Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (5): 1067-1075.doi: 10.4103/1673-5374.355762

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Bone marrow mesenchymal stem cells and exercise restore motor function following spinal cord injury by activating PI3K/AKT/mTOR pathway

Xin Sun1, 2, Li-Yi Huang1, 2, Hong-Xia Pan1, 2, Li-Juan Li1, 2, Lu Wang1, 2, Gai-Qin Pei1, 2, Yang Wang1, 2, Qing Zhang1, 2, Hong-Xin Cheng1, 2, Cheng-Qi He1, 2, Quan Wei1, 2, *   

  1. 1Rehabilitation Medical Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;  2Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, Sichuan Province, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Quan Wei, PhD, weiquan@scu.edu.cn.
  • Supported by:
    This work was supported by the National Key R&D Program of China, No.2020YFC2008502 (to QW) and the National Natural Science Foundation of China, No. 82172534 (to QW).

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Abstract: 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. 

Key words: axon growth, bone marrow mesenchymal stem cell, exercise training, mTOR, neuroprotection, neurotrophin, remyelination, scar formation, spinal cord injury, synaptic plasticity