(446e) Regulating Migration of Bone Marrow Stromal Cells to Injured Bronchial Epithelium

Human bone marrow stromal cells (hMSCs) are a promising source of multipotent progenitors for a broad range of stem cell therapies, including the treatment of lung fibrosis and loss of pulmonary function in cancer patients given the chemotherapy bleomycin. An early step in treatment is hMSCs homing via migration to the site of injury. This study investigates factors regulating migration of hMSCs to bleomycin-exposed bronchial epithelium. The hMSCs employed in this study are multipotent in exhibiting adipogenesis, chondrogenesis and osteogenesis, and the bronchial epithelium is regenerated in vitro at an air-liquid interface. Bleomycin exposure decreases cell density, viability, intracellular adhesion and membrane integrity of the epithelium. Pituitary extract in culture medium strongly suppresses hMSC migration. Conditioning of the medium by the bronchial epithelium results in a 10-fold increase in the number of migrating hMSCs. After the epithelium is exposed to bleomycin, hMSC migration diminishes to the level of the negative control. The inhibitory effect of pituitary extract is observed in different donor preparations of hMSCs that range in colony forming efficiency from 22% to 66%. Migration inhibition factor (MIF), a component of pituitary extract, suppresses migration in a dose-dependent manner. Epithelial culture medium employed in this study contains 85.4 +/- 3.5 ng/ml MIF. At this concentration, rMIF inhibits hMSC migration by 45% to 55%. This is the first report of MIF regulating hMSC migration. MIF, which is released into the bloodstream from the pituitary, may impede hMSC treated of bleomycin-exposed lung. Systemic administration of a MIF inhibitor may improve the efficacy of this stem cell therapy. This work is funded with a grant from the National Science Foundation.