The ends of the bones were cut off, and the marrow was flushed with saline. had complete restoration of lung structure that was indistinguishable from room air controls. BMDAC comprised 12% of distal lung cells localized to pulmonary vessels or alveolar type II (AT2) cells and persist (8.8%) for 8 wk postinjection. Coculture of AT2 cells or lung endothelial cells (luEC) with BMDAC augmented AT2 and luEC cell growth in vitro. We conclude that treatment with BMDAC after neonatal hyperoxia restores lung structure in this model of bronchopulmonary dysplasia. Keywords:bronchopulmonary dysplasia, stem cell, oxygen, alveolar type 2 cell, endothelial cell premature birth and the treatmentof respiratory distress syndrome with oxygen and mechanical ventilation leads to the development of MNS chronic lung MNS disease known as bronchopulmonary dysplasia (BPD; Ref.45). BPD is usually characterized by persistent abnormalities of lung structure due to dysmorphic vascular growth and impaired alveolarization (13,32). Structural lung abnormalities in infants with BPD include a reduction of lung surface area, resulting in abnormal gas exchange, exercise intolerance, and pulmonary hypertension (2,13,28,31,51,52). Oxygen toxicity in the developing lung contributes to the pathogenesis of BPD, but mechanisms by which hyperoxia induces lung injury and impairs lung repair are unclear (62,63,65). Previous studies MNS have shown that postnatal lung injury during the alveolar stage of lung development disrupts both alveolar and vascular growth (44,48,49,53,64). In addition, disruption of vascular growth during the alveolar stage is sufficient to impair septation, leading to marked simplification of the distal lung structure (30,40). Neonatal hyperoxia exposure provides a useful model to study BPD Sox2 (20,66). Studies using extreme hyperoxia (>95% O2) have demonstrated a striking inhibition of distal lung growth that persists during infancy and into adulthood, as evidenced by increased distal air space size with reduced septation and decreased vascular density (18,19,38,41,48,49,62,64). Moderate hyperoxia (6065% O2) has also been shown to inhibit lung vascular and alveolar growth in neonatal rodents (8,11,15,23). These changes in lung structure closely mimic the histology of altered lung architecture observed in human infants with BPD (13,28,31,32,51,52), thereby providing a useful experimental model for studying BPD. Hyperoxia may impair lung growth by multiple mechanisms, including effects on circulating and endogenous progenitor cell populations. Circulating bone marrow-derived endothelial progenitor cells (EPC) play a role in the repair of several organs after vascular injury by promoting neovascularization in the heart (4,34), brain (69), and ischemic hindlimb (5,33) of adult animals. We have previously observed that neonatal mice demonstrate emphysematous changes in lung structure after exposure to moderate levels of hyperoxia, whereas the same level of hyperoxia does not affect lung structure of adult mice (8). Levels of EPC were reduced in the blood, bone marrow, and lungs of infant mice exposed to hyperoxia but increased in adult mice exposed to hyperoxia (8). Furthermore, in this model, suppression of the bone marrow of the adult mouse by irradiation confers a susceptibility to hyperoxia-induced alterations of lung structure, thus suggesting a role for a bone marrow-derived cell population in the maintenance of lung structure in the adult exposed to hyperoxia (8). Bone marrow-derived mesenchymal stem cell (MSC) treatment has been suggested as a therapy for ischemic heart disease (29,61) and as a potential therapy for stroke (54). These studies suggest that the targeting of increasing levels of circulating bone marrow-derived progenitors may be a therapeutic strategy for the restoration of various organs after injury. Local endogenous populations of stem or progenitor cells have been identified in the different regions of the respiratory tract (27). These cells include the basal epithelial cells in the trachea and bronchi (26), CC10-positive Clara cells in.