Cell & Tissue Models

细胞

基本信息

批准号：
9284465
负责人：
WALTER E FINKBEINER
金额：
$ 18.11万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9284465
关键词：
3-Dimensional Air Autopsy B-Lymphocytes Basic Science Biological Assay Biological Models Bioreactors Cell Count Cell Culture Techniques Cell Line Cell Separation Cell model Cell physiology Cells Collection Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Development Dimensions Disease Drug Modelings Effectiveness Engineering Ensure Environment Epithelial Epithelial Cells Epithelium Evaluation Excision Exhibits Foundations Fresh Tissue Functional disorder Generations Genotype Gland Goals Human Intestinal Mucosa Intestines Investigation Ion Transport Lead Liquid substance Lung Lung Transplantation Methods Modeling Mucins Mutation Nasal Polyps Nose Operative Surgical Procedures Organ Organoids Patients Pharmaceutical Preparations Polypectomy Production Property Quality Control Research Research Infrastructure Research Personnel Research Project Grants Resources Respiratory System Respiratory tract structure Second Pregnancy Trimester Serial Passage Source Stem cells Structure of parenchyma of lung Surface Termination of pregnancy Testing Therapeutic Tissue Model Tissue Sample Tissues Tracheobronchial Translational Research Translations Transplantation abortion airway surface liquid base clinical material cystic fibrosis airway drug candidate drug discovery high throughput screening human tissue immortalized cell improved in vitro Model instrumentation interest model development neoplastic cell novel novel therapeutic intervention personalized medicine pre-clinical ranpirnase respiratory screening small molecule small molecule therapeutics therapeutic evaluation

项目摘要

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.

抽象的细胞和组织模型核心（核心B）的主要目标是支持CF药物发现的工作通过提供最先进的CF，相关的细胞和组织模型来参与研究人员。超过20 此续签中描述的项目将将核心B用于细胞和/或组织模型。这些模型用于高通量筛选测定，铅化合物的测试，治疗相关的临床前生物测定法，以及CF和气道病理生理学的转化科学研究。细胞和组织核心达到通过基础设施收集与CF相关的时机的目标；仪器和细胞专业知识隔离，文化，存储和质量控制；新型细胞培养方法的适应和发展；和细胞模型和组织向CF研究者的方便分布。高度分化的平面细胞模型呼吸道表面上皮细胞和粘膜下腺细胞，这些细胞复制天然离子转运，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。此外我们在提供这些模型方面的悠久力量，核心已在三维方面发展了专业知识器官模型（器官），旋转壁血管生物反应器培养物和有条件重编程的细胞。器官和旋转壁血管生物反应器培养物提供了类似组织的环境，可以鼓励细胞分化。两种方法都可能增加每个组织样品可用的培养单元数量产生更有效的，疾病与疾病发现的模型。有条件重新编程的细胞允许通过串行传递来扩展CF细胞，可以增加CF细胞模型的产生和开发更有效的测定法以评估小分子。使用有条件的重新编程从有限数量的稀有CF基因型的细胞中产生更多的细胞模型将有助于开发“个性化”疗法。