Recent Research on Mechanisms of Limb Regeneration

A number of research groups are engaging in mapping the biochemistry of limb and organ regeneration in species capable of such regrowth, such as salamanders and zebrafish. The hope is that the underlying systems of regeneration are merely inactive in mammals, not missing entirely, and therefore somewhere in all of this lies the basis for a therapy to provoke regrowth of missing tissues in adult humans. Whether or not this is the case is yet to be determined, though some of the evidence is promising: scarless healing of minor wounds present in MRL mice; the same outcome induced via inhibition of Cxcr4; the ability to selectively block zebrafish regeneration with the human ARF gene; and others. There are also the evolutionary arguments, such as those put forward by the researchers here. The more that researchers find very similar mechanisms of regeneration in widely diverse species, the more likely it is that those mechanisms also exist to be accessed in mammals.

Many lower organisms retain the miraculous ability to regenerate form and function of almost any tissue after injury. Humans share many of our genes with these organisms, but our capacity for regeneration is limited. Until the advent of sophisticated tools for genetic and computational analysis, scientists had no way of studying the genetic machinery that enables regeneration. Using such tools, scientists have identified common genetic regulators governing regeneration in three regenerative species: the zebrafish, a common aquarium fish originally from India; the axolotl, a salamander native to the lakes of Mexico; and the bichir, a ray-finned fish from Africa. The discovery of genetic mechanisms common to all three of these species, which diverged on the evolutionary tree about 420 million years ago, suggests that these mechanisms aren't specific to individual species, but have been conserved by nature through evolution.

The discovery of the common genetic regulators is expected to serve as a platform to inform new hypotheses about the genetic mechanisms underlying limb regeneration. The discovery also represents a major advance in understanding why many tissues in humans, including limb tissue, regenerate poorly - and in being able to possibly manipulate those mechanisms with drug therapies. "Limb regeneration in humans may sound like science fiction, but it's within the realm of possibility. 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."

In particular, the scientists studied the formation of a mass of cells called a blastema that serves as a reservoir for regenerating tissues. The formation of a blastema is the critical first step in the regeneration process. Using sophisticated genetic sequencing technology, researchers identified a common set of genes that are controlled by a shared network of genetic regulators known as microRNAs. The study also has implications for wound healing, which, because it also requires the replacement of lost or damaged tissues, involves similar genetic mechanisms. With a greater understanding of these mechanisms, treatments could potentially be developed to speed wound healing, thus reducing pain, decreasing risk of infection and getting patients back on their feet more quickly.

Link: https://mdibl.org/press-release/from-sci-fi-to-reality-unlocking-the-secret-to-growing-new-limbs/

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