For years biologists have studied salamanders for their ability to regrow lost limbs. But amphibian biology is very different than human biology, so lessons learned in laboratories from salamanders are difficult to translate into medical therapies for humans. New research in the Sept. 27 issue of the journal Nature describes a mammal that can regrow new body tissues following an injury. The African spiny mouse could become a new model for research in regenerative medicine.
“The African spiny mouse appears to regenerate ear tissue in much the way that a salamander regrows a limb that has been lost to a predator,” said Ashley W. Seifert, a postdoctoral researcher in UF’s biology department. “Skin, hair follicles, cartilage — it all comes back.”
African spiny mouse specimen collected in the field near Nairobi Kenya.
Nature - Skin shedding and tissue regeneration in African spiny mice (Acomys)
A. kempi and A. percivali exhibit skin autotomy and subsequent rapid healing. a, b, A. kempi (a) and A. percivali (b) possess stiff, spine-like hairs on the dorsum. c, A. kempi after loss of dorsal skin. d, e, Scab formation after full-thickness skin injury visible at D3 (d). The same wounds in d are no longer visible
The spiny mouse also regrows tissue on its main body when injured but not as completely as it does in its ears. “On their backs, they regrow hair follicles and skin, but the muscle beneath the skin doesn’t regenerate,” Seifert said.
Seifert was studying scar-free healing in amphibians when a colleague told him that a small rodent he had observed in Africa seemed capable of autotomy, a defense mechanism whereby the animal self-amputates a body part to escape a predator.
“Autotomy in skinks, geckos and some salamanders is well known,” Seifert said. “But it is very rare in mammals, and so far we’ve only seen it in a few rodents that can jettison their tail.”
Seifert’s colleague said that the African spiny mouse appeared to have tear-away skin that allowed it to slip a predator’s grasp. The notion was interesting enough to send Seifert packing to the Mpala Research Centre near Nairobi, Kenya.
In Nairobi, Seifert was able to document the first known case of skin autotomy in a mammal. But it was how the animals’ injuries appeared to be healing that really got his attention.
Seifert used a 4mm biopsy punch, about the size of a large BB, to puncture holes in the ears of the mice to see if the animal showed regenerative capabilities.
“The results were astonishing,” he said. “The various tissues in the ear grew back through formation of blastema-like structures — the same sort of biological process that a salamander uses to regenerate a severed limb.”
Ken Muneoka, a Tulane University professor of cell and molecular biology who was not involved with the study, agrees that Seifert’s findings are important.
“It could represent a new model system for skin wound healing and tissue regeneration in humans,” he said.
Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells4) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.
Acomys regenerates hair follicles, sebaceous glands, dermis, adipose tissue and cartilage in 4-mm ear punches. a, A regenerated 4-mm ear punch in A. percivali. b, Unwounded tissue in Acomys ear pinna. c, Regenerated dermis, hair follicles, cartilage and adipose tissue within biopsy punched area. White circle denotes the original punch area.
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