Transplanted iNSCs migrate through SDF-1/CXCR4 signaling to promote neural recovery in a rat model of spinal cord injury.

The ability of transplanted induced neural stem cells (iNSCs) to promote functional recovery after spinal cord injury and the mechanism by which iNSCs migrate to injured areas are poorly understood. Stromal cell-derived factor-1 (SDF-1) is a cytokine, whereas CXCR4 is its cognate receptor. The aim of this study was to determine whether SDF-1 regulates the migration of iNSCs and to explore the potential mechanism by which iNSCs promotes functional recovery. In-vitro experiments demonstrated that SDF-1 induces a concentration-dependent migration of iNSCs. Pretreatment with the CXCR4-specific antagonist AMD3100 significantly prevented the migration of iNSCs. We found that the expression of SDF-1 increased significantly in spinal cord lesions and was mainly associated with neurons and astrocytes. We also demonstrated that transplanted green fluorescent protein-labeled iNSCs were localized to regions where SDF-1 was highly expressed. In addition, iNSC-treated animals showed significantly improved functional recovery as assessed by BBB at 7 days after injection compared with controls. iNSCs also increased cell proliferation, enhanced vascularity, and reduced apoptosis. These results suggest that upregulated SDF-1 plays an important role in the migration of iNSCs to the injured region and that iNSCs are beneficial for functional recovery after spinal cord injury.