Improvement of Spinal Cord Injury (SCI) via Epothilone B (Epo B) Incorporated with Bone Marrow Mesenchymal Stem Cells (BMSC) by Down-Regulate the High Mobility Group BOX-1

Abstract

Spinal cord injury (SCI) is one of serious central nervous system injuries. There is no still effective treatment and the prognosis remains poor. Bone marrow mesenchymal stem cells (BMSCs) and Epo B are proven to promote tissue repair and regeneration. This study analyzed the potential impact of BMSCs and Epo on SCI to provide new ideas for the treatment. After establishment of SCI model, mice were randomly administered with BMSCs and/or Epo B to assess their therapeutic effects through behavioral analysis, immunohistochemistry, and Western blot. In addition, the number of host neuron and wound healing was assessed. Combined treatment of Epo B and BMSCs significantly improved the survival of neurons, increased axon growth, and promoted motor recovery following spinal cord injury. Single treatment of BMSCs or Epo B rarely improved mice’s behavior. Only combination with BMSCs and Epo B enhanced axonal extension, possibly due to the reduction of inflammation by BMSCs. In addition, we found that surviving neurons in the spinal canal are essential for the functional recovery. Collectively, the combination of BMSCs and Epo B has a neuroprotective effect on CI in rats, and achieves a promising recovery effect of motor function probably due to down-regulation of HMGB1. These findings may lay a foundation for the development of targeted therapy.