Delivery of chondroitinase by canine mucosal olfactory ensheathing cells alongside rehabilitation enhances recovery after spinal cord injury
| Autor: | Darren Carwardine, Jon Prager, Daisuke Ito, Prince Jiju, Liang-Fong Wong, Nicolas Granger, Divya M. Chari |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Chondroitinase ABC Spinal cord injury Serotonergic 03 medical and health sciences 0302 clinical medicine Dogs Developmental Neuroscience RC925 Olfactory Mucosa Paralysis Medicine Animals Combination therapy Axon Rats Wistar Cells Cultured Spinal Cord Injuries business.industry Recovery of Function medicine.disease Chondroitinases and Chondroitin Lyases Rats Transplantation 030104 developmental biology medicine.anatomical_structure Neurology Anesthesia Olfactory ensheathing cells Genetic engineering Corticospinal tract Olfactory ensheathing glia medicine.symptom business 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | Prager, J, Ito, D, Carwardine, D R, Jiji, P, Chari, D M, Granger, N & Wong, L-F 2021, ' Delivery of chondroitinase by canine mucosal olfactory ensheathing cells alongside rehabilitation enhances recovery after spinal cord injury ', Experimental Neurology, vol. 340, 113660 . https://doi.org/10.1016/j.expneurol.2021.113660 |
| ISSN: | 1090-2430 0014-4886 |
| DOI: | 10.1016/j.expneurol.2021.113660 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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