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

 描述(申请人提供)：超过一半的脊髓损伤(SCI)发生在颈椎水平。在这个水平是中枢神经系统调节呼吸运动活动的组成部分，包括支配隔膜的膈运动神经元和为这些细胞提供吸气驱动的球脊髓束。因此，这种程度的损伤可能会导致横隔膜瘫痪和无法呼吸。为了生存， 这些患者需要机械通气，严重限制了他们的生活质量。在拨款申请中，我们计划使用我们新开发的颈部挫伤模型。这种颈椎挫伤模型与以前的颈椎损伤模型相比有显著的改进，因为它伴随着临床相关环境中严重的呼吸运动障碍。此外，利用这个模型，我们可以分析潜在的治疗干预措施及其在修复、加强和/或促进脊髓损伤损伤的通路可塑性方面的效果。在这些干预中，干细胞疗法就是其中之一。以前的工作已经证明了多潜能成体祖细胞(MAPC)治疗在恢复胸部脊髓损伤模型中的运动和膀胱功能方面的有效性。我们现在建议确定MAPC治疗在将横隔膜从瘫痪中拯救出来的有效性。如果这种细胞疗法确实在治疗上是有益的，那么将对很大一部分 SCI人群。

 DESCRIPTION (provided by applicant): 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 a 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 ths 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 relevnt 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.