Core 2: Lung Tissue Core

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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.