Abstract

Canine spinal cord injury (SCI) occurs spontaneously, and ~2 cases per day present to large veterinary hospitals in the United Kingdom. This injury provides an excellent model of human SCI with clinical heterogeneity that is lacking in rodent models, mixed contusive-compressive lesions of comparable size to humans and similar tools to measure clinical ‘real-life’ outcomes after injury. There is currently no treatment for severely affected dogs and they therefore present a unique opportunity for in vivo clinical research. By enabling screening for treatments with a clinically detectable effect, this model can help bridge the gap in translating therapies from the lab to humans. Using this canine model, we have: (i) performed autologous spinal transplant of canine olfactory ensheathing cells (cOECs) in clinical cases within a veterinary hospital, a technique known to improve locomotion after SCI in dogs and so far in phase 1/2 trials in humans; (ii) obtained cOECs by minimally invasive endoscopic nasal mucosal biopsy and cultured these in 3D through collagen hydrogels, a leading biomaterial for protected cell delivery in SCI ; (iii) obtained novel data on the in vivo elasticity of the spinal cord using ultrasound elastography intraoperatively, which will provide a target for matched biomaterial stiffness; (iv) developed a lentiviral vector for transduction of cOECs with the chondroitinase ABC gene. Chondroitinase ABC breaks down the glial scar formed following SCI and has been demonstrated to improve functional outcomes in experimental rodent and feline models of SCI ; and (v) developed neuroprosthesis for bladder control and treatment of neurogenic urinary incontinence. This work could be readily progressed to dogs with transduced cOECs expressing ChABC transplanted within hydrogel, potentially in combination with neuroprosthesis enabling training and rehabilitation. The clinical canine model of SCI is an example of the opportunities available for using veterinary cases in translational research.