Core 2: Lung Tissue Core

CORE 002-摘要 在这个修订版中，我们实现了肺组织核心的作用和肺组织核心的数量 收集的样本。该核心将被三个集中式子核折衷，每个子核 对于实现本计划应用程序的目标至关重要。核心包括，一个生物库子库- 通过科罗拉多大学从患者和器官捐赠者那里收集生物样本 匹兹堡，一个体外肺灌注亚核心，研究肺功能，病理，和 在体外灌流条件下维持肺血流动力学，以及体外三维人体肺 组织模型亚核，以生成可长期培养的肺组织切片 一段时间。所有这三个组件对于机械和平移都是必不可少的 本计划申请的研究目标。 核心的具体目标是：1.丰富我们现有的肺、皮肤生物库 取自正常人和自闭症患者的骨髓干细胞。2.至 协助项目调查人员设计和实施使用生物学的实验 生物库的标本。 研究计划：生物库将提供肺、皮肤和骨的组织样本 骨髓干细胞取自正常人和自闭症患者。我们将包括 收集肺和皮肤成纤维细胞，骨髓来源的干细胞，内皮细胞， 以及组织样本的RNA、DNA、蛋白质和组织病理学 分析。体外肺灌注亚核将提供一个临床前的翻译模型 用于治疗候选药物的测试。体外三维人体肺组织模型亚核心 将提供一组用于生物力学分析的肺动脉，以及琼脂糖凝胶 包埋组织用于体外三维肺器官培养。 意义与协同作用：人与小鼠的比较研究 对全身炎症的反应表现出显著的差异和较差的相关性 在这两个物种之间，证实了使用动物模型来模拟的困难 人类疾病。需要更多的临床前研究，使用人类标本来 回答系统性硬化症等复杂疾病的基本问题。所有研究 项目将使用肺组织核心的资源来：1)测试 SSC的发病机制，2)检测新疗法对已建立的体外肺的疗效 血流灌注模型和三维人体肺组织模型；3)评价分子机制。 人类生物样本。

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.