Stromal cell-derived factor-1 accelerates bone regeneration through multiple regenerative mechanisms

Abstract

ObjectiveStem cell transplantation has become a popular and promising therapeutic approach for many clinical conditions. Engrafted mesenchymal stem cells (MSCs) can promote bone regeneration in both humans and model animals; however, the differentiation and survival rates of the engrafted MSCs are reported to be poor. We hypothesized that MSCs promote bone regeneration primarily through paracrine mechanisms. SDF-1 is a factor secreted from MSCs that is known to be involved in cell-recruitment and angiogenesis. In this study, we examined the bone-regenerating activity of SDF-1 in the rat calvarial bone defect model. MethodsCollagen sponge containing SDF-1 was transplanted into the rat calvarial bone defect. The effects of treatment were examined both histological and microcomputed tomography analysis. The effects of SDF-1 on cellular migration and proliferationin vitro were assessed by transwell and WST-assay, respectively. ResultsSDF-1 significantly enhanced the bone regeneration in rat calvarial bone defect model. SDF-1 promoted the recruitment of endogenous MSCs/osteogenic progenitors and promoted angiogenesisin vivo. Furthermore, SDF-1 directly enhanced the cell-migration activity of human bone marrow MSCs (hBMMSCs), human umbilical vein endothelial cells (HUVECs), and rat calvarial periosteum cells (rCPCs), without affecting their proliferative activities, in vitro. ConclusionsOur findings suggest that the local administration of SDF-1 enhances bone regeneration by inducing multiple endogenous tissue-regenerating activities.