Restoring Respiratory Motor Function with Cell Therapy after Cervical Spinal Cord Injury

More than half of all spinal cord injuries (SCI) occur at the cervical level. At this level are the components of the central nervous system mediating respiratory motor activity, including the phrenic motor neurons which innervate the diaphragm and the bulbospinal tracts that provide the inspiratory drive to these cells. Therefore, injuries at this level can result in diaphragmatic paralysis and the inability to breathe. In order to survive, mechanical ventilation is needed for these patients, severely limiting their quality of life. In this grant application we plan to utilize our newly developed cervical contusion injury model. This cervical contusion injury model is significantly improved compared to previous models of cervical injury in that accompanying it are severe respiratory motor deficits in a clinically relevant setting. Additionally, with this model we can assay potential therapeutic interventions and their effect on repairing, strengthening, and/or promoting the plasticity of pathways damaged by SCI. Among these interventions is stem cell therapy. Previous work has demonstrated the effectiveness of multipotent adult progenitor cell (MAPC) therapy in restoring locomotor and bladder function in thoracic SCI models. We now propose to determine the effectiveness of MAPC treatment in rescuing the diaphragm from paralysis. If this cell therapy is indeed therapeutically beneficial, there would be a significant and positive impact for a major portion of the SCI population.