Arthropods, how these 4 animals can regenerate and why humans can not ,meaning all animals with jointed limbs and segmented bodies, have long been known to be able to regrow legs and arms after loss, according to Gerhard Scholz, a comparative zoologist at the Humboldt University of Berlin. For example, when crustaceans are attacked they can even break their injured leg themselvesand sacrifice it to survive.
And a growing body of research into the molecular mechanisms behind regeneration seems to suggest that there is no universal return.
“There are actually multiple methods that nature uses to regenerate complex structures, and there is some variation across the animal kingdom,” says Catherine McCusker, professor of molecular mechanisms of regeneration at the University of Massachusetts, Boston. They differ between vertebrates and invertebrates, but also between these categories.
1. Planarian and the stem cell method
A planarian parasite (flatworm) under a microscope. (Credit: Rattiya Thongdumhyu/Shutterstock)
Take for example the flatworm, also known as a planaria and one of the most impressive examples of regeneration in the animal kingdom. These aquatic worms are invertebrates and can completely regenerate their entire body even after losing up to 90 percent of yourself. If they are decapitated, their heads may even grow back.
“These guys are actually using a ‘stem cell-mediated method’ of regeneration,” says McCusker. “They have a pluripotent stem cell population that’s just hanging around in the body [times] and sporadically replaces damaged cells. When a major amputation occurs, these cells are essentially called upon to regenerate the missing structure, whatever it is. Sea animals called sea sprays use the same technique as well.
2. Axolotl and the method of dedifferentiation
Axolotl (Ambystoma mexicanum) in front of a white background. (Credit: Eric Isselee/Shutterstock)
While the Planarian is impressive for its regenerative abilities, the real regeneration MVPs seem to be the Axolotl, the adorable Mexican water salamander. It is the only vertebrate that can regenerate different parts of his body no matter how old he is. It can replace entire missing limbs, tail, testicles, internal organs such as intestines and heart, spinal cord and even neurons and part of the brain.
The axolotl does not tap into its stem cell population, but instead uses a technique known as dedifferentiation. After being injured, they grow a tiny cell called a blastema from nearby undifferentiated cells.
Read more: What the axolotl’s limb regeneration abilities have to teach us
“What they’re doing is they’re essentially turning back the clock on these old cells in your body to start behaving like embryonic cells, right, but they’re not stem cells,” McCusker says. “They’re kind of in between stem cells and like adult cells, so they’re not differentiated, but they know what they’re going to be.”
That’s what it’s called epimorphic regeneration and it is the technique of choice for many other animals that have the ability to regenerate. Ground lizards and salamanders also use this technique.
The starfish tooand in some cases a whole new body can grow from just one hand.
3. Hydra is a rearrangement, also known as Morphallaxis
Hydra is a genus of small freshwater animals of the phylum Cnidaria and class Hydrozoa. (Credit: Choksawatdikorn/Shutterstock)
A hydra is a freshwater jellyfish-like organism that likes to stick to rocks and looks somewhat like an anemone – they are true jack-of-all-trades. In most cases, they go through a process that is known as morphalaxis.
“Essentially what it does is they take whatever is left in the tissue and they just move the cells around, reorganize them so that you get a perfectly formed mini-version with all the right structures,” says McCusker.
But they can also combo. “Depending on how they’re injured can change how they regenerate,” says McCusker.
If injured more intensely, they will also engage in the same process that the Axolotl does, with a new set of cells growing to replace the missing structure through cell proliferation and dedifferentiation.
4. Zebra fish also as combinations
Zebrafish (Credit: Horvath82/Shutterstock)
Zebrafish can regenerate even into adulthood, everything from the fins to the spinal cord, retina, heart, kidneys, and the most highly developed forebrain, the telencephalon — but they also like combinations because the mechanisms that enable regeneration seem to be specific to each organ. Fin regeneration looks similar to an axolotl or starfish. But telencephalon regeneration requires stem cells to save the day, just like the flatworm.
Why do people fail to regenerate?
Why can these animals regenerate? And animals, like us and other mammals, are bad at regenerating? This is still a puzzling question today, according to Andrey Elchaninov, head of the Regenerative Medicine Laboratory at Vladimir Kulakov Medical Center. To this day, there are various conflicting hypotheses and the scientific jury is still out.
Elchaninov’s favorite theory is the one related to the evolution of our immune system. “If immunity is very high, as in mammals or birds, those species cannot regenerate legs, toes, etc. Why so?” says Elchaninov.
Perhaps because the immune system wants to prevent tumors, and the molecular mechanisms for regeneration are similar to those in tumor formation – for example, with the help of stem cells.
“So evolution chose, ‘Okay, these species will be less likely to have tumors, but they won’t regenerate,'” Elchaninov says.
This theory is supported by research on the African spiny mouse, a species of mouse that can regenerate its skin and fur after injury. Studies show that they don’t seem to have any macrophages, a type of immune cell, on the skin they regenerate.
“There are no macrophages in the skin of the trauma. Therefore, I think that there is some connection between immunity and regeneration”, says Elchaninov.
Advances in research into exactly how and why some animals can regenerate and others cannot will shed light on whether humans could ever take advantage of some of these abilities. This is of particular interest to doctors, scientists and professionals working in the field of regenerative medicine.
“For example, humans cannot regenerate fingers or feet, but in prenatal development we have all the genes that contributed to the growth of feet or fingers, 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 in postnatal development as well and regenerate limbs.”
“But that will be in the future,” says Elchaninov. “Far, far in the future I think.”