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  • Jaejeong & Jaeah Kim

Salamanders: Animal Kingdom's Reigning King of Regeneration

(Eastern Tiger Salamander)

Thousands of soldiers face countless casualties in battlefields every year, losing limbs, getting serious burns, losing organ function, and facing other debilitating injuries. In order to find better treatment options for these veterans, the pentagon recently funded a $250 million project for research on regenerating human skin, muscles, ears, and other organs for injured veterans. Some of that funding is also being dedicated into establishing the Armed Forces Institute of Regenerative Medicine, that will focus on human limb regeneration research.

Limb regeneration doesn’t mean growing arms and legs in a test tube, but rather means that a person would regenerate a limb naturally on the spot that it was amputated/removed. Much research indicates that humans have the genetic potential for limb regeneration, but that these genes are dormant in an adult human body. Luckily, scientists won’t have to start from scratch when researching how to reignite human genetic potential for limb regeneration, as we have the salamanders –highest order of animals capable of regenerating body parts– to look towards!

So how do salamanders achieve such anatomical wonder? The process of limb regeneration in a salamander is very complex, but in a nutshell, it involves shuffling the cells around at the wound site, and assigning them new functions & specializations.

When a salamander loses a limb or a tail in a fight, the salamander’s epidermal cells in the region of limb loss migrate to cover up the open flesh, and this layer of cells gradually thicken in the course of a few days, creating the apical epithelial cap. Under this apical epithelial cap, undifferentiated cells called fibroblasts congregate. (undifferentiated means that a cell has not yet developed into a particular cell variant, and is thus free to become a multiple variety of cells) After this first phase, a blastema (mass of stem cells) develop from the congregation of fibroblasts, and this blastema is what eventually forms the new body part.

Research has shown that the expression of a protein called nAG is what kickstarts the initial blastema development in salamanders, and that the genetic coding in the blastema (more specifically the HOX genes of fibroblast cells) contains positional information about the location of the missing body part. This positional information is how the blastema knows how/where to regenerate, and what allows the blastema to regenerate in a non-defective way.

Researchers hope that they can apply this regenerative mechanism of salamanders on humans one day, generating blastemas from stem cells, and ultimately regenerating whole humans limbs and organs. However, until then, I guess salamanders are the king of regeneration in the animal kingdom.


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