Scientists have discovered that a strange creature known for its mysterious smile, the Mexican salamander, or "water sprite," may hold the key to regenerating amputated human limbs.
This critically endangered amphibian lives in the lakes and wetlands south of Mexico City. Scientifically known as Xolotl, after the Aztec god of fire, lightning, and twins, it is also nicknamed the "Peter Pan of the salamander" because it remains in tadpole form throughout its life and never grows larger. However, the real reason scientists are interested in it is its astonishing ability to regenerate entire limbs and even parts of major organs.
In a recent study, researchers combined three different organisms, each with a unique regenerative ability: the Mexican salamander, the zebrafish, and mice. Zebrafish can regenerate their fins and internal tissues repeatedly, while mice can regenerate their fingertips to a limited extent—an ability also present in humans when the nail bed remains intact. (If the fingertip, the part containing the nail, is amputated, but the nail bed, particularly the area known as the nail matrix, remains intact, the finger can regenerate remarkably, especially in children and sometimes in adults. Scientists believe that certain cells in the nail bed send signals to the surrounding tissues to initiate the regeneration process, so that the flesh, skin, bone, and nail itself grow in a coordinated manner to rebuild the amputated fingertip.)
The study, published in the Proceedings of the National Academy of Sciences, revealed a shared genetic mechanism among these three organisms, which may one day support the development of treatments for regenerating human limbs.
Josh Carey, an assistant professor of biology at Wake Forest University, said that this research showed that there are universal genetic programs driving the regeneration process in very different types of organisms, such as salamanders, zebrafish, and mice.
It is estimated that more than one million limb amputations are performed annually worldwide due to diabetes, accidents, cancer, and infections, according to the Global Burden of Disease project. This number is expected to rise as the population ages and diabetes rates increase. This has prompted researchers to seek treatments that regenerate natural limbs rather than relying on prosthetics.
The researchers focused on genes called SP genes and found them essential for the regeneration process in all three species. They discovered that skin regeneration in these creatures activates two genes, SP6 and SP8. When they used gene-editing techniques to remove the SP8 gene from the Mexican salamander, it prevented proper bone growth in its limbs, and similar effects were observed in mice that lacked both genes.
Based on these findings, the researchers developed an experimental gene therapy inspired by zebrafish, using a molecule called FGF8 that helped stimulate bone growth in mice and partially compensate for missing genes.
Although humans do not possess this regenerative ability by nature, the findings suggest that aspects of this process can be mimicked. Professor Carey said, "We can use this as a kind of proof of principle, that we may be able to offer treatments that mimic this regenerative pattern of skin in regrowing tissue in humans."
But the researchers emphasize that much work remains before these methods can be applied to humans, describing the study as an important step toward future treatments. Carey added that scientists are pursuing numerous solutions for limb replacement, including bioengineered scaffolds and stem cell therapies, and that the gene therapy approach in this study represents a new avenue that could complement these efforts.
