Regeneration is the process by which animals replace tissue or structures after they are lost. Regeneration abilities vary within the Animal Kingdom. For example, many invertebrates such as planarians and hydra can regenerate all of their bodies even after they have been cut into small pieces. Some vertebrates are also capable of complex regeneration. Salamanders and zebrafish are research model systems which regenerate a plethora of body parts, including limbs and heart. However, mammals have limited regenerative ability and in humans and mice it is limited to regeneration of digits in childhood and liver regeneration.
In the wild, it is not uncommon that an animal loses one of its limbs after an encounter with a predator. Most people know about the phenomenon of autotomy, where certain animals such as salamanders lose a part of their bodies (for example the tail) to escape a predator. Autotomy is seen widely across the animal kingdom including lizards and mammals (like skinks and other rodents), but up to now no mammal showed regeneration of the lost structures. Seifert et al (2012) have recently described tissue regeneration in the African spiny mouse (Acomys kempi and Acomys percivalis), which seem to be able to regrow their skin, complete with hair follicles, sweat glands and even cartilage. They have spike-like hair, hence their name, and lose their skin and their tail to escape from predators, such as snakes. They can lose up to 60% of their dorsal skin and within 30 days, the wound will have healed, the hairs will have regrown and there will be no scarring.
The spiny mouse can regenerate a large portion of lost skin scar-free. Seifert et al. (2012)
Seifert et al found that the propensity for their skin to tear was due to its low tensile strength. They found that the spiny mouse skin was 20 times weaker than common mouse skin, and that common mouse skin requires 77 times more energy to break than spiny mouse skin. They investigated the anatomy of the skin further, to see whether differences between this and the common mouse skin are responsible for the weakness. They found that the spiny mouse skin is anatomically similar to the common mouse skin, but that it has larger hair follicles. Perhaps surprisingly, they found no evidence of a fracture plane, as is the method of autotomy in geckos and skinks. Seifert et al reason that because the spiny mice have larger hair follicles, a lower amount of connective tissue in the skin may be the reason for the reduced tensile strength and elasticity.
The unusual features of their skin accounts for the ease with which the spiny mouse loses its skin and escapes predators. But it does not explain how the animals survived or how they regenerated so effectively. After the scientists produced a 4mm wound on their backs, the spiny mice manage to re-epithelize their wound within 3 days, whereas the common mice fail to do it so quickly. They do this by an increase contraction rate of the skin around the wound with respect to the common mice. This reduces the effective wound size. It is also notable that the spiny mouse heals scar-free, with the collagen type III (rather than collagen type I in the common mouse) rearranging in a pattern similar to the surrounding dermis. It seems that rapid repithelisation and high wound contraction are key, as well as a slow deposition of wound ECM, in a porous configuration and comprising mainly of type III collagen, in preventing fibrosis and encouraging regeneration of the skin, as opposed to fibrosis and scar formation, without regeneration. Examination of folliculargenesis showed normal pelage hairs as well as large spiny hairs in the wound. They found a highly proliferative, localized population of epidermal cells driving follicle regeneration, in a similar way that they work during development.
In all, this study suggests that mammals do have the right tools available for regeneration, at least of the skin. This is incredibly encouraging to regeneration researchers such as myself, and reminds us that basic research of the mechanisms governing regeneration is crucial. Most of regeneration research is performed on salamanders, fish and invertebrates, because it is difficult to work on a model that doesn’t regenerate. Mice are also a very popular model organism; the mrl mouse (KO for p21) is incredibly interesting, but it is an artificial model, with only limited regenerative ability compared to the spiny mouse. There are numerous advantages to working with the current models for regeneration (including fast regeneration, easy to keep animals, very robust regenerative abilities, can regenerate a lot more than the just skin, etc) but it would be informative to compare how nature has solved the intricacies of regeneration in mammals, if at all. Although its regeneration abilities are quite limited compared to some of the currently used model organisms in regeneration, the spiny mouse could become a very important model to study wound healing and skin regeneration, to help find a solution to chronic wounds that don’t heal. This paper also reminds us of the importance of studying the world around us, in search for ways in which nature has already found the answer to some of our questions. It also stresses the importance of crosstalk in science and collaboration among scientists, without which a molecular biologist from the US would not have known to go searching for a little regenerating mouse in Africa.