Core 1: Muscular Dystrophy Cell and Serum Banking Core

核心 1：肌营养不良症细胞和血清库核心

• 批准号: 10017016
• 负责人: Kim Lewis McBride
• 金额: $ 22.51万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-14 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017016
• 关键词: Address; Antibodies; Applications Grants; Biological Models; Biopsy; Cell Culture Techniques; Cell Line; Cells; Clinic; Coculture Techniques; Communities; Congenital Heart Defects; Dermal; Development; Doxycycline; Duchenne muscular dystrophy; Exons; Expression Profiling; Facioscapulohumeral Muscular Dystrophy; Fibroblasts; Future; Gene Transfer; Gene therapy trial; Genetic study; Goals; Human; Immunity; Institutional Review Boards; Laboratories; Lentivirus Vector; Limb-Girdle Muscular Dystrophies; Merosin-Deficient Congenital Muscular Dystrophy 1A; Methods; Mission; Muscle; Muscle Cells; Muscle Fibers; Muscular Dystrophies; Mutation; Ohio; Pathogenesis; Pathogenicity; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Plasma; Prevalence; Process; Production; Protocols documentation; Reagent; Regulator Genes; Research; Research Institute; Research Personnel; Research Subjects; Resource Sharing; Resources; Sampling; Serum; Services; Skeletal Muscle; Skin; Source; System; Techniques; Testing; Time; Tissues; Translational Research; Translations; Variant; Viral Vector; autism spectrum disorder; biobank; cell immortalization; design; effective therapy; gene therapy; human disease; human subject; human tissue; improved; mRNA Expression; novel; premature; programs; research study; therapeutic development; transdifferentiation; vector

Muscular Dystrophy Cell Line and Serum Banking Core ABSTRACT The over-arching theme for this P50 CORT grant application is to accelerate the translation of novel genetic therapies from the bench into the clinic. A significant bottleneck in studying pathogenic variants or their correction in the various muscular dystrophies is the limiting factor of a muscle cell model system using patient derived myocytes. The proliferative capacity of muscle cells from muscular dystrophy patients is limited, and the process to obtain cells (muscle biopsy) is invasive. A technique using lentiviral vectors for both hTERT and MyoD delivery to the fibroblasts to create myogenic fibroblasts (hereafter called FibroMyoD) will overcome this bottleneck. The overall objective of the Muscular Dystrophy Cell Line and Serum Banking Core (MD-CLSB Core) will be preparing and banking human primary and immortalized cell lines that will support each of the CORT Projects, as well as for serum and plasma banking for exploratory and collaborative projects. The overall objective will be addressed in three specific aims. Aim 1 will create a unique cell line resource from muscular dystrophy subjects by banking dermal fibroblasts, obtained by skin biopsy, and creating FibroMyoD cell lines. Aim 2 will establish a serum biobank resource, through banking of samples obtained from clinic patients and research subjects, and make these samples available to CORT and external affiliated investigators for hypothesis-driven and discovery research. Finally, in Aim 3, we will develop an improved transdifferentiation protocol to generate mature myofibers from the FibroMyoD lines that more closely mimic mature myofibers. This MD-CLSB Core will leverage the existing expertise of the Nationwide Children's Hospital (NCH) Research Institute Cell Line Core, directed by Kim L. McBride, MD. This institutionally-supported shared resource has been creating and banking cell lines for nearly 10 years, and for the past three years has created primary fibroblast cell lines for the laboratory of the proposed CORT director, Dr. Kevin Flanigan. The current proposal will involve a greatly increased demand on the existing NCH Cell Line Core, and establishment of the CORT Core will provide the additional resources needed to serve as a resource to both the NCH and the broader muscle research community. The cell lines generated and serum samples stored will be a valuable resource for the projects of the proposed CORT, and the broader muscular dystrophy research community, in direct alignment with the P50 CORT mission.

肌肉营养不良细胞系和血清银行核心 抽象的 该P50 Cort Grant应用程序的总体主题是加速新型遗传的翻译 从长凳上进行疗法到诊所。研究致病变体或其 各种肌肉营养不良的校正是使用肌肉细胞模型系统的限制因素 患者衍生出心肌细胞。肌肉营养不良患者的肌肉细胞的增殖能力是 有限，获得细胞（肌肉活检）的过程是侵入性的。使用慢病毒向量的技术 HTERT和MYOD都交付到成纤维细胞以创建成肌成纤维细胞（以下称为 纤维瘤）将克服这种瓶颈。肌肉营养不良细胞系的总体目标和 血清银行核心（MD-CLSB核心）将准备和银行人类主要和永生的细胞 将支持每个Cort项目的线路，以及血清和血浆银行业务以进行探索 和协作项目。总体目标将以三个具体目标解决。 AIM 1将创建一个 由皮肤获得的肌肉营养不良受试者来自肌肉营养不良受试者的独特细胞系资源，由皮肤获得 活检，并创建纤维肌棒细胞系。 AIM 2将通过银行建立血清生物库资源 从诊所患者和研究对象获得的样本，并将这些样本可用于Cort和 假设驱动和发现研究的外部关联研究者。最后，在AIM 3中，我们将发展 改进的转分化方案，以产生来自纤维瘤线的成熟肌纤维，更多 紧密模仿成熟的肌纤维。这个MD-CLSB核心将利用全国范围的现有专业知识 儿童医院（NCH）研究所细胞系核心，由医学博士Kim L. McBride执导。这 机构支持的共享资源已经创建和银行单元线已有近10年了，为 在过去的三年中 凯文·弗拉尼根（Kevin Flanigan）博士。当前的建议将涉及对现有NCH单元线的需求大大增加 核心和Cort Core的建立将提供作为资源所需的额外资源 NCH和更广泛的肌肉研究界。细胞系生成和血清样品 存储将是提议的Cort项目和更广泛的肌肉的宝贵资源 营养不良研究社区与P50 Cort任务直接保持一致。