On the Phenotype of White-tailed Deer Antlerogenic Progenitor Cells.

Abstract

Repair of large bone defects is one of the key unmet clinical needs in musculoskeletal medicine. A rare exception to the limits of mammalian regeneration is the deer antler, the only example of complete, repeated organ regrowth in an adult mammal. The antlerogenic progenitor cells (APC) at the heart of antler regeneration have the potential to provide tremendous insights into potential strategies for directing adult somatic progenitor cells to achieve large scale tissue repair. As basic questions about the APC phenotype remain unanswered, we embarked on a wide ranging investigation of the properties and behavior of cells from the antlers and marrow of white-tailed deer (Odocoileus virginianus), both in vitro and in an in vivo murine ossicle model. Our findings suggest that antler tip APC are likely more lineage-committed osteo-/chondroprogenitors compared to animal-matched marrow MSC with different, often opposing, responses to glucocorticoid steroids. Moreover, we found that apoptosis, rather than being antagonistic to antler regeneration, may actually contribute to short duration APC homeostasis. We were not able to make definitive statements regarding APC and MSC mechanoresponsiveness. However, our investigation of the effects of oscillatory fluid shear stress uncovered more evidence of the differing effects of substrate on APC growth. In addition, the robust basal production of prostaglandin E2 by APC could contribute to antler-specific behavior. The observed pattern of time, factor, and milieu dependence of APC expansion and differentiation may reflect a system of regulation required to confine antler growth to a specific anatomical and temporal range. Overall, we have demonstrated that APC are mesenchymal stromal cells with a distinctly different phenotype compared to animal-matched bone marrow-derived MSC.