Human Core

人类核心

• 批准号: 10198010
• 负责人: Barry R Stripp
• 金额: $ 40.75万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198010
• 关键词: Allografting; Biological; Biological Preservation; Bronchoscopy; Cell Fraction; Cell Fractionation; Cell Separation; Cell physiology; Cells; Cessation of life; Chronic; Cicatrix; Clinical Research; Collaborations; Collection; Computer software; Data; Data Collection; Databases; Deposition; Diagnosis; Disease; Dissociation; Endothelial Cells; Enrollment; Epithelial; Epithelial Cells; Extracellular Matrix; Fibroblasts; Functional disorder; Future; Generations; Genomics; Hematopoietic; Human; Human Resources; Human Subject Research; Infrastructure; Laboratory Personnel; Libraries; Link; Liquid substance; Lung; Lung Transplantation; Measures; Mesenchymal; Mesenchyme; Messenger RNA; Microfluidics; Operating Rooms; Outcome; Patients; Population; Preparation; Process; Proteins; Pulmonary Fibrosis; Registries; Research; Research Personnel; Research Project Grants; Research Support; Resources; Safety; Sampling; Sampling Studies; Severity of illness; Specimen; Standardization; Stromal Cells; Structure of parenchyma of lung; Suspensions; System; Therapeutic; Therapeutic immunosuppression; Time; Tissues; Transplantation; biobank; cell type; clinical phenotype; data quality; experience; experimental study; fibrogenesis; human subject; idiopathic pulmonary fibrosis; longitudinal database; lung allograft; lung volume; magnetic beads; mesenchymal stromal cell; molecular phenotype; post-transplant; prevent; programs; prospective; pulmonary function; recruit; response; sample collection; single-cell RNA sequencing; transcriptome; transcriptome sequencing; transplant registry

Project Summary/Abstract Idiopathic pulmonary fibrosis (IPF) and chronic lung allograft dysfunction (CLAD) are disorders characterized by the inexorable loss of lung function and death within 3-5 years of diagnosis. IPF and CLAD share features of relentless extracellular matrix (ECM) deposition and the lack of response to immunosuppressive therapy. Compelling preliminary evidence is presented in the 3 projects within this proposal that the progressive scarring inherent to both IPF and CLAD is the consequence of dysregulated crosstalk between the lung epithelium and the lung resident mesenchymal stromal cells. Although there are clear distinctions between mechanisms of IPF and CLAD, this common theme should be investigated for potential therapeutic benefit in each condition. Each of the 3 inter-related projects proposed in this application is strengthened by studies in human subjects including the collection of patient specimens. We propose a Human Core to facilitate the safe and efficient collection of research data and specimens from these human subjects. We will leverage access to the large UCLA lung transplant program to supply high-quality human samples for the 3 program projects in this application. Specifically, we will recruit and enroll 300 subjects listed for lung transplant, for any indication, to participate in a post-transplant registry and bronchoscopy sample study proposed in Project 3. Among these 300 subjects, those with a diagnosis of IPF will be recruited to also provide their explanted IPF lung tissues for Projects 1 and 2. All subjects will be entered into a registry and the samples will be linked to this robust longitudinal database for clinical phenotyping. The Human Core comprises an experienced team of investigators, clinical research staff and laboratory personnel who will support human subject research and biological sample collection and processing for each of the 3 projects. This team has successful collaboration across multiple projects during the past 5 years. Therefore, the combination of a high volume lung transplant program, investigators' expertise, and an established infrastructure for human subject research and sample collection, collectively amount to a one-of-a-kind resource to study IPF and CLAD.

项目总结/摘要 特发性肺纤维化（IPF）和慢性肺移植物功能障碍（CLAD）是以 肺功能的无情丧失和诊断后3-5年内的死亡。IPF和CLAD共享功能 细胞外基质（ECM）的无情沉积和免疫抑制治疗缺乏反应。 令人信服的初步证据是在3个项目中提出的这一建议， IPF和CLAD固有的瘢痕形成是肺间串扰失调的结果， 上皮和肺驻留间充质基质细胞。虽然有明确的区别， IPF和CLAD的机制，应研究这一共同主题的潜在治疗获益， 每个条件。本申请书所建议的三个互相关连的项目，均透过下列研究予以加强： 人类受试者，包括患者标本的采集。我们建议使用人类核心来促进安全 以及从这些人类受试者中有效收集研究数据和标本。我们将利用 大型加州大学洛杉矶分校肺移植计划，为3个计划项目提供高质量的人体样本， 这个应用程序。具体而言，我们将招募并入组300例肺移植受试者，用于任何适应症， 参与项目3中提出的移植后登记和支气管镜检查样本研究。其中 将招募300例诊断为IPF的受试者，并提供其经鉴定的IPF肺组织， 项目1和2。所有受试者都将进入登记研究，样本将与该稳健的 临床表型的纵向数据库。人力核心由经验丰富的团队组成， 支持人类受试者研究的研究者、临床研究人员和实验室人员， 为3个项目中的每个项目收集和处理生物样本。这个团队有着成功的合作 在过去的五年里，在多个项目中。因此，结合大容量肺移植 计划，研究人员的专业知识，以及人类受试者研究和样本的既定基础设施 集合，共同构成了研究IPF和CLAD的独一无二的资源。