SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model

Abstract

Background: Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to migrate to injured spinal cords and promote functional recovery when systemically transplanted into the traumatized spinal cord. However, the the mechanisms underlying their migration to spinal cords are not yet fully understoodMethods: In this study, we systemically transplanted GFP- and luciferase-expressing MSCs into the rat models of spinal cord injury and examined the role of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis in regulating the migration of transplanted MSCs to spinal cords.Results: After intravenous injection, MSCs migrated to the injured spinal cord where the expression of SDF-1 was increased. Spinal cord recruitment of MSCs was blocked by pre-incubation with an inhibitor of CXCR4. Their presence correlated with morphological and functional recovery. In vitro, SDF-1 or cerebrospinal fluid (CSF) collected from SCI rats promoted a dose-dependent migration of MSCs, which was blocked by an inhibitor of CXCR4 or an SDF-1 antibody.Conclusions: The study suggests that SDF-1/CXCR4 interactions recruit exogenous MSCs to injured spinal cord tissue and may enhance neural regeneration. Modulation of homing capacity may be instrumental in harnessing the therapeutic potential of MSCs.