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

Objective: Stem 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. Methods: Collagen 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. Results: SDF-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. Conclusions: Our findings suggest that the local administration of SDF-1 enhances bone regeneration by inducing multiple endogenous tissue-regenerating activities.