Although many therapeutic interventions have shown promise in treating
spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following
spinal cord injury . In this study, we applied a combinatorial approach for treating
spinal cord injury involving neuroprotection and rehabilitation, exploiting
cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive
spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell
transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after
spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell
transplantation and exercise showed a better
therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell
transplantation and exercise markedly reduced fibrotic
scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell
transplantation and exercise on
spinal cord injury recovery occurred via the PI3K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell
transplantation combined with exercise training can effectively restore motor function after
spinal cord injury by activating the PI3K/AKT/mTOR pathway.