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

颈脊髓损伤后通过细胞疗法恢复呼吸运动功能

• 批准号: 8892369
• 负责人: Warren Joseph Alilain
• 金额: $ 19.42万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8892369
• 关键词: Adult; Americas; Animal Model; Animals; Applications Grants; Biological Assay; Bladder; Breathing; Caring; Cell Therapy; Cells; Cervical; Cervical spinal cord injury; Chest; Communities; Contralateral; Contusions; Development; Effectiveness; Emotional; Ethics; FDA approved; Facilities and Administrative Costs; Family member; Funding Opportunities; Goals; Injury; Intervention; Knowledge; Laboratories; Lateral; Limb structure; Mechanical Ventilators; Mechanical ventilation; Mediating; Medical; Modeling; Motor; Motor Activity; Motor Neurons; Natural regeneration; Neuraxis; Paralysed; Pathway interactions; Patient Care; Patients; Population; Process; Publications; Quality of life; Recovery; Respiratory Diaphragm; Respiratory Paralysis; Side; Spinal Cord; Spinal cord damage; Spinal cord injury; Spinal cord injury patients; Stem cells; Testing; Therapeutic; Therapeutic Intervention; Thoracic spinal cord structure; Time; Tissues; United States; Whole Body Plethysmography; Work; base; care burden; clinically relevant; cost; functional outcomes; improved; injured; male; mortality; motor deficit; motor recovery; neurophysiology; public health relevance; repaired; research study; respiratory; stem cell therapy; young adult

 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.

 描述（由申请人提供）：超过一半的脊髓损伤（SCI）发生在颈部。在这个水平是中枢神经系统的组分介导呼吸运动活动，包括支配隔膜的膈运动神经元和向这些细胞提供吸气驱动的球脊髓束。因此，这种程度的损伤会导致肢体瘫痪和无法呼吸。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。在这个基金申请中，我们计划利用我们新开发的颈部挫伤模型。与先前的颈部损伤模型相比，该颈部挫伤损伤模型显著改善，因为在临床相关环境中伴随其的是严重的呼吸运动缺陷。此外，通过该模型，我们可以分析潜在的治疗干预措施及其对修复，加强和/或促进SCI损伤途径的可塑性的影响。这些干预措施包括干细胞治疗。先前的工作已经证明了多能成体祖细胞（MAPC）治疗在恢复胸部SCI模型的运动和膀胱功能方面的有效性。我们现在建议确定MAPC治疗在挽救膈肌麻痹方面的有效性。如果这种细胞疗法确实在治疗上是有益的，那么对于大多数人来说， SCI人口。