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

Carwardine, D; Prager, J; Neeves, J; Muir, E M; Uney, J; Granger, N; Wong, L F

Authors

D Carwardine

J Prager

J Neeves

E M Muir

J Uney

N Granger

L F Wong



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.

Citation

Carwardine, D., Prager, J., Neeves, J., Muir, E. M., Uney, J., Granger, N., & Wong, L. F. (2017). Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury. PLoS ONE, 12(12), https://doi.org/10.1371/journal.pone.0188967

Journal Article Type Article
Acceptance Date Nov 16, 2017
Publication Date Dec 11, 2017
Deposit Date Feb 7, 2018
Publicly Available Date Mar 28, 2024
Journal PLoS One
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 12
Issue 12
DOI https://doi.org/10.1371/journal.pone.0188967
Public URL https://rvc-repository.worktribe.com/output/1389818

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