Deer antler renewal gives insights into mammalian epimorphic regeneration

Abstract Deer antlers are the only known mammalian organ that, once lost, can fully grow back naturally. Hence, the antler offers a unique opportunity to learn how nature has solved the problem of mammalian epimorphic regeneration (EpR). Comprehensive comparisons amongst different types of EpR reveal that antler renewal is fundamentally different from that in lower vertebrates such as regeneration of the newt limb. Surprisingly, antler renewal is comparable to wound healing over a stump of regeneration-incompetent digit/limb, bone fracture repair, and to a lesser extent to digit tip regeneration in mammals. Common to all these mammalian cases of reaction to the amputation/mechanical trauma is the response of the periosteal cells at the distal end/injury site with formation of a circumferential cartilaginous callus (CCC). Interestingly, whether the CCC can proceed to the next stage to transform to a blastema fully depends on the presence of an interactive partner. The actual form of the partner can vary in different cases with the nail organ in digit tip EpR, the opposing callus in bone fracture repair, and the closely associated enveloping skin in antler regeneration. Due to absence of such an interactive partner, the CCC of a mouse/rat digit/limb stump becomes involuted gradually. Based on these discoveries, we created an interactive partner for the rat digit/limb stump through surgically removal of the interposing layers of loose connective tissue and muscle between the resultant CCC and the enveloping skin after amputation and by forcefully bonding two tissue types tightly together. In so doing partial regeneration of the limb stump occurred. In summary, if EpR in humans is to be realized, then I envisage that it would be more likely in a manner akin to antler regeneration rather to that of lower vertebrates such as newt limbs.