Abstract：Deer antlers are the only mammalian organs that can fully grow back once lost from their pedicles, the permanent bony protuberances. Studies have demonstrated that it is the proliferation and differentiation of pedicle periosteal cells (PPCs) that give rise to the antler blastema, from which antler regeneration takes place. PPCs express key embryonic stem cell markers and can be induced to differentiate into multiple cell lineages in vitro, so are called antler stem cells. Further studies have found that PPCs can initiate antler regeneration only when they have interacted with the pedicle skin. Histologically, the process of early antler regeneration resembles that of healing of a mouse (Mus musculus) leg stump wound. However what sets these two apart is the difference in proliferation potential between the PPCs and the periosteal cells of the mouse long bone. We believe that if we can impart a greater proliferation potential to the long bone periosteal cells, we might be able to achieve the dream of regenerating limbs in mammals including humans. This article has reviewed the progress on histogenesis of antler regeneration including the inner and outer tissue components and antler stem cell research, made comparison between regenerations of deer antlers and newt limbs and identified their similarities and differences, pointed out the future direction toward the possible use in clinics, and provides new way of thinking for how to ultimately solve the problem of human limb regeneration.
