The Role of Estrogen and the Female Microenvironment in the Sex-related Differences in Muscle Regeneration Exhibited by Muscle-derived Stem Cells

DIFFERENCES IN MUSCLE REGENERATION EXHIBITED BY MUSCLE-DERIVED STEM CELLS *Deasy, B M; *Lu, A; *Weiss, K R; +*Huard, J +*Growth and Development Laboratory, Children’s Hospital of Pittsburgh and Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh PA [email protected] INTRODUCTION Our previous research has shown that male and female postnatal mouse muscle-derived stem cells (MDSCs) display different capacities to regenerate skeletal muscle in vivo [1]. Female MDSCs (F-MDSCs) transplanted into female mice induced significantly better skeletal muscle regeneration than F-MDSCs transplanted into male mice, a finding which suggests that hormonal differences between male and female hosts or the different microenvironments influence the regeneration process. Previous reports have described such sex-related differences in the responses of progenitor and stem cells to hormones [2,3]. We hypothesized that the sex-related differences that we observed in vivo might be caused by different levels of estrogen in the male and female hosts. Estrogen, a potent anabolic hormone, is the major sex steroid found in females. We also hypothesized that exogenous stimulation with 17-beta estradiol, a type of estrogen, might increase the in vivo regeneration exhibited by male MDSCs (M-MDSCs).