Neurorehabilitation with neural transplantation

Cell replacement therapy has been tested clinically in Parkinson's disease (PD) and Huntington's disease (HD), epilepsy, spinal cord injury, and stroke. The clinical outcomes have been variable, perhaps partly because of the differing levels of preclinical, basic experimental evidence that was available prior to the trials. The most promising results have been seen in PD trials, with encouraging ones in HD. A common feature of most trials is that they have concentrated on the biological and technical aspects of transplantation without presupposing that the outcomes might be influenced by events after the surgery. The growing evidence of plasticity demonstrated by the brain and grafts in response to environmental and training stimuli such as rehabilitation interventions has been mostly neglected throughout the clinical application of cell therapy. This review suggests that a different approach may be required to maximize recovery: postoperative experiences, including rehabilitation with explicit behavioral retraining, could have marked direct as well as positive secondary effects on the integration and function of grafted cells in the host neural system. The knowledge gained about brain plasticity following brain damage needs to be linked with what we know about promoting intrinsic recovery processes and how this can boost neurobiological and surgical strategies for repair at the clinical level. With proof of principle now established, a rich area for innovative research with profound therapeutic application is open for investigation.