Substances for regenerative wound healing during antler renewal stimulated scar-less restoration of rat cutaneous wounds

Scarification is the outcome of cutaneous wound healing under normal conditions. Although considerable effort has been expended in this field, scar-less healing has not been achieved satisfactorily. The lack of a good model of scar-free healing has contributed to this undesirable situation. However, the annual regeneration of deer antlers, which starts from regenerative wound healing over the top of the pedicles (permanent bony protuberances), may provide such a model. Therefore, in this study, we investigated the process of pedicle wound healing at the organ, tissue, cell, and molecular levels. Our results convincingly demonstrate that wounds over the pedicle preceded a regenerative healing process including regeneration of skin appendages, such as hair follicles. Compared to the scar healing in rats, regenerative healing of the pedicle wound exhibited a weaker inflammatory response, lack of myofibroblast induction, and higher ratios of Col III/Col I, TGF-β3/TGF-β1, and MMP/TIMP. Importantly, our periosteal transplantation experiments in vivo revealed that this regenerative healing process was achieved through induction of antler stem cells (ASCs). Further study showed that this effect of ASCs on regenerative healing was not species-specific but more generic and could be applied to other mammalian species, as injection of ASCs stimulated regenerative healing of full-thickness excisional cutaneous wounds in rats. Overall, our findings show that ASCs may have therapeutic potential in enhancing the quality of wound healing and preventing scar formation in clinical settings.