New physiological insights into the phenomena of deer antler: A unique model for skeletal tissue regeneration

Generally, mammals are unable to regenerate complex tissues and organs however the deer antler provides a rare anomaly to this rule. This osseous cranial appendage which is located on the frontal bone of male deer is capable of stem cell-based organogenesis, annual casting, and cyclic de novo regeneration. A series of recent studies have classified this form of regeneration as epimorphic stem cell based. Antler renewal is initiated by the activation of neural crest derived pedicle periosteal cells (PPCs) found residing within the pedicle periosteum (PP), these PPCs have the potential to differentiate into multiple lineages. Other antler stem cells (ASCs) are the reserve mesenchymal cells (RMCs) located in the antlers tip, which develop into cartilage tissue. Antlerogenic periosteal cells (APCs) found within the antlerogenic periosteum (AP) form the tissues of both the pedicle and first set of antlers. Antler stem cells (ASCs) further appear to progress through various stages of activation, this coordinated transition is considered imperative for stem cell-based mammalian regeneration. The latest developments have shown that the rapid elongation of the main beam and antler branches are a controlled form of tumour growth, regulated by the tumour suppressing genes TP73 and ADAMTS18. Both osteoclastogenesis, as well as osteogenic and chondrogenic differentiation are also involved. While there remains much to uncover this review both summarises and comprehensively evaluates our existing knowledge of tissue regeneration in the deer antler. This will assist in achieving the goal of in vitro organ regeneration in humans by furthering the field of modern regenerative medicine. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: As a unique stem cell-based organ regeneration process in mammals, the deer antler represents a prime model system for investigating mechanisms of regeneration in mammalian tissues. Novel ASCs could provide cell-based therapies for regenerative medicine and bone remodelling for clinical application. A greater understanding of this process and a more in-depth defining of ASCs will potentiate improved clinical outcomes.