Cell & Tissue Models

摘要 细胞和组织模型核心（核心B）的主要目标是支持CF药物发现工作， 通过提供最先进的CF相关细胞和组织模型，帮助参与研究的研究人员。20多 本更新中描述的项目将使用Core B用于细胞和/或组织模型。这些模型用于 高通量筛选测定，先导化合物的测试，治疗相关的临床前生物测定， 以及CF和气道病理生理学的转化科学研究。细胞和组织核心实现 其目标是通过收集CF相关组织的基础设施;细胞检测的仪器和专业知识， 分离、培养、储存和质量控制;适应和开发新的细胞培养方法;以及 方便地将细胞模型和组织分发给CF研究者。高度分化的平面细胞模型 复制天然离子转运的呼吸道表面上皮细胞和粘膜下腺细胞，气道 表面液体形成和粘蛋白分泌仍然是核心提供的主要细胞模型。除了 我们在提供这些模型方面的长期实力，核心已经开发了三维的专业知识， 器官型模型（类器官）、旋转壁容器生物反应器培养物和条件性重编程细胞。 类器官和旋转壁容器生物反应器培养物提供了一个组织样环境， 分化这两种方法都可能增加每个组织样本可用的培养单位数量 产生更有效的、与疾病相关的药物发现模型。突触重编程细胞 通过连续传代扩增CF细胞，允许增加CF细胞模型的产量， 开发用于评估小分子的更有效的测定法。使用条件重编程 从有限数量的表现出罕见CF基因型的细胞产生更多的细胞模型将有助于 发展“个性化”治疗。

ABSTRACT   The primary objective of the Cell & Tissue Models Core (Core B) is supporting the CF drug discovery efforts of participating investigators by providing state-of-the-art, CF-relevant cell and tissue models. More than 20 projects described in this renewal will utilize Core B for cell and/or tissue models. These models are used in high throughput screening assays, testing of lead compounds, therapeutically relevant preclinical bioassays, and translational science investigations of CF and airway pathophysiology. The Cell & Tissues Core achieves its objective via an infrastructure for the collection of CF-relevant tissues; instrumentation and expertise for cell isolation, culture, storage and quality control; adaptation and development of novel cell culture methods; and convenient distribution of cell models and tissues to CF investigators. Highly differentiated planar cell models of respiratory tract surface epithelial cells and submucosal gland cells that replicate native ion transport, airway surface liquid formation and mucin secretion remain the major cell model provided by the Core. In addition to our long-established strength in providing these models, the core has developed expertise in three-dimensional organotypic models (organoids), rotary wall vessel bioreactor cultures and conditionally reprogrammed cells. Organoids and rotary wall vessel bioreactor cultures provide a tissue-like environment that encourages cellular differentiation. Both methods increase the number of culture units available per tissue sample potentially generating more efficient, disease-relevant models for drug discovery. Conditionally reprogrammed cells allow expansion of CF cells through serial passaging allowing increased production of CF cell models and development of more efficient assays for evaluating small molecules. Using conditional reprogramming for producing more cell models from limited numbers of cells exhibiting rare CF genotypes will aid the development of “personalized” therapies.