Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

Abstract

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Fig. 1

Sagittal MR imaging of patients at 36 months after olfactory ensheathing cell transplants. Patients 1, 2 and 3 are shown as pairs (A and B, C and D, E and F, respectively). On the left are T₁-weighted images with gadolinium contrast. On the right are T₂-weighted images. Patient 3 has two cylindrical metal cages in the vertebral spaces, placed for treatment of the original vertebral column trauma, seen as white artifacts prominent in the T₁-weighted image.

Fig. 2

ASIA sensory scores during the period of the trial. (A) Sensory scores for light touch in the transplant recipients (closed symbols, lines) and Controls (open symbols, dotted lines). (B) Pin prick scores for pin prick in the transplant recipients (closed symbols, lines) and controls (open symbols, dotted lines).

Fig. 3

Changes in light touch and pin prick sensitivity during the period the trial. The graph shows the differences in location of sensitivity to light touch and pin prick, anteriorly and posteriorly (8 measurements per patient) at baseline (0 months) and 3 years later (36 months). The locations were measured in centimetres from the sternal notch (anteriorly) and spinous process (posteriorly).