Brain Advance Access published online on August 8, 2008
Brain, doi:10.1093/brain/awn173
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Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial
1National Centre for Adult Stem cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Qld 4111, Australia, 2Neurobiologie des Interactions Cellulaire et Neurophysiopathologie, CNRS UMR 6184, IFR Jean Roche, Faculté de Médecine Nord, Bd Pierre Dramard, 13916 Marseille cedex 20, France, 3Occupational Therapy Department, Ipswich Hospital, Ipswich, Qld 4305, Australia, 4Spinal Outreach Team, 5Spinal Injuries Unit, Queensland Spinal Cord Injuries Service, Princess Alexandra Hospital, Woolloongabba, Qld 4102, 6Department of Mental Health, Gold Coast Hospital, Southport, Qld 4215, 7School of Human Movement Studies & Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Qld 4059, 8Northside Spinal Research Group, Holy Spirit Northside Hospital, Chermside, Qld 4302, 9Department of Neurosurgery and 10Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Woolloongabba, Qld 4102, Australia
Correspondence to:
Dr Alan Mackay-Sim, National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Qld 4111, Australia E-mail: a.mackay-sim{at}griffith.edu.au
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.
Key Words: human; transplantation; spinal cord injury; paraplegia
Abbreviations: ASIA, American Spinal Injury Association Impairment Scale; COVS, Clinical Outcome Variables Scale; FDI, first dorsal interoseous; FIM, Functional Independence Measure; IADL, Instrumental Activities of Daily Living; MRI, Magnetic Resonance Imaging; SSEP, somatosensory evoked potentials; TMS, transcranial magnetic stimulation; ZPP, zone of partial preservation
Received April 17, 2008. Revised July 4, 2008. Accepted July 4, 2008.
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