Abstract
ABSTRACTBackground: Mononuclear cells (MNCs) have well-documented beneficial effects in a wide range of adult pulmonary diseases. The effects of human umbilical cord blood-derived MNCs on neonatal lung injury, highly relevant for potential autologous application in preterm newborns at risk for bronchopulmonary dysplasia (BPD), remain incompletely established. The aim of this study was to determine the long-term morphologic and functional effects of systemically delivered MNCs in a murine model of neonatal lung injury. Materials and Methods: MNCs from cryopreserved cord blood (1 × 106 cells per pup) were given intravenously to newborn mice exposed to 90% O2 from birth; controls received cord blood total nucleated cells (TNCs) or granular cells, or equal volume vehicle buffer (sham controls). In order to avoid immune rejection, we used SCID mice as recipients. Lung mechanics (flexiVent™), engraftment, growth, and alveolarization were evaluated eight weeks postinfusion. Results: Systemic MNC administration to hyperoxia-exposed newborn mice resulted in significant attenuation of methacholine-induced airway hyperreactivity, leading to reduction of central airway resistance to normoxic levels. These bronchial effects were associated with mild improvement of alveolarization, lung compliance, and elastance. TNCs had no effects on alveolar remodeling and were associated with worsened methacholine-induced bronchial hyperreactivity. Granular cell administration resulted in a marked morphologic and functional emphysematous phenotype, associated with high mortality. Pulmonary donor cell engraftment was sporadic in all groups. Conclusions: These results suggest that cord blood MNCs may have a cell type-specific role in therapy of pulmonary conditions characterized by increased airway resistance, such as BPD and asthma. Future studies need to determine the active MNC subtype(s), their mechanisms of action, and optimal purification methods to minimize granular cell contamination.
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