Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury.

OBJECTIVE:Numerous studies in animals have shown the unique property of olfactory ensheathing cells tostimulate regeneration of lesioned axons in the spinal cord. In a Phase I clinical trial, weassessed the safety and feasibility of transplantation of autologous mucosal olfactoryensheathing cells and olfactory nerve fibroblasts in patients with complete spinal cord injury.METHODS:Six patients with chronic thoracic paraplegia (American Spinal Injury Association class AASIA A) were enrolled for the study. Three patients were operated and three served as acontrol group. The trial protocol consisted of pre- and postoperative neuro-rehabilitation,olfactory mucosal biopsy, culture of olfactory ensheathing cells, and intraspinal cell grafting.Patient's clinical state was evaluated by clinical, neurophysiological and radiological tests.RESULTS:There were no adverse findings related to olfactory mucosa biopsy or transplantation of olfactory ensheathing cells at one year after surgery. There was no evidence of neurologicaldeterioration, neuropathic pain, neuroinfection or tumorigenesis. In one cell-grafted patient an asymptomatic syringomyelia was observed. Neurological improvement was observed only intransplant recipients. The first 2 operated patients improved from ASIA A to ASIA C andASIA B. Diffusion tensor imaging showed restitution of continuity of some white mattertracts throughout the focus of spinal cord injury in these patients. The third operated patientalthough remained ASIA A, showed improved motor and sensory function of the first spinalcords segments below the level of injury. Neurophysiological examinations showedimprovement in spinal cord transmission and activity of lower extremity muscles in surgicallytreated patients but not in patients receiving only neuro-rehabilitation.CONCLUSIONS:Observations at 1 year indicate that the obtaining, culture and intraspinal transplantation ofautologous olfactory ensheathing cells was safe and feasible. The significance of theneurological improvement in the transplant recipients and the extent to which the celltransplants contributed to it will require larger numbers of patients.