Human ciliary neurotrophic factor-overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury

Cytotherapy. 2015 Jul;17(7):912-21. doi: 10.1016/j.jcyt.2015.03.689. Epub 2015 May 1.

Abstract

Background aims: Traumatic injury to the central nervous system (CNS) often causes motor dysfunctions. However, because of the CNS complexity and variability in the clinical presentations, efforts to repair damaged CNS tissue and restoring its functions are particularly demanding. On the other hand, recent progress in the regenerative therapy field have led to novel approaches for the treatment of traumatic CNS injury and renewed hopes to overcome the obstacles. It appears that the balance between neurite re-growth-inhibiting and neurite re-growth-inducing molecules determines the axonal re-growth fate. Neurotrophic factors can tilt this balance and indeed promote cell survival and axonal re-growth over neurodegeneration. One of the promising neurotrophic factors in this field is ciliary neurotrophic factor (CNTF).

Methods: We transfected rat bone marrow stromal cells with a mammalian expression vector-inserted human CNTF gene through the use of a non-viral method to prepare human CNTF-overexpressing stem cells under ex vivo conditions. We transplanted these modified cells to the rat model of spinal cord traumatic injury to explore functional recovery after contusion induction.

Results: Our data from immunocytochemistry and behavioral tests showed that such cells can act as a powerful potential approach to treat traumatic CNS injuries because these modified cells improved the behavioral test scores in the rat model of spinal cord injury.

Conclusions: CNTF-overexpressing bone marrow stromal cells can ameliorate spinal cord traumatic injury and can be used in the treatment of traumatic CNS injuries in the near future.

Keywords: BMSCs; CNS regeneration; CNS traumatic injury; CNTF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Bone Marrow Cells / metabolism
  • Cell Survival / drug effects
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Ciliary Neurotrophic Factor / biosynthesis
  • Ciliary Neurotrophic Factor / genetics
  • Ciliary Neurotrophic Factor / metabolism*
  • Contusions / therapy
  • Female
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism*
  • Models, Animal
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord / surgery
  • Spinal Cord Injuries / therapy*
  • Transfection

Substances

  • Ciliary Neurotrophic Factor