title: 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.
authors.affiliation: National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Qld, Australia. a.mackay-sim@griffith.edu.au
authors.forename: A
authors.initials: A
authors.lastname: Mackay-Sim
authors.forename: F
authors.initials: F
authors.lastname: Féron
authors.forename: J
authors.initials: J
authors.lastname: Cochrane
authors.forename: L
authors.initials: L
authors.lastname: Bassingthwaighte
authors.forename: C
authors.initials: C
authors.lastname: Bayliss
authors.forename: W
authors.initials: W
authors.lastname: Davies
authors.forename: P
authors.initials: P
authors.lastname: Fronek
authors.forename: C
authors.initials: C
authors.lastname: Gray
authors.forename: G
authors.initials: G
authors.lastname: Kerr
authors.forename: P
authors.initials: P
authors.lastname: Licina
authors.forename: A
authors.initials: A
authors.lastname: Nowitzke
authors.forename: C
authors.initials: C
authors.lastname: Perry
authors.forename: P A S
authors.initials: PA
authors.lastname: Silburn
authors.forename: S
authors.initials: S
authors.lastname: Urquhart
authors.forename: T
authors.initials: T
authors.lastname: Geraghty
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration; D009831:Olfactory Mucosa / Q000166:cytology / Q000637:transplantation*; D010147:Pain Measurement; D010264:Paraplegia / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000601:surgery*; D020127:Recovery of Function; D012677:Sensation; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000601:surgery*; D013904:Thoracic Vertebrae; D016896:Treatment Outcome