Enhanced neuroregenerative effects by scaffold for the treatment of a rat spinal cord injury with Wnt3a-secreting fibroblasts

Acta Neurochir (Wien). 2013 May;155(5):809-16. doi: 10.1007/s00701-013-1663-7. Epub 2013 Mar 3.

Abstract

Background: Wnt proteins are bifunctional axon guidance molecules, several of which appear to mediate guidance of corticospinal tract axons along the spinal cord. Here, we studied increasing effect on regeneration by Wnt-containing alginate scaffolds on spinal cord injury (SCI).

Methods: A total of 32 rats were injured at the T7-8 level with an NYU impactor. According to transplantation materials, rats were classified into four groups: a Wnt3a-secreting fibroblast transplantation group (Wnt group, n = 8), a Wnt3a-secreting fibroblast with alginate transplantation group (Wnt + alginate group, n = 8), an alginate transplantation group (alginate group, n = 8), and a contusion-only group (sham group, n = 8). Behavioral tests were performed on the first, second, and third days after injury, and then weekly for 8 weeks. Five of the eight rats from each group were selected for manganese-enhanced magnetic resonance imaging (ME-MRI). Two rats from each group were examined for GAP43 and MAP2 expression using monoclonal and polyclonal primary antibodies, respectively.

Results: Seven weeks after transplantation (8 weeks after SCI), Wnt + alginate group rats achieved an average Basso-Beattie-Bresnahan locomotor score of 19.0, which was significantly higher than that of other groups. ME-MRI at 8 weeks after SCI revealed significantly higher relative signal intensities in the Wnt + alginate group. Gap43 and Map2 immunostaining, showed strong positive in the Wnt + alginate group.

Conclusion: The Wnt + alginate complex exerted significantly enhanced recovery in a rat SCI model compared to alginate or Wnt3a alone. These results suggest that alginate scaffolds facilitate the regeneration of axon working with Wnt3a protein that promotes regeneration of the injured spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates
  • Animals
  • Axons / pathology
  • Disease Models, Animal
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / transplantation
  • Glucuronic Acid
  • Hexuronic Acids
  • Nerve Regeneration*
  • Rats
  • Rats, Wistar
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Treatment Outcome
  • Wnt3A Protein / metabolism*

Substances

  • Alginates
  • Hexuronic Acids
  • Wnt3A Protein
  • Glucuronic Acid