Repair and regeneration of lumbosacral nerve defects in rats with chitosan conduits containing bone marrow mesenchymal stem cells

Injury. 2015 Nov;46(11):2156-63. doi: 10.1016/j.injury.2015.08.035. Epub 2015 Sep 1.

Abstract

Objectives: Despite the great progress in surgical treatment of lumbosacral nerve injuries caused by high-energy trauma, functional recovery remains poor and insufficient. Bone marrow mesenchymal stem cells (BMSCs), which express neurotrophic factors and can also differentiate into nerve cells, have potential as an effective alternative therapy for lumbosacral nerve defects. The aim of the present study was to evaluate the functional recovery, nerve regeneration, motor neuron survival and apoptosis after lumbosacral nerve transection in rats receiving BMSC transplantation into the chitosan conduit.

Methods: The right L4-L6 nerve roots of rats were transected and bridged with three 1-cm-long chitosan conduits, which were further injected with the BMSCs (MSC-treated group) or culture medium (DMEM group). The nerve regeneration and motor function recovery were assessed by the sciatic functional index (SFI) and analysed electrophysiologically and morphologically.

Results: At 6 and 12 weeks after surgery, the SFI values in MSC-treated group were significantly higher than those in DMEM group (P≤0.05). The peak amplitude of CMAP (compound muscle action potential) and nerve conduction velocity in MSC-treated group were significantly higher than that in DMEM group (P≤0.01), while the latency of CMAP onset in MSC-treated group was significantly shorter than that in DMEM group (P≤0.01). The diameter of the myelinated fibres and thickness of the myelin sheath in MSC-treated group were significantly higher than those in DMEM group (P≤0.05). There was no difference in the number of motor neurons in the anterior horn of the spinal cord at 6 weeks post-operation (P>0.05), while the number of motor neurons was significantly greater in MSC-treated group than that in DMEM group at 12 weeks post-operation (P≤0.001). The number of apoptotic cells was also significantly lower (P≤0.01).

Conclusions: The results of the present study showed that BMSCs treatment improved lumbosacral nerve regeneration and motor function. In addition, our data suggested that BMSCs inhibited motor neuron apoptosis, and improved motor neuron function and survival in the anterior horn of the spinal cord.

Keywords: Bone marrow mesenchymal stem cells; Motor neurons apoptosis; Nerve regeneration; Sacral nerve.

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology
  • Chitosan / pharmacology*
  • Coated Materials, Biocompatible / pharmacology*
  • Disease Models, Animal
  • Guided Tissue Regeneration / methods
  • Mesenchymal Stem Cell Transplantation
  • Motor Activity
  • Nerve Regeneration
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / physiopathology

Substances

  • Coated Materials, Biocompatible
  • Chitosan