The functional effects of olfactory ensheathing cell transplantation on severe clinical spinal cord injury in dogs

This project will determine whether transplanting a special type of cell improves the outcome after severe spinal cord injury (SCI) in dogs. These dogs will be veterinary patients – domestic dogs that have incurred SCI during their life as pets. Veterinary treatment of spinal cord injury (SCI) in dogs is very similar to that in humans, and similarly limited in its ability to restore lost function.

We will transplant olfactory ensheathing cells (OEC), which are found in the parts of the nervous system that deal with olfaction (smell) and allow re-growth of previously damaged nerve fibres in the spinal cord, which normally does not happen. Their beneficial effect on recovery after experimental SCI in laboratory rats has been shown on numerous occasions but we now need to determine whether the effect in lab animals can be duplicated in real-life clinical injuries.

This study in canine patients provides a missing link between experimental results in lab animals and the human clinic. The results of this project will be critically important for determining whether to go ahead with a human trial and will also provide important information for understanding how the spinal cord responds to injury.

Although intraspinal transplantation of olfactory ensheathing cells (OECs) has been associated with a beneficial effect on functional outcome after experimental spinal cord lesions in laboratory rodents there are several reasons why this effect cannot be taken for granted if it were to be translated into human spinal cord injury (SCI). This is partly because clinical lesions differ greatly in size and pathogenesis from experimental lesions in rodents. More importantly, clinical categories of SCI, no matter how they are defined, are heterogenous ? containing lesions of varying histological type and severity, meaning that small treatment effects may become lost in the ?noise? of clinical variability.

SCI is a common clinical problem in dogs and there is a cohort of severely affected individuals in which conventional treatment fails to restore adequate function ? forming a suitable population for assaying the value of putative therapies for clinical SCI in humans. We have previously established that autologous OECs can be harvested, multiplied in vitro and transplanted into such affected dogs without evidence of detrimental effects. In this current project we will compare the efficacy in restoring lost function between: a) intraspinal OEC transplants, and b) intraspinal injection of cell transport medium alone. Treatments will be randomised and the outcome measures will be determined by a masked observer. We will focus on: i) analysis of data produced by digitising the gait of dogs as they walk on a treadmill, permitting quantification of the inter-relationship between movement cycles of different limb pairs - and many other parameters, and ii) measurements of the effects on bladder filling and detrusor ? sphincter mechanism coordination using cystometry.

The results of this study will have profound implications for future clinical trials on OEC transplantation in humans, its potential as a clinical treatment modality and also provide greater understanding of the response capabilities of the injured spinal cord. In the long term, this extension of the ?dog model? of human SCI will provide a highly clinically relevant means of testing future laboratory-derived putative therapies for SCI prior to human clinical trials.