Osteogenic Potential of Postnatal Skeletal Muscle–Derived Stem Cells Is Influenced by Donor Sex

Abstract

When stimulated with BMP4, both F- and M-MDSCs underwent osteogenic differentiation, although M-MDSCs had a significantly greater ALP activity and a larger increase in the expression of osteogenic genes than F-MDSCs. In the pellet culture assay, M-MDSCs showed greater mineralization than F-MDSCs. BMP4 stimulation of single cell-derived colonies from M-MDSCs showed higher levels of ALP than those from F-MDSCs. Similar results were obtained with the MDSC-BMP4 cells. In vivo, F-MDSC-BMP4 cells displayed variability in bone area and density, whereas M-MDSC-BMP4 cells showed a more consistent and denser ectopic bone formation. More bone formation was also seen in male hosts compared with female hosts, regardless of the sex of the implanted cells. These results suggest that M-MDSCs may contain more osteoprogenitor cells than F-MDSCs, which may have implications in the development of cellular therapies for bone healing.