FM19G11 and Ependymal Progenitor/Stem Cell Combinatory Treatment Enhances Neuronal Preservation and Oligodendrogenesis after Severe Spinal Cord Injury

Int J Mol Sci. 2018 Jan 9;19(1):200. doi: 10.3390/ijms19010200.

Abstract

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. We have previously shown that individual therapeutic strategies, transplantation of ependymal stem/progenitor cells of the spinal cord after injury (epSPCi) or FM19G11 pharmacological treatment, induce moderate functional recovery after SCI. Here, the combination of treatments has been assayed for functional and histological analysis. Immediately after severe SCI, one million epSPCi were intramedullary injected, and the FM19G11 compound or dimethyl sulfoxide (DMSO) (as the vehicle control) was administrated via intrathecal catheterization. The combination of treatments, epSPCi and FM19G11, improves locomotor tasks compared to the control group, but did not significantly improve the Basso, Beattie, Bresnahan (BBB) scores for locomotor analysis in comparison with the individual treatments. However, the histological analysis of the spinal cord tissues, two months after SCI and treatments, demonstrated that when we treat the animals with both epSPCi and FM19G11, an improved environment for neuronal preservation was generated by reduction of the glial scar extension. The combinatorial treatment also contributes to enhancing the oligodendrocyte precursor cells by inducing the expression of Olig1 in vivo. These results suggest that a combination of therapies may be an exciting new therapeutic treatment for more efficient neuronal activity recovery after severe SCI.

Keywords: FM19G11; axon growth; ependymal progenitor stem cells; locomotion; neuronal regeneration; oligodendrogenesis; spinal cord injury.

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Benzamides / therapeutic use*
  • Cell Differentiation / drug effects
  • Ependyma / cytology
  • Female
  • Injections, Spinal
  • Locomotion / drug effects
  • Microscopy, Fluorescence
  • Neurons / cytology
  • Neurons / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Severity of Illness Index
  • Spinal Cord / pathology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation*
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • Benzamides
  • FM19G11