A National iPS Cell Network with Deep Phenotyping for Translational Research

具有深度表型分析功能的国家 iPS 细胞网络，用于转化研究

基本信息

批准号：
9214660
负责人：
Chad Albert Cowan
金额：
$ 90.51万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9214660
关键词：
American Biology Blood specimen Boxing Cataloging Catalogs Cell Culture Techniques Cell Line Cell Lineage Cell Therapy Cells Clinical Collection Communities Consent Derivation procedure Development Differentiated Gene Disease Disease model Education Fluorochrome Framingham Heart Study Funding Mechanisms Future Generations Genes Genetic Genetic Polymorphism Genotype Goals Human Human Cell Line Human Cloning Human Genome In Vitro Individual Knock-in Laboratories Lung Maintenance Methodology Mission Mutation Participant Patients Phenotype Population Preclinical Drug Evaluation Protocols documentation Reagent Reporter Research Research Infrastructure Research Personnel Resources Sampling Scientist Site Source Techniques Technology Training Training Programs Translational Research abstracting advanced disease base body system cell bank cohort design gene cloning genetic manipulation genome editing human disease induced pluripotent stem cell open source personalized therapeutic programs regenerative repository therapeutic development tool web page

项目摘要

Project Summary/Abstract The discovery of iPSCs provides an unprecedented opportunity for any scientist to derive an inexhaustible supply of patient-derived primary cells. These cells containing each patient's own genetic background can now be applied for in vitro human disease modeling, drug screening of personalized therapeutics, and the development of future regenerative cell-based therapies. The most valuable human clones already generated by the CTSA investigators collaborating on this proposal not only carry common disease-associated mutations and polymorphisms, but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. The goal of this proposal is the establishment of a CTSA network of induced pluripotent stem cell (iPSC) repositories and iPSC cores that will enable advanced disease modeling using >1000 existing normal and disease specific human cell lines and banking 6,000 additional samples procured from the 2nd and 3rd generation participants of the Framingham Study. A concerted effort for curation, sharing, and distribution of this vital resource across all CTSAs does not exist. This proposal thus creates a CTSA iPSC Network led by teams who have championed an `Open Source Biology' approach, freely sharing iPSC lines and their reprogramming reagents with more than 500 labs to date across the globe. Its goals are to make patient-derived iPSCs together with the tools and expertise for their genetic manipulation available to the greater research community on a large scale to realize their promise for extending understanding of disease and developing potential therapies. To achieve these goals, it proposes: a) national sharing of >1000 iPSC lines already derived by the CTSA teams collaborating in this proposal, representing a critical resource in high demand by both basic and clinical researchers, b) development and support of formalized education and training programs able to nationally disseminate the expertise required to fully harness these new tools and differentiate them into the wide diversity of human cell lineages, c) maintenance and sharing of open source gene-editing tools and gene edited iPSC lines that will enable CTSA investigators to manipulate the human genome at will, and d) derivation for national sharing of additional iPSC lines generated from the most densely clinically and genetically phenotyped cohort of individuals currently followed in the USA today: the ~6,000 participants of the second and third generations of the Framingham Study.

项目摘要/摘要 IPSC的发现为任何科学家提供了一个前所未有的机会无尽的患者衍生原代细胞的供应。这些包含每个患者自己的遗传的细胞现在可以将背景应用于体外人类疾病建模，个性化药物筛查疗法，以及未来再生细胞疗法的发展。最有价值的人 CTSA调查人员已经在此提案上合作的克隆不仅携带了共同的克隆与疾病相关的突变和多态性，但也带有荧光型报告者通过最先进的基因编辑技术针对特定基因座。该提议的目的是建立了诱导多能干细胞（IPSC）存储库的CTSA网络和 IPSC核心将使用> 1000现有的正常和疾病实现晚期疾病建模从第二和第三购买的特定人类细胞系和银行收集了6,000个其他样品 Framingham研究的一代参与者。在所有CTSA中的策划，共享和分发这一重要资源的共同努力并没有存在。因此，该建议创建了一个由倡导开放的团队领导的CTSA IPSC网络来源生物学的方法，自由地共享IPSC线及其重编程试剂的方法超过迄今为止，全球500个实验室。它的目标是将患者衍生的IPSC与工具一起制作以及针对大型研究社区提供的基因操纵的专业知识实现他们对扩展对疾病并发展潜在疗法的承诺。到实现这些目标，它提出：a）CTSA已经得出的> 1000 IPSC线的国家共享在此提案中合作的团队，代表基本和基本和临床研究人员，b）制定和支持正式的教育和培训计划全国范围内传播充分利用这些新工具并将其区分成的专业知识人类细胞谱系的广泛多样性，c）维护和共享开源基因编辑工具基因编辑了IPSC系列，该线路将使CTSA研究人员随意操纵人类基因组， d）派生用于全国共享临床最密集的IPSC系列的其他IPSC线以及当前在美国当前遵循的个体的基因表型队列：约6,000 弗雷明汉研究第二和第三代的参与者。