REPAIR OF SPINAL ROOT LESIONS BY TRANSPLANTATION OF OLFACTORY ENSHEATHING CELLS CULTURED FROM THE ADULT OLFACTORY SYSTEM

Injuries to the brain and spinal cord may lead to irreparable disabilities. In rat experiments we have found a type of cell which can be cultured from a stem cell present in adult tissues. When transplanted into an injury site, these cells induce regrowth of the severed nerve fibres and restore function. We seek to provide the information needed to translate this to a first clinical trial in a specific type of human injury which is usually the result of traffic accidents, and where nerves are torn out of the spinal cord. Such injuries lead to paralysis, loss of sensation, loss of bowel and bladder control, sexual functions, and frequently intractable pain.

There is already, in our hospital, a routine procedure for re-implanting the severed nerves. This leads to some recovery of the larger muscles, but the hand remains paralysed and the leg cannot be used in walking. No sensation is restored, and there is a limited reduction of pain. In initial experiments in a rat model the transplanted cells bring back the sensation needed for hand movements and increase the outgrowth of nerve fibres from the spinal cord. This proposal is to determine:

(a) the range of sensations which can be restored by these transplants and

(b) the extent to which leg movements can be restored. This will provide the evidence needed to translate this experimental data to a clinical trial.

Reparative cells will be cultured from samples of stem cell containing tissue from the adult olfactory system. Dorsal (sensory) and ventral (motor) spinal roots will be detached from the spinal cord. We will re-appose these roots to the spinal cord. Using a specific endogenous matrix system which we have devised we will determine the effect of including these cells into the site of re-apposition. The results will be analysed in terms of the ability of severed nerve fibres to cross the transplants and the restoration of pain, touch and temperature sensation, and the degree of return of control over muscle function. This will provide an animal model for future translation to clinical application.

Brachial plexus and spinal cord injuries are sudden, devastating injuries that occur most commonly in young people at the prime of their lives. At present there is no direct treatment that is available to help these individuals return to independence, although good rehabilitation allows patients to adapt to their new situation and sometimes there can be a small degree of spontaneous recovery. At the National Hospital for Neurology and Neurosurgery the operation of brachial plexus repair, by re-implanting nerve roots into the spinal cord, is being performed as a routine NHS operation. Although there are improvements in arm function and pain, the benefits can sometimes be limited, and therefore we need a better way of reconnecting the severed pathways to improve function.

In the field of experimental spinal cord repair, many different strategies are being tested in the laboratory; olfactory ensheathing cell transplants are one of the most promising. They have the potential to fulfil many of the experimental criteria for spinal cord and root repair, by bridging gaps, providing growth factors, guiding nerve fibres and encouraging plasticity. They have considerable impact in this field because they effectively combine several regenerative strategies into one, and may contribute a very elegant solution to a complex problem.

In the clinic, if OECs can improve the outcome after brachial plexus and spinal cord injury, then this has considerable impact on the physical and psychological well-being of the patient. In addition, functional improvements should result in lower economic costs for the NHS and improved independence for patients in line with the Department of Health's National Service Framework for long-term (neurological) conditions. The potential to improve nerve injuries with OEC transplants may be applied in the future to other conditions such as optic nerve damage, glaucoma, acoustic nerve injury, or indeed any CNS injury.