It’s been long known that arthropods, meaning all animals with articulated limbs and bodies with segments, can rebuild legs and arms after a loss, according to Gerhard Scholtz, a comparative zoologist at Humboldt University Berlin. For instance, when crustaceans are attacked they can even break off their injured leg themselves, and sacrifice it to survive.
Now, the eight-legged sea spider Pycnogonum litorale — think of a marine creature related to terrestrial arachnids like spiders, scorpions and mites — has shown that anthropods can recover entire parts of their body, too. In a recent study published in Proceedings of the National Academy of Sciences, Scholtz’s team ran experiments amputating various body parts of 23 specimens of sea spiders. Much to the scientists’ surprise, the majority of the young and adolescent spiders could carry out near-complete regeneration of all of their missing body parts.
“To regenerate things along the body axis, this was unknown, and there was kind of like a dogma saying anthropods weren't able to do that,” says Scholtz. “But we have shown that it is possible. It was unexpected. It was a big surprise.”
Exactly how sea spiders are pulling off this feat is still unclear, though. In fact, a growing body of research into the molecular mechanisms behind regeneration seems to suggest that there’s no one-size-fits-all come-back.
1. Planarian and the Stem Cell Method
Take the flatworm, for example, also known as Planarian and one of the most impressive examples of regeneration in the animal kingdom. These aquatic worms are invertebrates, and can completely regenerate their entire bodies even after losing up to 90 percent of themselves. If they’re beheaded, they can even grow their head back.
“Those guys actually use a ‘stem cell mediated method’ of regenerating,” says Catherine McCusker, a professor of molecular mechanisms of regeneration at University of Massachusetts, Boston. “They have a pluripotent population of stem cells that just hangs out in the body at all [times] and is sporadically replacing damaged cells. When a big amputation happens, those cells are essentially called upon to regenerate the missing structure, no matter what it is.” Marine animals called sea squirts use this same technique, too.
2. Axolotl and the Dedifferentiation Method
Whilst the Planarian is impressive in its regenerative abilities, the real MVPs of regeneration seem to be the Axolotl — the adorable Mexican water salamander. It is the only vertebrate that can regenerate various of its body parts no matter how old it is. It can replace entire missing limbs, its tail, its testes, its internal organs like the gut and heart, its spinal cord and even its neurons and part of its brain.
The Axolotl doesn't tap into its stem cell population though, instead, it uses a technique known as dedifferentiation. Once they’re injured, they grow a stub called the blastema from nearby undifferentiated cells.
Read More: What the Axolotl's Limb-Regenerating Capabilities Have to Teach Us
“What they do is they essentially turn the clock back in these old cells in their body to start to behave like embryonic cells, right, but they aren’t stem cells,” says McCusker. “They're kind of somewhere in between a stem cell and like an adult cell, so they’re not differentiated, but they know what they're going to be.”
This is called epimorphic regeneration and it’s a technique of choice for many other animals who have the ability to regenerate. Terrestrial lizards and salamanders also use this technique.
The starfish does too, and in some cases it can grow an entirely new body from just a single arm.
3. Hydra is Reshuffling, aka Morphallaxis
The hydra is a freshwater jellyfish-like organism that likes to stick to rocks and looks somewhat like an anemone — they’re real jacks of all trades. In most cases, they undergo a process that’s known as morphallaxis.
“Essentially, what that does is that they take whatever's remaining in the tissue, and they just shuffle the cells around, reorganize them, so that makes a perfectly formed mini-version with all of the appropriate structures,” says McCusker.
But, they can also do a combo. “Depending on how they're injured can flip the mode of how they regenerate,” says McCusker.
If they’re injured more intensely, they’ll also tap into the same process that the Axolotl does, with a new pool of cells growing to replace the missing structure through cell proliferation and dedifferentiation.
4. Zebrafish Like Combos, Too
Zebrafish can regenerate, even in their adult age, everything from fins to spinal cord, retina, heart, kidneys and the most highly-developed front part of the brain, the telencephalon — but they like combos too, because the mechanisms that allow for regeneration seem to be organ-specific. Fin regeneration looks similar to the Axolotl or the starfish. But regeneration of the telencephalon calls on stem cells to save the day, just like the flatworm.
Why Do Humans Suck at Regenerating?
Why is it that these animals can regenerate? And animals, like us and other mammals, are lousy at regenerating? That’s still a puzzling question today, according to Andrey Elchaninov, the head of the Laboratory of Regenerative Medicine at the Vladimir Kulakov National Medical Research Center. To this day, thereare various clashing hypothesis, and the scientific jury is still out.
Elchaninov’s favorite theory is one tied to the evolution of our immune system. “If immunity is very high, like in mammals or birds, these species cannot regenerate legs, fingers and so on. Why is that?” Elchaninov says.
Maybe it’s because the immune system wants to prevent tumors, and the molecular mechanisms for regeneration are similar to that of tumor formation — for example, using stem cells.
“So, evolution chose ‘Okay, these species will be less likely to have tumors, but they will not regenerate,’” says Elchaninov.
This theory is supported by research on the African spiny mouse, a type of mouse that can regenerate their skin and fur after an injury. Studies show they don’t seem to have any macrophages, a type of immune cell, on the skin they regenerate.
“There are no macrophages in the trauma skin. That's why I think is there is some connection between immunity and regeneration,” Elchaninov says.
Progress in research on exactly how and why some animals can regenerate and others cannot, will shine a light on whether humans could ever tap into some of these abilities. This is of specific interest for doctors, scientists and professionals working in the field of regenerative medicine.
“For example, humans cannot regenerate fingers or legs, but in prenatal development we have all genes that contributed to leg-growth or finger-growth, and these are actually the same genes found in starfish and Hydra,” says Elchaninov. “Maybe there will be a way to ‘wake up’ these genes also in postnatal development, and regenerate limbs.”
“But this would be in the future,” Elchaninov says. “Far, far in the future, in my opinion.”