CORE--CELL MODELS

核心--细胞模型

• 批准号: 7052594
• 负责人: WALTER E FINKBEINER
• 金额: $ 13.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052594
• 关键词: biomedical facility; cell bank /registry; cystic fibrosis; drug discovery /isolation; human tissue; metabolism disorder chemotherapy; respiratory epithelium; small molecule; tissue /cell culture

Basic pharmacological research aimed at identifying drugs that may correct the cellular derangements that lead to the debilitating and often fatal lung disease associated with cystic fibrosis requires a continuing and dependable source of cystic fibrosis and "normal" respiratory tissues. Cell culture techniques that allow the propagation of respiratory epithelial cells and formation of differentiated cell culture model systems provide a necessary and powerful tool for testing candidate drugs. Thus, the primary objective of the Cell Models Core is the collection of CF and non-CF respiratory tract tissues and the preparation of differentiated cultures of the respiratory surface epithelial cells and the tracheobronchial submucosal gland cells. A secondary objective of the Cell Models Core is to identify cell culture conditions that permit full expression of differentiated cellular functions, particularly in cell cultures that have been expanded by serial propagation. A tissue procurement system has been established for obtaining both CF and control nasal and airway tissues. Procured tissue is enzymatically digested, and liberated surface epithelial and submucosal gland acinar cells are established as cell cultures. The surface epithelial cells are studied as primary cell cultures of highly differentiated cell sheets that mimic the structure and function of the native nasal and airway epithelium. To increase the number of cell sheets available for screening compounds, some cell cultures are also expanded by serial propagation. The initial primary cultures of the tracheobronchial gland cells are expanded and then seeded as secondary cultures for experimental use. The conditions in which the passaged gland cells are grown are manipulated to produce cells expressing either a mucous or serous cell phenotype. Having respiratory epithelial cells derived from both the mucosal surface and the submucosal gland cells allows investigators to test candidate drugs for action in the various respiratory tract cells most affected in cystic fibrosis.

基础药理学研究旨在确定药物，可以纠正细胞 导致与囊性肺疾病相关的衰弱和通常致命的肺部疾病 纤维化需要持续和可靠的囊性纤维化来源和“正常”呼吸道疾病。 组织中允许呼吸道上皮细胞繁殖的细胞培养技术， 分化的细胞培养模型系统的形成提供了必要的和有力的工具， 测试候选药物因此，细胞模型核心的主要目的是收集CF和非CF呼吸道组织，并制备呼吸道表面上皮细胞和气管支气管粘膜下腺细胞的分化培养物。细胞模型核心的第二个目标是确定允许分化细胞功能完全表达的细胞培养条件，特别是在通过连续繁殖扩增的细胞培养物中。已经建立了用于获得CF和对照鼻和气道组织的组织获取系统。将获得的组织进行酶消化，并将释放的表面上皮和粘膜下腺泡细胞建立为细胞培养物。表面上皮细胞作为高度分化的细胞片的原代细胞培养物进行研究，这些细胞片模拟天然鼻和气道上皮的结构和功能。为了增加可用于筛选化合物的细胞片的数量，还通过连续繁殖来扩增一些细胞培养物。将气管支气管腺细胞的初始原代培养物扩增，然后接种作为实验用的二次培养物。操纵传代腺细胞生长的条件以产生表达粘液或浆液细胞表型的细胞。具有来自粘膜表面和粘膜下腺细胞的呼吸上皮细胞 允许研究人员测试候选药物在各种呼吸道细胞中的作用， 患有囊性纤维化