Phenotypic Differences in White-Tailed Deer Antlerogenic Progenitor Cells and Marrow-Derived Mesenchymal Stromal Cells

Abstract

Deer antlers are bony appendages that are annually cast and rapidly regrown in a seasonal process coupled to the reproductive cycle. Due to the uniqueness of this process among mammals, we reasoned that a fundamental characterization of antler progenitor cell behavior may provide insights that could lead to improved strategies for promoting bone repair. In this study, we investigated whether white-tailed deer antlerogenic progenitor cells (APC) conform to basic criteria defining mesenchymal stromal cells (MSC). In addition, we tested the effects of the artificial glucocorticoid dexamethasone (DEX) on osteogenic and chondrogenic differentiation as well as the degree of apoptosis during the latter. Comparisons were made to animal-matched marrow-derived MSC. APC and MSC generated similar numbers of colonies. APC cultures expanded less rapidly overall but experienced population recovery at later time points. In contrast to MSC, APC did not display adipogenic in vitro differentiation capacity. Under osteogenic culture conditions, APC and MSC exhibited different patterns of alkaline phosphatase activity over time. DEX increased APC alkaline phosphatase activity only initially but consistently led to decreased activity in MSC. APC and MSC in osteogenic culture underwent different time and DEX-dependent patterns of mineralization, yet APC and MSC achieved similar levels of mineral accrual in an ectopic ossicle model. During chondrogenic differentiation, APC exhibited high levels of apoptosis without a reduction in cell density. DEX decreased proteoglycan production and increased apoptosis in chondrogenic APC cultures but had the opposite effects in MSC. Our results suggest that APC and MSC proliferation and differentiation differ in their dependence on time, factors, and milieu. Antler tip APC may be more lineage-restricted osteo/chondroprogenitors with distinctly different responses to apoptotic and glucocorticoid stimuli.

Deer antler stem cells are a novel type of cells that sustain full regeneration of a mammalian organ—deer antler

“…Previous studies reported that the APCs and PPCs are multipotent in that they can be induced to differentiate into multiple cell lineages, including chondrocytes, osteoblasts, adipocytes, myotubes and neuronal-like cells 23,25 . However, Daley et al 47 reported that antlerogenic progenitor cells (roughly equivalent to RMCs in this study) in white-tailed deer are more lineage-restricted osteo/chondrogenic progenitors, with little adipogenic capacity. These findings are in contrast to those of Rolf et al 23 in fallow deer ( Dama dama ) and Seo et al 25 in sika deer ( Cervus nippon ), wherein the RMCs were readily induced to differentiate into adipocytes.…”

“…In the present study, all three types of the AS cells were induced to differentiate in vitro into chondrocytes, osteocytes and adipocytes. However, we sampled RMCs at the early phase of rapid antler growth but in contrast, Daley et al 47 collected RMCs from the late phase of rapid antler growth; that is, the difference between the two studies may be a function of the timing of tissue sampling. Based on the results of our experiments, we can conclude confidently that the cells from the AS cell lineage are multipotent and that AS cells satisfy the criteria established for stem cells and are therefore, bona fide stem cells.…”

Deer antler stem cell niche: An interesting perspective

“…Several studies indicate that ASCs exhibit molecular traits akin to pluripotent and multipotent stem cells. This is evidenced, for example, by the fact that c-KIT (stem cell factor receptor) and Sca-1 (stem cell antigen-1), recognized markers of embryonic stem cells and tissue-specific stem cells, respectively, have been detected in over 70% of ASCs[ 51 ]. ASCs could be defined as MSCs with embryonic features.…”

The characteristics and medical applications of antler stem cells

“…Interestingly, the differentiation characteristics of ASCs differ depending on the timing of extraction from the antler tip. RMCs taken late in the rapid antler growth phase can only differentiate into osteoblast and chondrocyte lineages [ 49 ]. The reason for the heterogeneity in differentiation potential is unclear and may be because RMCs show progressively more limited differentiation potential as the antler growth phase progresses.…”

“…Notably, although APCs, PPCs, and RMCs show similar marker expressions, differences in the regenerative potential of ASCs from different developmental stages have been reported. For example, RMCs from early and late antler growth sources show significant differences in adipogenic potential [ 49 ]. STRO-1 in ASCs was expressed in the order of APCs (26.3%) < PPCs (53.3%) < RMCs (61.5%) [ 18 ].…”