This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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: 1. We will define marrow cell populations which take up lung-derived microvesicles, focusing on whole bone marrow cells and various populations of hematopoietic stem cells. 2. We will define the influence of cell cycle on the ability of marrow cells to take up lung-derived microvesicles. 3. We will determine the component of lung-derived microvesicles (RNA, DNA, protein) that causes epigenetic modification of marrow cells. 4. We will determine if transplantation of marrow cells that have taken up lung-derived microvesicles attenuates radiation and elastase-induced lung injury, thereby improving lung function. 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.
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