Transplantation of bone marrow mesenchymal stem cells pretreated with valproic acid in rats with an acute spinal cord injury

Abstract

This study aimed to investigate whether valproic acid (VPA) pretreatment enhances the therapeutic effectiveness of mesenchymal stem cells derived from bone marrow (BMSCs) transplanted into rats with an acute spinal cord injury (SCI). BMSCs were pretreated with VPA before transplantation and then intravenously injected 1 week after SCI. Before transplantation, levels of CXC chemokine receptor 4 (CXCR4) expression in BMSCs were tested using quantitative real-time PCR and Western blotting. Stromal derived factor-1 (SDF-1), the unique ligand of CXCR4, was quantified using RT-PCR and immunofluorescence. The locomotor function of rats with an SCI was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Fluorescence microscopy and hematoxylin-eosin (HE) staining were also performed to evaluate pathophysiological changes after transplantation. On day 7 after SCI, the level of SDF-1 expression peaked. CXCR4 expression increased significantly in BMSCs pretreated with VPA. After intravenous transplantation, BrdU-labeled BMSCs were noted at the spinal injury site, and this was especially true for BMSCs pretreated with VPA. More significant functional improvement was observed in rats receiving BMSCs pretreated with VPA than in other groups of rats. AMD3100 partially inhibited improvement. This study demonstrates that pretreatment with VPA before transplantation enhances the therapeutic benefits of BMSCs in terms of greater cell migration and better neurological outcomes after traumatic SCI. The mechanism of this enhancement may be related to the SDF-1/CXCR4 axis. Therefore, pretreatment of BMSCs with VPA warrants further study in relation to the treatment of traumatic SCI.