Abstract
Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.
Highlights
Steroid-induced osteonecrosis of the femoral head (ONFH) is caused by long-term glucocorticoid use
An earlystage rat model of steroid-induced ONFH was established by using lipopolysaccharide combined with methylprednisolone which has been proved to be effective in modelling ONFH [13,14,15], and the therapeutic effect of exosomes derived from hypoxia-preconditioned Bone marrow mesenchymal stem cells (BMMSCs) on steroidinduced ONFH in rats was studied
We investigated the effects of hypoxia preconditioning on the biological properties of BMMSCs
Summary
Steroid-induced osteonecrosis of the femoral head (ONFH) is caused by long-term glucocorticoid use. Recent animal studies have shown that exosomes have therapeutic effects in steroid-induced ONFH. Guo et al demonstrated that exosomes derived from human synovial-derived mesenchymal stem cells could prevent steroid-induced ONFH in a rat model [5]. Liu et al studied the effects of exosomes derived from human-induced pluripotent stem cell-derived mesenchymal stem cells in steroidinduced ONFH and they got similar results [6]. In a mouse model of femoral fracture, they demonstrated that exosomes derived from MSCs cultured under hypoxia exhibited greater therapeutic effects on bone fracture healing. Whether exosomes derived from hypoxiapreconditioned BMMSCs could exhibit better therapeutic effects on steroid-induced ONFH was unclear. Based on the above findings, we hypothesized that exosomes derived from BMMSCs cultured under hypoxia might exhibit increased proangiogenic ability and protective effect on steroidinduced ONFH. An earlystage rat model of steroid-induced ONFH was established by using lipopolysaccharide combined with methylprednisolone which has been proved to be effective in modelling ONFH [13,14,15], and the therapeutic effect of exosomes derived from hypoxia-preconditioned BMMSCs on steroidinduced ONFH in rats was studied
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