Core A: Cell Model and Evaluation Core

核心A：细胞模型和评估核心

基本信息

批准号：
10468804
负责人：
Bradford Alan Woodworth
金额：
$ 24.17万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468804
关键词：
Adopted Anatomy Animal Model Area Award Biological Assay Biology Bronchi Cell Culture System Cell Culture Techniques Cell model Cells Cellular Assay Clinical Trials Complement Complex Cost Savings Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Development Disease Dyes Epithelial Epithelial Cells Equipment Evaluation Evolution Fostering Frequencies Functional disorder Funding Gold Health Insurance Portability and Accountability Act Human Human Resources Hydration status Image In Situ In Vitro Individual Institutional Review Boards International Intervention Ion Transport Ions Laboratories Laboratory Research Lung Transplantation Measurement Measures Messenger RNA Methodology Methods Modeling Morbidity - disease rate Mucociliary Clearance Mucous body substance Nose Operative Surgical Procedures Optical Coherence Tomography Pathogenesis Pathway interactions Permeability Phenotype Process Property Pulmonary Cystic Fibrosis Reagent Reproducibility Research Research Design Research Personnel Research Support Resolution Resources Rights Safety Sampling Science Scientist Source Standardization Surface 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 cystic fibrosis patients digital drug discovery experience human subject improved in vivo innovation insight material transfer agreement mortality novel novel therapeutics protein expression quality assurance ranpirnase real-time images repository response sample fixation standard measure

项目摘要

PROJECT SUMMARY / ABSTRACT: P30 CORE A Well-differentiated primary human airway epithelial cells 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 function in vivo, including measures of CFTR activity or other ion transporters, airway surface liquid depth and mucus hydration, and mucus viscosity and transport. Primary airway cells 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, grows, and distributes well-differentiated primary human airway epithelial cells from CF and non-CF donors. This includes samples of cells from lung transplants, surgically excised nasal tissue, 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 or mainstem bronchi 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 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 分化良好的原代人气道上皮细胞以及可用于它们的检测方法是用于理解上皮生物学的仪器模型，并且高度预测临床体内结果原代细胞可以与容易转化为体内气道功能测定的方法一起使用，包括 CFTR 活性或其他离子转运体、气道表面液体深度和粘液的测量水合作用、粘液粘度和运输进一步提供了一个极好的模型。检查气道上皮炎症的生物学，这是囊性纤维化 (CF) 发病机制的关键 Core A 的目的是支持众多 P30 研究人员的研究。细胞培养系统，并协助建立和创新的分析方法来表征细胞回应。核心 A 执行具体目标中概述的三项主要职能：首先，核心 A 进行采购、种植和生产。分配来自 CF 和非 CF 供体的分化良好的原代人气道上皮细胞。来自阿拉巴马大学肺移植、手术切除的鼻组织和鼻刷的细胞样本以及来自大量合作中心的新颖扩展和分化技术的检查。对原代细胞进行功能解剖成像也是 Core 的一项关键功能。体外 1 微米分辨率光学相干断层扫描 (μOCT) 气道上皮细胞（人类原代细胞）或非人类来源）和离体（人类来源的完整全层气管或主支气管或来自 CF 动物模型的类似组织，因此与 Core B 接口允许研究人员探索粘液流动和粘液纤毛相互作用，并因其独特的和被指定为国家核心第三，核心 A 执行并协助 CFTR 活动和表达的测量。除了 CFTR 功能的传统测定（例如，Ussing 室）之外，该核心还支持创新用于研究 CFTR 和其他蛋白质表达的电导测定和先进 PCR 技术。核心A促进跨学科合作研究，提供超出专业知识的资源个人研究实验室，促进想法和实验策略的共享，协助技术排除故障并维护 P30 人员和将要大量使用的重要设备通过重复努力，最大限度地减少个别 CF 调查员，可以节省成本。设备、试剂和用品的集中采购和使用，以及维护一个中央总体而言，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 发病机制和支持合理的药物发现。