Transplantation and gene therapy: combined approaches for repair of spinal cord injury.
Motor and sensory functions are lost after spinal cord injury because neurons die or atrophy and axons fail to regenerate. Until fairly recently, it was believed that damaged neurons could not be replaced and injured axons could not regenerate, and, therefore, functions dependent on injured neurons could not be recovered. We now know that damaged neurons can be rescued by providing therapeutic factors or replaced by grafting. In addition, the adult CNS contains a population of precursor cells with a potential to generate new neural cells, whose numbers and composition can be modified by extrinsic factors. The pioneering studies of Aguayo demonstrated that CNS axons could regenerate in the right environment. Subsequent studies have revealed the identity of some of the inhibitory molecules in myelin and scar tissue, and we now have a better understanding of how the CNS environment can be modified to become more permissive to regeneration. Axons that regenerate must find an appropriate target, but it may not be essential to reestablish the precise topography for some functions to be restored. There are now new and promising strategies for delivery of therapeutic genes to protect neurons and to stimulate regeneration. The ability to engineer cells by gene therapy combines the therapeutic values of cell transplantation and gene delivery. These remarkable developments from many disciplines have generated a new level of optimism in the search for a cure for CNS injury and in particular spinal cord injury. In this review, the authors summarize recent progress in these strategies and some of the challenges that remain in elucidating the most efficacious protocols for rescuing injured neurons, encouraging regeneration of their axons, and promoting recovery of function.
Murray
M
M
Dept Neurobiology and Anatomy, MCP Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129, USA. murray@drexel.edu
Fischer
I
I
D000328:Adult; D000818:Animals; D016332:Fetal Tissue Transplantation; D015316:Genetic Therapy; D006801:Humans; D009416:Nerve Regeneration; D010525:Peripheral Nerves / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D014184:Transplantation, Homologous