Any treatments accelerating this process would be of great value, as they would reduce pain and infection, and help patients back on their feet faster.

Sources: King BL, Yin VP. A conserved microRNA regulatory circuit is differentially controlled during limb/appendage regeneration. PLoS ONE doi:10.1371/journal.pone.0157106 (2016); https://mdibl.org/press-release/from-sci-fi-to-reality-unlocking-the-secret-to-growing-new-limbs/

Poster image via MDI Biological Laboratory in Bar Harbor (ME, USA).