P4: BM-DERIVED STEM CELLS HOMING AND LUNG CELL PRODUCTION IN INJURED LUNG

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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. The specific aims of this project are: 1) To evaluate the variables that influence lung cell production from marrow cells; 2) To evaluate marrow and lung cells response to injury and factors influencing the homing of marrow cells to injured lung; and 3) Apply optimal homing and lung cell production conditions, as outlined in aims 1 and 2, to marrow transplantation in two separate mouse-injury models: bleomycin-induced pulmonary fibrosis and elastase-induced emphysema. We and others have demonstrated that marrow cells are capable of participating in the production of various lung cells in the setting of lung injury. Furthermore, others have demonstrated histological and functional improvement of the injured lung after marrow cell infusion in specific injury models (decreased lung collagen content in bleomycin-injured mice, decreased pulmonary hypertension in monocrotaline-injured rats). Our hope is that marrow cells possess sufficient reparative properties to provide a novel therapeutic option for pulmonary diseases for which there are few effective treatments.