Electrophysiological evidence that olfactory cell transplants improve function after spinal cord injury

Abstract

Transplants of cells obtained from the olfactory system are a potential treatment for spinal cord injury and a number of clinical trials are in progress. However, the extent to which transplants improve recovery of function remains unclear and there are contradictory reports on the extent to which they support axonal regeneration. Here, we have used anatomical and electrophysiological techniques to investigate the repair promoted by olfactory cell transplants after a dorsal column lesion. Since the use of olfactory cells of varying type and origin may contribute to the differing outcomes of previous studies, regeneration of dorsal column axons was compared following transplants of pure olfactory ensheathing cells from neonatal animals and mixed olfactory cells from both neonatal and adult rats. Two to three months after lesioning, numerous regenerating fibres could be seen in each type of transplant. However, tracing of ascending dorsal column fibres showed that few regenerated beyond the lesion, even when transplanted with mixed olfactory cells from the adult olfactory bulb which have previously been reported to support regeneration which bridges a lesion. Despite the absence of axonal regeneration across the injury site, olfactory cell transplants led to improved spinal cord function in sensory pathways investigated electrophysiologically. When cord dorsum potentials (CDPs), evoked by electrical stimulation of the L4/L5 dorsal roots, were recorded from the spinal cord above and below a lesion at the lumbar 3/4 level, CDPs recorded from transplanted animals were significantly larger than those recorded from lesioned controls. In addition, sensory evoked potentials recorded over the sensorimotor cortex were larger and detectable over a more extensive area in transplanted animals. These results provide direct evidence that transplants of olfactory cells preserve the function of circuitry in the region of the lesion site and of ascending pathways originating near the injury. These actions, rather than axonal regeneration, may help ameliorate the effects of spinal cord injury.