Spinal cord regeneration: from gene to transplants.

The past 20 years has seen the emergence of many exciting and promising experimental therapeutic strategies to promote regeneration of the injured spinal cord in laboratory animals. A greater understanding of the pathophysiologic mechanisms that contribute to the initial and secondary cord injury may facilitate the development of neuroprotective strategies that preserve axonal function and prevent apoptotic cell death, thus optimizing neurologic function. Neurotrophic factors have been used to augment the poor intrinsic regenerative capacity of central nervous system neurons, and the need for sophisticated delivery of such trophic agents has stimulated the application of gene therapy in this context. In addition to augmenting the neuronal capacity to regenerate axons, many researchers are developing strategies to overcome the inhibitory environment into which these axons must grow. Characterizing the inhibitory elements of the glial scar at the site of injury and of myelin in the distal tracts is therefore a focus of intense scientific interest. To this effect, a number of strategies have also been developed to bridge the injury site and facilitate axonal growth across the lesion with a variety of cellular substrates. These include fetal tissue transplants, stem cells, Schwann cells, and olfactory ensheathing cells. With the collaboration of basic scientists and clinicians, it is hoped that these experimental strategies coupled with a greater understanding of the neurobiology of spinal cord injury will be translatable to the clinical setting in the near future.