INJURED LUNG AND ITS INFLUENCE ON MARROW CELL PHENOTYPE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project will examine cell-to-cell communication between injured lung cells and bone marrow cells and mechanisms by which this communication aids in marrow cell-based lung repair of lung injury. Research from our laboratory has demonstrated that adult bone marrow cells home to injured murine lung and participate in the restoration of lung cells. We hypothesize that injured lung cells induce epigenetic modifications of marrow cells by release from lung cells and subsequent uptake by marrow cells of lung cell-derived microvesicles, thereby inducing marrow cells to assume a lung cell phenotype. The specific aims are to: 1. Define marrow cell populations which take up lung-derived microvesicles, focusing on whole bone marrow cells, various marrow-derived differentiated cells and purified hematopoietic stem/progenitor cells, and define the persistence of these phenotypic changes. 2. Determine how lung-derived microvesicles gain entry into marrow cells and how they influence the phenotype of these cells. 3. Define the influence of cell cycle on the ability of marrow cells to take up lung-derived microvesicles. 4. Determine if transplantation of marrow cells that have taken up lung-derived microvesicles or microvesicles themselves participate in the pathogenesis of murine models of pulmonary hypertension. Ultimately, we wish to demonstrate that marrow cells possess sufficient reparative properties to provide a novel therapeutic option for pulmonary diseases with few currently effective treatments.