A new population of bone marrow cells restores lung growth in a model of Bronchopulmonary Dysplasia (BPD)

Abstract

BPD is characterized by impaired lung growth that persists in adulthood. We have shown neonatal hyperoxia reduces bone marrow progenitor cells & causes abnormal lung structure in mice. The role of progenitor cells in lung growth is controversial. We isolated a new population of bone marrow derived angiogenic cells (BMDAC). We hypothesize that BMDACs can home & engraft in the lung, & promote vascular & alveolar growth after neonatal hyperoxic lung injury.Methods: BMDACs from transgenic Tie2‐GFP mice, were cultured on a feeder cell layer, & characterized by FACS. Neonatal mice were exposed to hyperoxia (FiO2=0.8) X 10 days. BMDAC (10^5 cells) were injected into the right ventricle prior to room air recovery X 10 days. Lung morphometry & immunofluorescence was done.Results: BMDAC displayed a phenotype of a myeloid progenitor: CD45+/CD34‐/CD38+/CD11b‐/CXCR4+/Ly6c‐/F4/80+. Hyperoxia impaired lung structure, which persisted in room air recovery in controls. BMDAC treatment improved septation by 78% & vessel density by 134%(p<0.01), equal to room air raised mice. BMDAC engraftment was 12%, & localized to vessel wall & interstitium, in association with Type II cells. BMADCs did not co‐express smooth muscle, endothelial, epithelial or pericyte markers. We conclude BMDACs are a novel cell population that home to sites of injury in the infant lung & stimulate alveolar & vascular growth after neonatal hyperoxia.