Diaphragmatic Transplantation for Muscular Dystrophy

膈肌移植治疗肌营养不良症

• 批准号: 7140246
• 负责人: George Alexander Patterson
• 金额: $ 22.41万
• 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/7140246
• 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（由申请人提供）：杜氏肌营养不良症是人类肌营养不良症中最常见和最严重的一种，每3,500例活产男婴中就有1例受到影响。其特征在于进行性骨骼肌无力和死亡，发生在青少年晚期至20岁早期，通常是由于继发于呼吸功能障碍的呼吸并发症。专注于将细胞、基因或蛋白质递送至营养不良的肌肉组织的治疗策略已经受到限制，但是肌营养不良相关的心肌病已经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缓解呼吸衰竭。我们已经产生了初步的数据，证明在啮齿动物模型中进行肿瘤移植的可行性，我们的具体目标是：1）评估移植到遗传上相同的宿主中后的长期肿瘤存活率。我们将专门评估血流量、肌细胞存活率和纤维化。（2）评价移植血管的神经支配。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）评价移植血管的运动功能。我们将使用体内和离体制剂测试移植移植物的运动功能。在完成这些实验时，我们希望进一步确定血管移植作为治疗杜氏肌营养不良症的治疗策略的潜力，以及确定啮齿动物模型中的潜在缺陷。

项目成果

The feasibility of diaphragmatic transplantation as potential therapy for treatment of respiratory failure associated with Duchenne muscular dystrophy: acute canine model.

膈肌移植作为治疗杜氏肌营养不良相关呼吸衰竭的潜在疗法的可行性：急性犬模型。

• DOI: 10.1016/j.jtcvs.2007.12.047
• 发表时间: 2008
• 期刊: The Journal of thoracic and cardiovascular surgery
• 作者: Krupnick,AlexanderSasha;Gelman,AndrewE;Okazaki,Mikio;Lai,Jiaming;Das,Nitin;Sugimoto,Seiichiro;Tung,ThomasH;Richardson,StevenB;Patterson,GAlexander;Kreisel,Daniel
• 通讯作者: Kreisel,Daniel