Stromal cell-derived factor-1 enhances distraction osteogenesis-mediated skeletal tissue regeneration through the recruitment of endothelial precursors

Distraction osteogenesis (DO) is a unique therapy that induces skeletal tissue regeneration without stem/progenitor cell transplantation. Although the self-regeneration property of DO provides many clinical benefits, the long treatment period required is a major drawback. A high-speed DO mouse model (H-DO), in which the distraction was done two times faster than in control DO (C-DO) mice, failed to generate new bone callus in the DO gap. We found that this was caused by the unsuccessful recruitment of bone marrow endothelial cells (BM-ECs)/endothelial progenitor cells (EPCs) into the gap. We then tested the ability of a local application of stromal cell-derived factor-1 (SDF-1), a major chemo-attractant for BM-ECs/EPCs, to accelerate the bone regeneration in H-DO. Our data showed that, in H-DO, SDF-1 induced callus formation in the gap through the recruitment of BM-ECs/EPCs, the maturation of neo-blood vessels, and increased blood flow. These results indicate that the active recruitment of endogenous BM-ECs/EPCs may provide a substantial clinical benefit for shortening the treatment period of DO.

► BMEC/EPCs recruitment was impaired in a high-speed distraction osteogenesis (H-DO). ► Application of SDF-1 promoted recruitments of BMECs/EPCs in H-DO gap. ► Application of SDF-1 promoted vessel maturation in H-DO gap. ► SDF-1-mediated neo-vascularization increased blood flow in H-DO gap. ► Application of SDF-1 restored neo bone formation in the H-DO gap.