Chondroitinase administration and pcDNA3.1-BDNF-BMSC transplantation promote motor functional recovery associated with NGF expression in spinal cord-transected rat

Spinal Cord. 2016 Dec;54(12):1088-1095. doi: 10.1038/sc.2016.55. Epub 2016 Jun 28.

Abstract

Study design: We evaluated whether combination of chondroitinase (chABC) administration and brain-derived neurotrophic factor (BDNF)-mesenchymal stem cell (MSC) transplantation could provide an optimal effect for the treatment of spinal cord injury (SCI) subjected to complete transection.

Objectives: Behavioral assessments and DBA tracing were used to evaluate the effects of combination of chABC administration and BDNF-MSC transplantation on axonal regeneration and functional improvement in SCT rats.

Setting: Sichuan, ChinaMethods:Bone mesenchymal stem cells (BMSCs) were cultured and overexpressed BDNF recombinant vector was constructed into MSCs, then transplanted into the impaired spinal cord, together with chABC administration. Finally, the cortical spinal tract regeneration was detected by DBA tracing at 4 weeks post operation, and the expression of nerve growth factor (NGF), BDNF, neurotrophic factor (NT)-3, NT-4, fibroblast growth factor (FGF-2)-2, B cell lymphoma 2 (BCL-2) assaciated X protein (BAX) and BCL-2 in the caudal cord tissues was assessed by reverse transcription-PCR.

Results: Animals received both BDNF-BMSC transplantation and chABC administration presented the best functional recovery and obvious axonal regeneration. Moreover, NGF expression was significantly higher than that in the other groups.

Conclusion: Co-treated strategy could effectively promote motor functional recovery and axonal regeneration in SCT rats associated with NGF upregulation.

MeSH terms

  • Animals
  • Bone Marrow Transplantation / methods
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cells, Cultured
  • Chondroitinases and Chondroitin Lyases / administration & dosage*
  • Disease Models, Animal
  • Female
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism
  • Nerve Growth Factor / metabolism*
  • Nerve Regeneration / physiology
  • Neuroanatomical Tract-Tracing Techniques
  • Neuroprotective Agents / administration & dosage*
  • Rats
  • Recovery of Function / physiology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Transfection

Substances

  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Nerve Growth Factor
  • Chondroitinases and Chondroitin Lyases