Effect of the Host on Cellular Therapies for Bone Healing

Muscle-derived stem cells (MDSCs) have been isolated from murine skeletal muscle and have the ability to differentiate into osteogenic, myogenic and chondrogenic lineages, among others. MDSCs may prove to be an attractive cell sources for orthopaedic tissue engineering therapies. However, MDSCs must prove successful in many patient populations before clinical translation becomes a reality. MDSCs have been characterized and studied extensively based on attributes of the donor animal. To date, little is known about the effect of the host animal or surrounding tissue environment on MDSC therapies. These studies were undertaken to determine the efficacy of MDSCs in bone formation and bone healing in different hosts, representing different patient groups. MDSCs are known to exhibit sexual dimorphism, by donor sex, of osteogenic differentiation. Therefore, MDSC-mediated ectopic bone formation and cranial bone defect healing were compared between male and female host animals. Castrated male and ovariectomized female hosts were also examined in MDSC-mediated ectopic bone formation and cranial bone defect healing studies, in order to determine the role of host sex hormones in MDSC osteogenic therapies. Moreover, castrated males and ovariectomized females represent aged hosts, as these animals exhibit some aging symptoms related to loss of sex hormones. Lastly, MDSCs have only previously been applied to freshly created defects, so a delayed application study was carried out to determine if MDSCs could heal established defects. MDSCs were applied to a cranial defect, which had been previously created and allowed to fill with scar-like fibrous tissue, to determine the efficacy of MDSCs in unfavorable bone defect environments or as treatment for non-unions. The results of these studies helped to elucidate the effect of host animal and tissue environment on MDSC-mediated bone tissue engineering therapie