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What Matters in Cellular Transplantation for Spinal Cord Injury: The Cells, the Rehabilitation, or the Best Mix?

Lima and colleagues recently reported the results on 20 patients with chronic sensorimotor or motor complete spinal cord injury (SCI) after they performed partial scar removal and implantation of a mix of neural stem and olfactory ensheathing cells (OECs) derived from mucosal autografts1. In this uncontrolled but well-planned phase 2 study2,3, the subjects also received, immediately prior to the cellular intervention, a median of 400 hours of lower extremity step training either over ground or with a Lokomat electromechanical device. These therapies were restarted and continued for at least a year after surgery. Thus, an intensive, task-related rehabilitation program for walking was built into the trial to try to produce further recovery4. Preoperatively, they sought a stable baseline, reducing the likelihood that latent function might improve from physical therapies alone. Then, they hoped the therapies would maximize contributions from the cells. Remarkably, new signs of motor control were found from 1 to 3 years later. For example, 75% of subjects developed electromyographic activity below their lesions, and the American Spinal Injury Association Impairment Scale of motor strength improved by 4 to 8 points in 5 subjects and by 14 to 20 in another 4. The Walking Index for SCI scores of assisted walking improved in relation to greater motor control5,6. The increase in voluntary movement was found, however, only in the patients at the 2 sites that provided assisted overground stance and step training but not at the site that offered only the robotic stepper. The implication, then, is that the cells had a biological effect that depended on the type of practice. In this case, the 2 rehabilitation strategies differed in that overground training may enable greater incorporation of feedback and more trial and error to successfully approximate components of movements, compared with the rather inflexible kinematics with training on the robotic device. This potential confounder for the utility of electromechanical assists has been noted in randomized clinical trials of upper and lower extremity devices, in which the robotics were no better, or worse than, hands-on therapy of the same intensity and duration7-11.