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Scrutinizing salamanders to study scarring in humans

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GAINESVILLE, Fla. — The axolotl, a type of salamander, can regenerate lost limbs, regrow its own spinal cord and dodge cancer — which is why University of Florida researchers have created the tools to study how the axolotl’s blood works to heal itself, according to a study published online recently in the journal Blood. Axolotls have extraordinary regenerative properties, said Ed Scott, Ph.D., a UF Health researcher and a professor in the UF College of Medicine department of molecular genetics and microbiology. He is using axolotls to study how humans might heal without scars after surgery. “When axolotls are young and still living together in nature, it seems like their favorite snack is their siblings’ appendages,” Scott said. “They just nibble them off and they grow right back. They don’t even know they were missing.” To study blood at the site of regeneration, researchers are examining green axolotls developed to have fluorescent red blood and red axolotls developed to have green blood. The researchers can follow the contrasting blood color to the site of regeneration and pull blood cells from that site to study what kind of healing proteins are present. Axolotls also seem unable to develop cancer. In the 1940s and 1950s, papers were published examining what happened when axolotls were exposed to carcinogens, Scott said. They grew an extra arm or leg but never developed cancer. Mammals can, of course, develop cancer, and lose their ability to regenerate as they age, Scott said. “In human beings, they can do in-utero surgeries on growing babies and the babies are born without scars. When kids are very, very young, they can cut their finger back to the first knuckle and it will grow back,” Scott said. “But by the time you’re an adult, if you get down to the nail bed, that’s where regeneration stops.” In all animals, blood is responsible for repairing the body, Scott said. Red cells carry oxygen and nutrients to cells, whereas white blood cells monitor and repair damaged cells. In mammals, proteins in the blood help injuries scab and scar over very quickly, said Malcolm Maden, Ph.D., a professor in the department of biology. This is beneficial: It keeps mammals from dying from infection, Maden said. “There’s something different about the blood cell formation in axolotls,” Maden said. “They’re obviously healthy creatures living in fungus- and bacteria-infested waters. So they must have a different way of keeping the nasty things at bay while they are healing.” Usually a speckled, brown-green color, the axolotl used in research is a naturally occurring mutant with white skin. Their internal organs — and, in this case, blood — can be visible, making the study of regeneration much easier. “You can see all the green cells zooming to the site of damage, and then ask, ‘Is this a special population of blood cells that accumulate here?’” Maden said. “Thanks to having green blood in a white animal, now you can observe the blood cells taking part in the process of wound healing, then pluck them out, purify them and understand what’s going on much better than you could before.” Scott said axolotls, mice and humans all share similar cells, but the cells behave differently. “Maybe the axolotls are expressing different genes in healing in a different pattern, and that might make all the difference between scarring and regeneration,” Scott said. “In this way, we have two animals — axolotls and mice — that have very similar genes and cells, and now we can just directly compare them. It becomes one of those old Hocus Focus comics where you have to find the differences. Maybe those differences are key differences for regeneration.” Next, the researchers hope to study why diseases such as cancer don’t spread in the axolotl.
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