Delivery of chondroitinase by canine mucosal olfactory ensheathing cells alongside rehabilitation enhances recovery after spinal cord injury

Jonathan Prager, Daisuke Ito, Darren R Carwardine, Prince Jiji, Divya M Chari, Nicolas Granger, Liang-Fong Wong*

*Corresponding author for this work

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

Abstract

Spinal cord injury (SCI) can cause chronic paralysis and incontinence and remains a major worldwide healthcare burden, with no regenerative treatment clinically available. Intraspinal transplantation of olfactory ensheathing cells (OECs) and injection of chondroitinase ABC (chABC) are both promising therapies but limited and unpredictable responses are seen, particularly in canine clinical trials. Sustained delivery of chABC presents a challenge due to its thermal instability; we hypothesised that transplantation of canine olfactory mucosal OECs genetically modified ex vivo by lentiviral transduction to express chABC (cOEC-chABC) would provide novel delivery of chABC and synergistic therapy. Rats were randomly divided into cOEC-chABC, cOEC, or vehicle transplanted groups and received transplant immediately after dorsal column crush corticospinal tract (CST) injury. Rehabilitation for forepaw reaching and blinded behavioural testing was conducted for 8 weeks. We show that cOEC-chABC transplanted animals recover greater forepaw reaching accuracy on Whishaw testing and more normal gait than cOEC transplanted or vehicle control rats. Increased CST axon sprouting cranial to the injury and serotonergic fibres caudal to the injury suggest a mechanism for recovery. We therefore demonstrate that cOECs can deliver sufficient chABC to drive modest functional improvement, and that this genetically engineered cellular and molecular approach is a feasible combination therapy for SCI.
Original languageEnglish
Article number113660
Number of pages14
JournalExperimental Neurology
Volume340
Early online date26 Feb 2021
DOIs
Publication statusPublished - 1 Jun 2021

Bibliographical note

Publisher Copyright:
© 2021

Keywords

  • Olfactory ensheathing cells
  • Chondroitinase ABC
  • Spinal cord injury
  • Genetic engineering
  • Combination therapy

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