Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Darren Carwardine, Jonathan Prager, Jacob Neeves, Elizabeth M Muir, James Uney, Nicolas Granger, Liang-Fong Wong

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)
284 Downloads (Pure)

Abstract

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients.

Original languageEnglish
Pages (from-to)e0188967
JournalPLoS ONE
Volume12
Issue number12
DOIs
Publication statusPublished - 11 Dec 2017

Keywords

  • Animals
  • Axons
  • Chondroitin ABC Lyase
  • Chondroitin Sulfate Proteoglycans
  • Dog Diseases
  • Dogs
  • Olfactory Mucosa
  • Spinal Cord Injuries
  • Journal Article

Fingerprint Dive into the research topics of 'Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury'. Together they form a unique fingerprint.

Cite this