Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice

Abstract

Neonatal hyperoxia impairs vascular and alveolar growth in mice and decreases endothelial progenitor cells. To determine the role of bone marrow-derived cells in restoration of neonatal lung structure after injury, we studied a novel bone marrow myeloid progenitor cell population from Tie2-green fluorescent protein (GFP) transgenic mice (bone marrow-derived angiogenic cells; BMDAC). We hypothesized that treatment with BMDAC would restore normal lung structure in infant mice during recovery from neonatal hyperoxia. Neonatal mice (1-day-old) were exposed to 80% oxygen for 10 days. BMDACs (1 x 10(5)), embryonic endothelial progenitor cells, mouse embryonic fibroblasts (control), or saline were then injected into the pulmonary circulation. At 21 days of age, saline-treated mice had enlarged alveoli, reduced septation, and a reduction in vascular density. In contrast, mice treated with BMDAC 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.

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

“…However, in this study, we found that in the late phase of BPD, a single dose of EPCs administered through the peripheral venous route only increased lung microvessels, with no improvement in alveolar structure as determined by RAC measurements. Compared with the two previous studies (9,10), the reason why mono-EPCs treatment did not result in any improvement in alveolar structure could be due to the selected route of administration.…”

“…The distal lung harbors EPCs (27) that contribute to lung repair, and their depletion in the developing lung is associated with arrested lung development (28,29). Studies showed that provided angiogenic cells could promote alveolar and vascular growth after neonatal hyperoxic exposure, and restore lung structure to normal in infant mice (9). However, in this study, we found that in the late phase of BPD, a single dose of EPCs administered through the peripheral venous route only increased lung microvessels, with no improvement in alveolar structure as determined by RAC measurements.…”

Targeting Inflammation to Prevent Bronchopulmonary Dysplasia: Can New Insights Be Translated Into Therapies?

“…[147][148][149][150] However, administration of conditioned medium from mesenchymal cells can provide similar levels of protection. 149 Furthermore, newborn rats treated with cord blood MSCs display attenuated pulmonary myeloperoxidase, IL-6, TNF␣, and transforming growth factor ␤ expression.…”

Standing on shoulders

“…These progenitor cells seem to play a most important role here, and this may apply to premature infants [7], children with severe lung disease [8] and, perhaps, also adults [9]. Other findings, such as observations that CHSPCs are increased in menstruating females who exhibit a cyclic increase of diffusing capacity [10], and that infusion of angiogenic cells helps to restore alveolar development in a mouse model of bronchopulmonary dysplasia [11], also strongly suggest that angiogenic cells play a role in developing or restoring the pulmonary vasculature and may enhance alveolar formation indirectly.In addition, these observations are in line with older studies. A large interindividual variability in the number of alveoli was recognised decades ago [12][13][14] and one can speculate that this is partly due to biological variation in the numbers and/or ratio of pro-and non-angiogenic CHSPCs.…”