UAB CFRC Core A: Cell Model and Evaluation Core

UAB CFRC 核心 A：单元模型和评估核心

• 批准号: 10673355
• 负责人: George Martin Solomon
• 金额: $ 30.8万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673355
• 关键词: Adopted; Animal Model; Animals; Area; Award; Biological Assay; Biological Models; Biology; Biopsy; Bronchi; Cell Culture System; Cell Culture Techniques; Cell model; Cells; Clinical; Clinical Trials; Collaborations; Complement; Complex; Cost Savings; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Development; Dyes; Epithelial Cells; Epithelium; Equipment; Evaluation; Excision; Fostering; Frequencies; Functional Imaging; Functional disorder; Funding; Gastrointestinal tract structure; Genetic; Health Insurance Portability and Accountability Act; Heterozygote; Human; Human Resources; Hydration status; Image; In Situ; In Vitro; Individual; Institutional Review Boards; Investigation; Ion Transport; Ions; Laboratories; Laboratory Research; Lung; Lung Transplantation; Measurement; Measures; Messenger RNA; Methodology; Methods; Modeling; Morbidity - disease rate; Mucociliary Clearance; Mucous body substance; Nose; Operative Surgical Procedures; Optical Coherence Tomography; Organ; Organoids; Pathogenesis; Pathway interactions; Permeability; Phenotype; Procedures; Process; Productivity; Property; Proteins; Publications; Pulmonary Cystic Fibrosis; Reagent; Rectum; Reproducibility; Research; Research Design; Research Personnel; Research Support; Resolution; Resources; Rights; Safety; Sampling; Science; Scientist; Sinus; Source; Standardization; Surface; Swelling; System; Techniques; Technology; Testing; Thick; Tissues; Trachea; Training; Translating; Translations; United States National Institutes of Health; Validation; Viscosity; Western Blotting; Work; airway epithelium; airway inflammation; airway surface liquid; anatomic imaging; body system; cystic fibrosis patients; digital; drug discovery; gene therapy; human subject; human tissue; improved; in vivo; innovation; insight; material transfer agreement; mortality; novel; novel therapeutics; protein expression; quality assurance; real-time images; rectal; repair strategy; repaired; repository; response; sample fixation; standard measure

PROJECT SUMMARY / ABSTRACT: P30 CORE A Well-differentiated human airway epithelial cells, model systems, and the assays that can be used with them are an instrumental model for understanding epithelial biology and are highly predictive of in vivo results in clinical trials. Primary cells can be used with methodologies that translate readily to assays of airway and epithelilal function in vivo, including measures of CFTR activity or other ion transporters, airway surface liquid depth and mucus hydration, mucus viscosity and transport. epithelial cell models further provide an excellent model for examining the biology of airway epithelial inflammation, which is key to the pathogenesis of cystic fibrosis (CF) lung disease. The purpose of Core A is to support the research of numerous P30 investigators that involves cell culture systems and to assist with established and innovative assays available to characterize cellular responses. Core A carries out three main functions as outlined in the Specific Aims. First, Core A procures (via interactions for clinical acquisition of samples via Core C), grows, and distributes well-differentiated primary human epithelial cells from a variety of tissue sources (lung, sinus, rectal, etc.) from CF and non-CF donors. This includes samples of cells from lung transplants, surgically excised nasal tissue, rectal biopsies, and nasal brushings obtained at UAB and from a large array of collaborating centers. Examination of novel expansion and differentiation techniques for primary cells is also a key function of the Core. Second, Core A conducts functional anatomic imaging of airway epithelia by 1-micron resolution Optical Coherence Tomography (μOCT) in vitro (primary cells of human or non-human origin) and ex vivo (intact full-thickness trachea, mainstem bronchi, and other tissues of human origin or comparable tissues from CF animal models, thus interfacing with Core B). μOCT allows for investigators to explore mucus flow and mucociliary interactions and is designated as a National Core due to its unique and important capabilities. Third, Core A performs and assists with measures of CFTR activity and expression. In addition to traditional assays of CFTR function (e.g, Ussing chambers), the Core supports innovative conductance assays, organoid swelling assays, and advanced PCR technology for investigating CFTR and other protein expression. Core A facilitates interdisciplinary collaborative research, provides resources that are beyond the expertise of individual research laboratories, fosters the sharing of ideas and experimental strategies, assists with technical troubleshooting, and maintains essential equipment that is and will be heavily utilized by P30 personnel and beyond. Cost savings are achieved by minimizing duplicate efforts of individual CF investigators, by the centralized purchase and usage of equipment, reagents, and supplies, as well as by maintaining a central repository for human epithelial tissue. On the whole, Core A provides significant expertise and resources to aid P30 investigators, fostering advancement of epithelial cell culture and innovative assays to understand CFTR pathogenesis and support rational drug discovery.

项目摘要/摘要：P30核心A 分化良好的人类呼吸道上皮细胞、模型系统和可用于它们的分析方法 是理解上皮生物学的工具性模型，并高度预测体内结果 临床试验。原代细胞可以与方法学结合使用，这些方法学可以容易地转化为呼吸道和 活体上皮功能，包括CFTR活性或其他离子转运体的测量，呼吸道表面液体 深度和粘液的水合，粘液的粘度和运输。上皮细胞模型进一步提供了一种极好的 检测呼吸道上皮炎症生物学的模型，这是囊性疾病发病机制的关键 纤维化(CF)肺部疾病。核心A的目的是支持众多P30调查人员的研究 这涉及细胞培养系统，并协助现有的和创新的分析方法来表征 细胞反应。 核心A履行具体目标中概述的三项主要职能。首先，核心A采购(通过互动 用于通过Core C)临床采集样本，培养和分布分化良好的原始人 来自各种组织来源(肺、鼻窦、直肠等)的上皮细胞来自合作伙伴和非合作伙伴捐助者的捐款。这 包括来自肺移植、手术切除的鼻组织、直肠活检和鼻腔的细胞样本。 从UAB和一大批协作中心获得的刷子。对小说扩展的审视 而原代细胞的分化技术也是核心的关键功能。第二，核心A进行 1微米分辨率光学相干断层扫描(μOCT)对呼吸道上皮细胞的功能解剖成像 体外(人或非人类来源的原代细胞)和体外(完整的全层气管，主干 支气管，以及人类起源的其他组织或来自CF动物模型的类似组织，从而与 核心B)。μOCT允许研究人员探索粘液流动和粘液纤毛相互作用，并被指定为 作为国家核心，由于其独特和重要的能力。第三，核心A执行并协助 CFTR活性和表达的测量。除了传统的CFTR功能分析(例如，Ussing 核心支持创新的电导分析、有机物肿胀分析和先进的聚合酶链式反应 研究cftr和其他蛋白质表达的技术。 核心A促进跨学科协作研究，提供超越专业知识的资源 单独的研究实验室，促进思想和实验策略的分享，协助技术 故障排除，并维护P30人员和将大量使用的基本设备 更远一点。成本节约是通过最大限度地减少个别CF调查员的重复工作来实现的，由 设备、试剂和用品的集中采购和使用，以及通过维护中央 人类上皮组织的储存库。总体而言，核心A提供了重要的专业知识和资源 帮助P30研究人员，促进上皮细胞培养和创新分析的进步，以了解 Cftr的发病机制，支持合理的药物发现。