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 通过提供最先进的、与CF相关的细胞和组织模型来参与研究。超过20个 本次续订中描述的项目将使用Core B进行细胞和/或组织模型。这些型号用于 高通量筛选分析，先导化合物测试，与治疗相关的临床前生物分析， 以及对慢性阻塞性肺疾病和呼吸道病理生理学的翻译科学研究。细胞和组织核心的实现 其目标是通过收集与CF相关的组织的基础设施；用于细胞的仪器和专业知识 分离、培养、储存和质量控制；适应和发展新的细胞培养方法；以及 方便地将细胞模型和组织分发给CF研究人员。高分化平面细胞模型 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，呼吸道 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……之外 我们在提供这些模型方面的长期实力，核心已经开发出了专业的三维 器官模型(类有机物)、旋转壁容器生物反应器培养和条件重编程细胞。 有机化合物和旋转壁式生物反应器培养提供了一个组织样的环境，促进了细胞 差异化。这两种方法都有可能增加每个组织样本的培养单位数量 为药物发现生成更有效的、与疾病相关的模型。有条件地重新编程的单元允许 通过连续传代扩大CF细胞，从而增加CF细胞模型和 开发更有效的小分子评估方法。使用条件重编程实现 从数量有限的显示罕见CF型的细胞中生产更多的细胞模型将有助于 发展“个人化”疗法。

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.