Out of all the various superpowers found in comic books and video games, regeneration is among the most astonishing. The idea of being able to regrow an arm or a leg whenever one is lost in an accident exemplifies a sort of uncanny magical ability straight out of science fiction. However, ability serves as an adaptive trait for several different animals around the world.
While notable examples include sea stars and certain species of lizards, the most prominent kinds of animals known for their regenerative capabilities are salamanders, a species known for its ability to regrow entire limbs and regenerate parts of major organs like their heart, their eyes and their spinal cord (ScienceAlert, “Limb regeneration in humans: salamanders may hold the key,” 06.22.2014). They possess such impressive regeneration abilities that immunologist James Godwin of the Australian Regenerative Medicine Institute at Monash University in Melbourne calls them “a template of what perfect regeneration looks like” (LiveScience, “Missing Parts? Salamander Regeneration Secret Revealed,” 05.20.2013).
One specific salamander species that deserves special attention is the axolotl, also known as a Mexican salamander (Ambystoma mexicanum). This amphibian in particular has a one-of-a-kind capacity for regeneration and is known for being able to regrow multiple structures like limbs, jaws, skin and even parts of its brain without evidence of scarring throughout their lives (Scientific American, “Regeneration: The axolotl story,” 04.13.2011). The sheer amount of damage that an axolotl can recover from is absolutely extraordinary. “You can cut the spinal cord, crush it, remove a segment, and it will regenerate. You can cut the limbs at any level–the wrist, the elbow, the upper arm–and it will regenerate, and it’s perfect. There is nothing missing, There’s no scarring on the skin at the site of amputation, every tissue is replaced. They can regenerate the same limb 50, 60, 100 times. And every time: perfect,” remarked Professor Stephane Roy at the University of Montreal. As a result, the axolotl is widely used as a model organism for studying regeneration. But this begs the question: can this amazing regeneration ability be somehow transferred to humans? If human beings had the same regenerative capacity as axolotls, the benefits would far surpass that of regrowing an arm or a leg or a finger. People would be able to repair or regrow their internal organs whenever an organ failure occurs without having to rely on intensive surgery. For instance, victims of car accidents may end up with major injuries to their backbone, their ribcage and all the soft major organs within, but a regeneration ability equivalent to that of an axolotl may have them walking normally after a mere few months. Not only that, the axolotl is over 1,000 times more resistant to cancer than mammals (Scientific American). Finding the source of this salamander’s regeneration capabilities could lead to unimaginable developments in modern medicine.
However, while the idea sounds fantastic, the execution is much more difficult than it looks. Compared to amphibians, humans have very limited regenerative capabilities, restricted primarily to their skin. So far, research into salamanders have led scientists to pinpoint the blastema, a mass of immature cells typically found in the early stages of an organism’s development, as the key to regeneration (Futurism, “Human Limb Regeneration: How Close Are We To The Finish Line?,” 08.29.2016). Essentially, when an adult salamander limb is amputated, the outermost layer of skin covers up the wound and sends signals to nearby cells, which prompts the mature cells to form the blastema. From there, the immature cells start to divide and differentiate into specific muscle and nerve cells until a different signal or some form of memory tells the cells to stop regenerating (NCBI, “Developmental Biology, 6th Edition,” 2000).
For scientists to replicate this effect in humans, they use stem cells, which are also cells that can also differentiate into any type of cell in the body and divide to produce more stem cells. These cells are also known as pluripotent cells since they are capable of developing into several different cell types. However, the blastema that salamanders produce are not completely embryonic. Instead, scientists have found that the cells used for regeneration become slightly less mature versions of the cells they’ve been before (Wired, “Salamander Discovery Could Lead to Human Limb Regeneration,” 07.01.2009). This means researchers don’t have to force adult tissue into becoming pluripotent, making the task a little easier to implement in humans.
The latest development in this field has come from a group of scientists from the University of New South Wales (UNSW), who have designed a new stem cell repair system based on the method used by salamanders to regenerate limbs (UNSW, “Medical scientists develop ‘game changing’ stem cell repair system,” 04.04.2016). According to haematologist John Pimanda, the new technique involves reprogramming bone and fat cells into induced multipotent stem cells (iMS), which can be used to regenerate muscle, bone and cartilage. The team first extract fat cells from the human body, treat them with various growth factors and compounds like 5-Azacytidine (AZA) to turn them into stem cells, and then inject them back into the body to heal tissue. “This technique is a significant advance on many of the current unproven stem cell therapies, which have shown little or no objective evidence they contribute directly to new tissue formation,” stated Pimanda (UNSW).
So far, the new technique has been successful in mice, and human trials are expected to begin by late 2017. But several obstacles still stand in the way. One primary challenge is preventing the cells from becoming cancerous as they go through regeneration. Salamanders typically don’t face the risk of malignant tumors whenever they regenerate tissue, and as stated earlier, the axolotl is in fact 1,000 times more resistant to cancer than mammals, despite how often it regenerates body parts. Right now, Pimanda and his team are making sure that the technique leads to controlled tissue repair and that cell regeneration doesn’t spiral out of control.
With progress being steadily made in regenerating bone and muscle, it may be only a matter of time until we reach the regenerative capabilities of salamanders and have self-repairing organs in the future. A revolutionary development like that would certainly save lives and help all types of patients from those suffering from third-degree burns to those who desperately need an organ donor. Until then, researchers will continue to study salamanders and their incredible regeneration abilities to help guide them towards their goal. Who would have thought that these tiny amphibians could spearhead such miraculous changes in medicine?