Core 2: Lung Tissue Core

核心002 -摘要 在这个修订版本中，我们实现了肺组织核心的作用， 采集的样本。该核心将由三个集中的子核心折衷，每个子核心 对于实现本计划的目标至关重要。核心包括一个生物银行子银行， 核心收集生物样本从病人和器官捐赠者通过大学 匹兹堡，一个离体肺灌注子核心，研究肺功能，病理学， 在离体灌注下维持的肺的血液动力学和离体3-D人肺 组织模型子核心，以生成可以长期培养的肺组织切片 一段时间。所有这三个组成部分是必不可少的机械和翻译 本计划申请的研究目标。 核心的具体目标是：1。丰富我们当前的肺部、皮肤生物库 以及从正常个体和患有SSc的个体获得的骨髓干细胞。2.到 协助项目研究人员设计和实施生物学实验， 生物样本库里的样本 研究计划：生物库将提供肺、皮肤和骨骼的组织样本 从正常个体和患有SSc的个体获得的骨髓干细胞。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， 以及用于RNA、DNA、蛋白质和组织病理学的组织样品 分析。离体肺灌注子核心将提供临床前转化模型 用于治疗候选人的测试。离体三维人体肺组织模型子核心 将为生物力学分析提供肺动脉的集合， 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 对全身性炎症的反应表现出显著的差异和较差的相关性 这两个物种之间的差异，证实了使用动物模型来模拟 人类疾病。需要更多的临床前研究，使用人体标本， 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：1）测试肺组织的机制假设。 2）在建立的离体肺中测试新疗法的功效 灌注模型和3-D人肺组织模型，和3）评估在肺组织中的分子机制。 人体生物样本

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.