Restoring Function After Spinal Cord Injury: Promoting Spontaneous Regeneration with Stem Cells and Activity-Based Therapies

SCI is a debilitating injury of the CNS that evolves in several stages: development, acute injury (primary and secondary injury), subchronic injury, chronic injury, and aging. Individuals with chronic SCI are known to lose motor and sensory function below the injury level over a matter of years, and they frequently experience pain, bladder and bowel dysfunction, sexual dysfunction, and autonomic dysreflexia. Several molecular and cellular therapeutic approaches are showing great promise for restoring meaningful function after SCI, however. Additionally, the development of important assessment tools, such as high-resolution advanced MRI, promises to offer superior methods for injury characterization, assessment, classification, prognostication, and treatment tailoring. Advanced structural MRI should enable us to measure the extent of SCI and to tailor treatments according to the microscopic anatomy of an injury. Such treatments might include transplantation of neuronal or oligodendrocyte progenitors derived from hES cells. ES cells are much less likely than somatic cells to be rejected by the host's immune system because of their low alloantigen expression. Also, the CNS offers the benefit of transplantation into an immunologically privileged site. Animal experiments have already shown that transplanted ES cells can remyelinate damaged axons, integrate themselves into the host's motor and sensory circuits, and induce functional improvements. Although cell transplantation alone is unlikely to be sufficient, it could be combined with new approaches to optimize spontaneous regeneration, such as ABRT therapies, including FES cycling and PBWSW therapy, which simulate the electrical stimuli that are absent below the injury level, inducing spontaneous plasticity and regeneration. Thus, a combination of treatments is likely to offer the best chance of ameliorating symptoms and restoring useful function to patients with SCI. The next decade promises great excitement in the field of regenerative medicine and probably effective treatments for optimizing spontaneous regeneration and recovery of function in chronic SCI.