Green anole lizards can regenerate their tails after injury, an ability that could inform treatments for people.Credit: Wolfgang Kaehler/LightRocket via Getty
After an injury, some flatworms can regrow almost every cell in their bodies, axolotls can rebuild entire limbs and parts of their brain, zebrafish can mend broken spinal cords and green anole lizards can fabricate new tails.
Most mammals are incapable of the restorative feats seen in fish, amphibians, reptiles and worms, whose abilities have long fascinated researchers. Now scientists are taking what they have learnt from these animals and are applying that knowledge to human cells, thanks to advances in genomics, proteomics and imaging at the level of the single cell.
“There’s a big push right now to exploit super-healing species and to try to see how quickly we can translate those findings,” says Albert Almada, a stem-cell biologist at the University of Southern California in Los Angeles.
Several research teams presented their latest findings at the International Society for Stem Cell Research meeting in Hong Kong last week.
Zebrafish spines
A zebrafish (Danio rerio) with a severed spinal cord can go from being paralysed to moving fluidly in eight weeks. Mayssa Mokalled, who studies tissue regeneration and stem-cell biology at Washington University in St. Louis, Missouri, and her colleagues have identified a population of cells in the zebrafish that are important for this recovery — and these cells are similar to human fetal astrocytes. After an injury, astrocytes create a protective barrier around the damaged site, but can also inhibit neuronal repair.
Mokalled and her colleagues looked for molecules involved in the activation of the cells that induce regeneration in zebrafish. When the team introduced the same molecules into human astrocytes, the cells started to look and behave more like those of the zebrafish. In preliminary studies in which the researchers transplanted the transformed human cells into mice, the cells seemed more effective at creating the protective barrier, but the inhibitory post-injury response was reduced. “I would love to see this go all the way to therapy,” says Mokalled.
Lizard tails
But the evolutionary distance between zebrafish and humans is wide. Almada is instead looking at the green anole lizard (Anolis carolinensis). Lizards are the closest living relative to humans that is able to regenerate an entire appendage. Humans and lizards share many of the same genes. “We think it’ll be more translatable to human biology, because they have a lot of the same machineries at the DNA level,” says Almada.
At the conference, Almada described how a population of muscle stem cells in lizards regenerates the animal’s tail. The cells are similar to those found in mice and humans, except that the lizard version can make muscle tissue from scratch, which the mouse and human versions cannot, he says. Almada hopes to work out how the lizard cells achieve this feat and eventually apply that to muscle growth in humans to treat degenerative muscular diseases, strengthen muscles in older people and treat wounds.
