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

Prager, Jon; Ito, Daisuke; Carwardine, Darren R; Jiju, Prince; Chari, Divya M; Granger, Nicolas; Wong, Liang-Fong

Authors

Jon Prager

Daisuke Ito

Darren R Carwardine

Prince Jiju

Divya M Chari

Nicolas Granger

Liang-Fong Wong



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.

Citation

Prager, J., Ito, D., Carwardine, D. R., Jiju, P., Chari, D. M., Granger, N., & Wong, L. (in press). Delivery of chondroitinase by canine mucosal olfactory ensheathing cells alongside rehabilitation enhances recovery after spinal cord injury. Experimental Neurology, https://doi.org/10.1016/j.expneurol.2021.113660

Journal Article Type Article
Acceptance Date Feb 24, 2021
Online Publication Date Mar 25, 2021
Deposit Date Mar 26, 2021
Publicly Available Date Mar 26, 2022
Journal Experimental Neurology
Print ISSN 0014-4886
Publisher Elsevier
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1016/j.expneurol.2021.113660
Public URL https://rvc-repository.worktribe.com/output/1444390

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