Core--Cell Culture Models

核心--细胞培养模型

• 批准号: 6774600
• 负责人: Scott H Randell
• 金额: $ 14.09万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6774600
• 关键词: animal tissue; biological models; biomedical facility; cystic fibrosis; human tissue; liver cells; respiratory epithelium; sample collection; tissue /cell culture; vascular endothelium

Cell cultures are instrumental for studying basic and applied aspects of gene and molecular therapy relevant to the treatment of cystic fibrosis (CF). Specifically, human airway epithelial cell cultures maintained at an air-liquid interface and displaying mucociliary differentiation similar to the in vivo epithelium faithfully reproduce the high resistance to gene therapy vectors characteristic of the native human mucosa. These cultures are an excellent model to better understand vector interaction with target cells and provide a strong platform for pre-clinical basic science studies to address issues crucial to the success of gene and molecular therapy for CF. A Tissue Procurement and Cell Culture Core was established at the University of North Carolina (UNC) in 1984, under the auspices of the CF Foundation, to provide standardized cell cultures to CF researchers. The Core has supported UNC Gene Therapy for CF projects since 1993 and has increased its output and capabilities to meet growing research demands. The Core routinely makes available cells and media that are unavailable and/or prohibitively expensive if purchased from commercial suppliers. The historical focus of the Core has been to provide human airway epithelial cell cultures to UNC CF Center investigators. The purpose of the present application is to increase the range of services to the University-wide gene and molecular therapy community by providing human airway epithelial cells in environments more representative of in vivo conditions as well as supplying additional cell types. To accomplish these goals, we propose the following specific aims. 1) To provide well differentiated, normal and CF, large and small airway epithelial cells in novel model systems reproducing important elements of the in vivo airway environment. 2) To provide newly developed, well-differentiated mouse airway epithelial cell cultures suitable for mechanistic studies. 3) To cost effectively provide human pulmonary artery and lung microvascular endothelial cells and hepatocytes, high priority targets for gene therapy. Through these functions, and in conjunction with the other Cores in this application, the Cell Culture Models Core will foster collaborations directed at improving vector efficiency to both the airway epithelium and additional cell and organ systems relevant to the research mission of NIDDK.

细胞培养物对研究基因和分子治疗的基本和应用方面具有重要作用，与囊性纤维化治疗有关（CF）。具体而言，人类气道上皮细胞培养物保持在空气界面上，并显示出类似于体内上皮的粘膜钙化差异化，从而忠实地再现了对本地人类粘膜的基因治疗载体的高耐药性。这些培养物是更好地了解与靶细胞的矢量相互作用的绝佳模型，并为临床前基础科学研究提供了一个强大的平台，以解决对基因和分子成功至关重要的问题 CF的治疗。 1984年，在CF基金会的主持下，在北卡罗来纳大学（UNC）建立了组织采购和细胞培养核心，为CF研究人员提供了标准化的细胞培养。该核心自1993年以来一直支持CF项目的UNC基因疗法，并提高了其产量和能力，以满足不断增长的研究需求。核心通常会使如果从商业供应商那里购买，则无法获得和/或过于昂贵的细胞和媒体。核心的历史重点是向UNC CF中心研究人员提供人类气道上皮细胞培养物。本应用的目的是通过在环境中提供人类气道上皮细胞来增加大学范围的基因和分子疗法社区的服务范围 更多代表体内条件以及提供其他细胞类型。为了实现这些目标，我们提出以下特定目标。 1）在新型模型系统中提供良好的分化，正常和小型气道上皮细胞，重现了体内气道环境的重要元素。 2）提供新开发的，分化良好的小鼠气道上皮细胞培养物，适合机械研究。 3）为了有效地提供人类肺动脉和肺微血管内皮细胞和肝细胞，基因治疗的高优先靶标。通过这些 功能，以及与本应用程序中的其他核心结合在一起，细胞培养模型核心将促进旨在提高载体上皮的矢量效率以及与NIDDK研究任务相关的其他细胞和器官系统的协作。