NATIONAL BIOREPOSITORY OF LUNG DISEASE-SPECIFIC HUMAN INDUCED PLURIPOTENT STEM CELLS:THE PURPOSE OF THIS RESOURCE IS TO BUILD AND SUPPORT A CRITICAL

肺病特异性人诱导多能干细胞国家生物库：该资源的目的是构建和支持关键的

• 批准号: 10834813
• 负责人: N/A N/A
• 金额: $ 65万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10834813
• 关键词: ABCA3 gene; BMPR2 gene; Blood Vessels; Boston; Cell Line; Cell Therapy; Cells; Clinical; Communities; Cystic Fibrosis Transmembrane Conductance Regulator; Development; Disease model; Drug Screening; Ensure; Epithelium; Fluorochrome; Future; Gene Mutation; Genes; Genetic; Human; Human Cloning; Immune; In Vitro; Induced Mutation; Knock-in; Lung; Lung diseases; Medical center; Methods; Mutation; National Heart, Lung, and Blood Institute; Organoids; Patients; Regenerative Medicine; Reporter; Reporter Genes; Research; Research Personnel; Resources; Scientist; Technology; Training Activity; Training Programs; Training and Education; Universities; Work; alpha 1-Antitrypsin; biobank; induced pluripotent stem cell; interstitial cell; lung development; lung regeneration; personalized therapeutic; quality assurance; tool

ABSTRACT This proposal seeks to support a formalized national resource for lung researchers consisting of a lung disease specific induced pluripotent stem cell (iPSC) biorepository that can be shared without restriction or exclusivity. More than 200 human lung disease-relevant iPSC lines, 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, SFTPC, SFTPB, ABCA3, and NKX2.1), but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. We propose to make the biorepository available to all researchers through formalized mechanisms that ensure: 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, curating, and maintaining an exhaustive panel of human 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, and c) continuation 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.

抽象的 该提案旨在支持肺部研究人员建立正式的国家资源，其中包括肺部疾病特异性诱导多能干细胞（iPSC）生物存储库，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) 现已储存超过 200 个与人类肺部疾病相关的 iPSC 系及其基因编辑后代，这为任何基础科学家提供了前所未有的机会，以获取源源不断的患者肺上皮细胞、血管细胞、免疫细胞或间质细胞。这些含有每位患者自身遗传背景的细胞现在可用于体外人类肺部疾病建模、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、SFTPC、SFTPB、ABCA3 和 NKX2.1 的位点突变），而且还携带通过最先进的基因编辑技术针对特定位点的敲入荧光染料报告基因。我们建议通过正式机制向所有研究人员提供生物样本库，以确保：a) iPSC 的全国共享 包括基础和临床肺研究人员都非常需要的关键资源，b) 建立质量保证方法和方法，用于存储、管理和维护未来几年大多数美国肺研究人员所需的携带最常见基因突变和肺谱系报告基因的详尽的人类品系组，以及 c) 继续开展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知识所需的专业知识 工具并将其分化为肺谱系。