Diaphragmatic Transplantation for Muscular Dystrophy

膈肌移植治疗肌营养不良症

• 批准号: 6957080
• 负责人: George Alexander Patterson
• 金额: $ 19.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6957080
• 关键词: diaphragm; fibrosis; histology; immunocytochemistry; ischemia; laboratory rat; microsurgery; muscle cells; muscular dystrophy; respiratory circulation; respiratory transplantation; technology /technique development; terminal nick end labeling

DESCRIPTION (provided by applicant): Duchenne Muscular Dystrophy is the most common and severe of the human muscular dystrophies, affecting 1 in 3,500 live male births. It is characterized by progressive skeletal muscle weakness and death occurring in late teens to early 20's, usually from respiratory complications secondary to diaphragmatic dysfunction. Therapeutic stretegies that focus on delivering cells, genes, or proteins to the dystrophic musculature have been limited but muscular dystrophy related cardiomyopathy has been successfully treated by cardiac transplantation. Our broad objective is to translate the success of solid organ transplantation toward the palliation of respiratory failure by transplanting the main muscle of respiration. We have generated preliminary data demonstrating the feasibility of diaphragmatic transplantation in a rodent model and our specific aims are: 1)To evaluate long-term diaphragmatic survival after transplantation into genetically identical host. We will specifically evaluate blood flow, myocyte survival, and fibrosis. 2)To evaluate innervation of the diaphragmatic graft. We will specifically focus on histologic and functional evidence of reinnervation in several experimental conditions. 3)To evaluate the motor function of the diaphragmatic graft. We will test the motor function of the transplanted graft using both in vivo and ex vivo preparations. At the completion of these experiments we hope to further define the potential of diaphragmatic transplantation as a therapeutic strategy for the treatment of Duchenne Muscular Dystrophy as well as to identify potential pitfalls in a rodent model.

描述(申请人提供)：杜氏肌营养不良症是人类肌肉营养不良中最常见和最严重的一种，影响每3,500名活男婴中的1名。其特点是进行性的骨骼肌无力和死亡，发生在十几岁末到二十岁出头的S，通常是由于继发于横隔肌功能障碍的呼吸道并发症。专注于将细胞、基因或蛋白质输送到营养不良的肌肉系统的治疗方法一直受到限制，但与肌营养不良相关的心肌病已通过心脏移植成功地治疗。我们的广泛目标是通过移植呼吸的主要肌肉，将实体器官移植的成功转化为呼吸衰竭的缓解。我们已经产生了初步的数据，证明了在啮齿动物模型中进行横隔膜移植的可行性，我们的具体目标是：1)评估在基因相同的宿主中移植后横隔膜的长期存活率。我们将专门评估血流量、心肌细胞存活率和纤维化。2)评价膈神经移植物的神经支配情况。我们将特别关注在几种实验条件下神经再支配的组织学和功能证据。3)评价移植物的运动功能。我们将使用体内和体外的准备材料来测试移植的移植物的运动功能。在这些实验完成后，我们希望进一步确定横隔膜移植作为治疗Duchenne肌营养不良症的治疗策略的潜力，并在啮齿动物模型中识别潜在的陷阱。