Core 2: Lung Tissue Core

核心2：肺组织核心

• 批准号: 10262934
• 负责人: Mauricio Rojas
• 金额: $ 13.87万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10262934
• 关键词: 3-Dimensional; Address; Age; Animal Model; Animals; Autopsy; Biological; Biological Models; Biomechanics; Bone Marrow; Bone Marrow Stem Cell; Cells; Clinical Data; Clinical Trials; Collaborations; Collection; Comparative Study; Complex; Consultations; DNA; Disease; Distal; Endothelial Cells; Epithelial Cells; Evaluation; Fibroblasts; Genomics; Goals; Histopathology; Housing; Human; Individual; Infection; Inflammation; Institution; Investigation; Knowledge; Lung; Lung Transplantation; Mesenchymal Stem Cells; Modeling; Molecular; Mus; Organ; Organ Culture Techniques; Organ Donor; Organ Procurements; Pathogenesis; Pathology; Pathway interactions; Patients; Perfusion; Pharmacotherapy; Population; Proteins; Protocols documentation; Pulmonary artery structure; RNA; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Sepharose; Skin; Smooth Muscle Myocytes; Source; Specimen; Standardization; Structure of parenchyma of lung; System; Systemic Scleroderma; Techniques; Testing; Therapeutic; Therapeutic Intervention; Time; Tissue Embedding; Tissue Model; Tissue Sample; Tissues; Translational Research; Transplant Recipients; Transplantation; Trauma; Universities; base; biobank; design; efficacy testing; ex vivo perfusion; experimental study; hemodynamics; human disease; human model; improved; mouse model; novel; novel therapeutics; pre-clinical; preclinical study; programs; pulmonary function; response; stem cells; synergism; systemic inflammatory response; therapeutic candidate; therapeutic evaluation; tool; translational model; translational study; vertebra body

Core 002 - Abstract In this revised version we had actualize the role of lung tissue core and the numbers of samples collected. This core will be compromise by three centralized subcores, each of which is essential to reach the goals of this program application. The Core includes, a bio-bank sub- core collecting biological samples from patients and organ donors through the University of Pittsburgh, an ex-vivo lung perfusion sub-core, to study lung function, pathology, and hemodynamics of lungs maintained under ex-vivo perfusion, and an ex-vivo 3-D human lung tissue model sub-core, to generate sections of lung tissue that can be culture for long periods of time. All three components are essential for the mechanistic and translational research goals of this Program application. The Specific Aims for the Core are: 1. To enrich our current biorepository of lung, skin and bone marrow stem cells procured from normal individuals and individuals with SSc. 2. To assist program investigators in the design and implementation of experiments using biological specimens from the biobank. Research Plan: The bio-bank will provide tissue samples of lung, skin and bone marrow stem cells procured from normal individuals and individuals with SSc. We will include the collection of lung and skin fibroblasts, bone marrow derived stem cells, endothelial cells, and smooth muscle cells, as well as tissue samples for RNA, DNA, protein and histopathology analyses. The ex-vivo lung perfusion sub-core will provide a preclinical translational model for the test of therapeutic candidates. The ex-vivo 3-D human lung tissue model sub-core will provide a collection of pulmonary arteries for biomechanical analyses, and agarose embedded tissue for ex-vivo 3D lung organ culture. Significance and synergy: Comparative studies between human and mice of responses to systemic inflammation demonstrate marked differences and poor correlations between the two species, confirming the difficulties in the use of animal models to mimic human diseases. There is a need of more preclinical studies using human specimens to answer fundamental questions in complex diseases such as systemic sclerosis. All Research Projects will use resources of the lung tissue core to: 1) test mechanistic hypotheses of the pathogenesis of SSc, 2) test the efficacy of new therapeutics in established ex vivo lung perfusion model and 3-D human lung tissue model, and 3) evaluate molecular mechanisms in human biological samples.

核心 002 - 摘要 在这个修订版本中，我们认识到了肺组织核心的作用以及肺组织核心的数量。 收集的样本。该核心将由三个集中式子核心组成，每个子核心 对于实现该计划应用程序的目标至关重要。核心包括生物库子系统 通过大学从患者和器官捐赠者那里收集生物样本的核心 匹兹堡，一个离体肺灌注子核心，用于研究肺功能、病理学和 离体灌注下维持的肺的血流动力学，以及离体 3-D 人肺 组织模型子核心，生成可长期培养的肺组织切片 一段时间。所有三个组成部分对于机械和转化都是必不可少的 本计划申请的研究目标。 核心的具体目标是： 1. 丰富我们目前的肺、皮肤生物库 以及从正常个体和 SSc 个体获得的骨髓干细胞。 2. 至 协助项目研究人员设计和实施生物实验 来自生物银行的标本。 研究计划：生物库将提供肺、皮肤和骨骼的组织样本 骨髓干细胞取自正常个体和 SSc 个体。我们将包括 肺和皮肤成纤维细胞、骨髓干细胞、内皮细胞的集合， 和平滑肌细胞，以及用于 RNA、DNA、蛋白质和组织病理学的组织样本 分析。离体肺灌注子核心将提供临床前转化模型 用于测试候选治疗药物。离体3D人体肺组织模型子核心 将提供用于生物力学分析的肺动脉集合和琼脂糖 用于离体 3D 肺器官培养的包埋组织。 意义和协同作用：人类和小鼠之间的比较研究 对全身炎症的反应表现出明显的差异和较差的相关性 两个物种之间的研究，证实了使用动物模型来模拟的困难 人类疾病。需要使用人体标本进行更多临床前研究 回答系统性硬化症等复杂疾病的基本问题。所有研究 项目将利用肺组织核心的资源来：1）测试肺组织核心的机制假设 SSc 的发病机制，2) 测试新疗法在已建立的离体肺中的功效 灌注模型和 3-D 人体肺组织模型，3) 评估分子机制 人类生物样本。