When Marvel Comics created a short superhero who could heal horrific injuries, perhaps instead of “Wolverine”, they should have named him “African spiny mouse”. These tiny rodents can jettison strips of skin from their own hides when captured by predators, and heal those same wounds with extraordinary speed.
Healing powers are common in the animal world. Salamanders and starfish can regrow lost limbs, while some flatworms can regenerate their bodies from a single cell. But mammals lag behind – while some species can grow back a lost tail, when most of us lose our body parts, we do so permanently. The spiny mice are an exception.
Biologists have noted that these rodents have very weak skin, which seems to slough off easily when they are handled. Led by these anecdotal reports, Ashley Seifert from the University of Florida has studied the skin-shedding ability in greater depth, focusing on two species: Kemp’s spiny mouse (Acomys kempi); and Percival’s spiny mouse (Acomys percivali).
As a first line of defence, the mice have stiff hairs on their backs that act like a hedgehog’s spines. But if they are caught, they struggle vigorously and quickly lose strips of skin. It’s a dramatic strategy. The mice end up with large open wounds, and can lose up to 60 percent of the skin along their backs.
Back in the lab, Seifert discovered why. The spiny mouse’s skin looks superficially similar to that of an ordinary house mouse, but it contains a far greater proportion of follicles—the cradles that hairs grow from—and their associated glands. As a result, they also have less connective tissue, and their skin tears under the smallest forces. For comparison, a house mouse’s skin is around 20 times stronger than a spiny mouse’s, and can absorb 77 times more energy before breaking.
For most mammals, this would be a disaster. The spiny mouse must have some way of controlling infections, and Seifert is now studying its immune system to discover its secrets. But he has already found that it complements its weak skin with extremely fast healing. Its wounds stop bleeding, scab over quickly, and shrink by 64 percent within a day. While a rat would take 5 to 7 days to completely cover a wound with new skin, a spiny mouse can do it in just 3.
And rather than laying down fresh collagen fibres in dense parallel layers, like other mammals do, the spiny mouse deposits its collagen in loose basket-weave networks that resemble those of the original tissue. The result: scar-free regeneration.
The spiny mice can also close relatively large holes in their ears. Ear-holes are a standard type of injury used by scientists who study wound repair (or, indeed, people who want to wear earrings!). Most mammals completely fail to seal such injuries, with rabbits being an exception. But spiny mice not only heal ear holes, but they’ll re-grow the different layers of skin, hair follicles, fat cells, muscles and cartilage. Within weeks, their ears are as good as new, and scar-free.
When a salamander loses its leg, it begins the healing process by transforming some of the cells in the stump into a “blastema” – a mass of dividing uncommitted cells. These cells lose their specialised adult traits and revert to a more embryonic stem-like state, where they’re capable to producing the various tissues of the lost limb. The blastema stays in this regenerative state thanks to signals from the “wound epidermis”, a special layer of skin that forms above it. If either the blastema or the wound epidermis fails to form, the limb won’t grow back.
Seifert found that spiny mice appear to heal their wounds in a similar way. When their ears are punctured, they develop a ball of cells that many of the molecular hallmarks of a salamander’s blastema.
This suggests that mammal regeneration may not be as out-of-reach as we thought. “One of the major hurdles to human regeneration of say, a digit, is the formation and maintenance of a blastema,” says Seifert. “The hope is that we can use regeneration of ear tissue in [spiny mice] to better understand how a blastema can form in a mammal.” If this first step falls into play, it could be that regeneration will just happen on its own.
“With regards to human applications we will have to wait and see,” says Seifert. In the meantime, he feels that the spiny mice show how important it is to look beyond the typical “model animals” that biologists focus on. For example, salamanders, newts and flatworms are the stars of regeneration science, but more because it’s convenient to work with them than because they’re the most relevant creatures for our own biology. The spiny mice may provide important clues for human medicine that more distantly related regenerating animals cannot.
Reference: Seifert, Kiama, Seifert, Goheen, Palmer & Maden. 2012. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature http://dx.doi.org/10.1038/nature11499