A National Resource for Lung disease-specific iPS cells

肺病特异性 iPS 细胞的国家资源

基本信息

批准号：
8758308
负责人：
Darrell N. Kotton
金额：
$ 54.11万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-15 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8758308
关键词：
ABCA3 gene Adult Affect BMPR2 gene Biology Biomedical Research Blood Vessels Boston Cell Line Cell Therapy Cells Cellular biology Child Childhood Clinical Communities Cystic Fibrosis Transmembrane Conductance Regulator Databases Development Differentiated Gene Diffuse Disease Disease model Education Engineering Ensure Epithelial Epithelium Fluorochrome Foundations Freezing Funding Mechanisms Future Gene Mutation Genes Genetic Genetic Polymorphism Goals Hamman-Rich syndrome Human Human Cloning Immune In Vitro Individual Induced Mutation Knock-in Mouse Lung Lung diseases MUC5B gene Maintenance Medical center Methodology Methods Mission Morbidity - disease rate Mus Mutation Normal Statistical Distribution Patients Preclinical Drug Evaluation Pulmonary Cystic Fibrosis Pulmonary Fibrosis Reagent Regenerative Medicine Reporter Reporter Genes Research Research Infrastructure Research Personnel Resources Scientist Shipping Ships Source Syndrome Technology Therapeutic Training Training Programs Transgenic Organisms Undifferentiated Universities Vial device abstracting alpha 1-Antitrypsin alpha 1-Antitrypsin Deficiency base cell bank design gene cloning induced pluripotent stem cell interstitial interstitial cell lung regeneration mortality open source primary pulmonary hypertension programs public health relevance quality assurance self-renewal stem cell technology therapeutic development tool web page

项目摘要

DESCRIPTION (provided by applicant): This proposal seeks to estabalish a formalized national resource for lung researchers consisting of a lung disease-specific induced pluripotent stem cell (iPSC) bank that can be shared without restriction or exclusivity. More than 200 human lung disease-relevant iPSC clones, and their gene-edited progeny, are now banked in the Center for Regenerative Medicine (CReM) of Boston University/Boston Medical Center, providing an unprecedented opportunity for any basic scientist to derive an inexhaustible supply of patient-derived lung epithelial, vascular, immune, or interstitial cells. These cells containing each patient's own genetic background are now available for in vitro human lung disease modeling, drug screening of personalized therapeutics, and the development of future lung regeneration cell-based therapies. The most valuable human clones in this bank not only carry the most common lung disease-inducing mutations (e.g. mutations in loci encoding CFTR, Alpha-1 antitrypsin, BMPR2, SPC, SPB, ABCA3, and NKX2.1), but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. In parallel, the bank also includes 50 mouse iPSC clones generated from transgenic or knock-in mice that carry well characterized fluorochrome reporters of lung lineages (SPC-GFP, T1a-GFP, Tie2-GFP, SMA-GFP, and Nkx2.1-GFP). We propose to establish this cell bank through four specific aims to accomplish the goals of: a) national sharing of iPSCs that comprise a critical resource in high demand by both basic and clinical lung researchers, b) establishment of quality assurance approaches and methods for banking an exhaustive panel of human and mouse lines carrying the most common gene mutations and lung lineage reporter genes required by the majority of U.S. lung researchers in the years ahead, c) development of a formalized education and training program able to nationally disseminate the expertise required to fully harness these new tools and differentiate them into lung lineages, and d) self-sustained maintenance of the bank financially, logistically, and educationally.

描述（由申请人提供）：该提案旨在为肺部研究人员建立一个正式的国家资源，其中包括一个肺部疾病特异性诱导多能干细胞（iPSC）库，可以不受限制或排他性地共享。波士顿大学/波士顿医学中心再生医学中心 (CReM) 现已储存 200 多个与人类肺部疾病相关的 iPSC 克隆及其基因编辑后代，这为任何基础科学家提供了前所未有的机会，以获取取之不尽用之不竭的信息。供应源自患者的肺上皮细胞、血管细胞、免疫细胞或间质细胞。这些细胞含有现在，每个患者自己的遗传背景都可用于体外人类肺部疾病模型、个性化治疗的药物筛选以及未来基于肺再生细胞的疗法的开发。该库中最有价值的人类克隆不仅携带最常见的肺部疾病诱发突变（例如编码 CFTR、Alpha-1 抗胰蛋白酶、BMPR2、SPC、SPB、ABCA3 和 NKX2.1 的位点突变），而且还携带敲击-通过最先进的基因编辑技术针对特定位点的荧光染料报告基因。与此同时，该库还包括 50 个由转基因或敲入小鼠产生的小鼠 iPSC 克隆，这些小鼠携带肺谱系特征明确的荧光染料报告基因（SPC-GFP、T1a-GFP、Tie2-GFP、SMA-GFP 和 Nkx2.1-绿色荧光蛋白）。我们建议通过四个具体目标来建立这个细胞库，以实现以下目标：a）国家共享 iPSCs 是基础和临床肺部研究人员急需的关键资源，b) 建立质量保证途径和方法，用于储存携带最常见基因突变和肺谱系报告基因的详尽的人类和小鼠品系。大多数美国肺研究人员在未来几年，c）制定正式的教育和培训计划，能够在全国范围内传播充分利用这些新工具并将其区分为肺谱系所需的专业知识，以及d）自我持续维护银行财务、后勤和教育方面。