Existence, Functional Impairment, and Lung Repair Potential of Endothelial Colony-Forming Cells in Oxygen-Induced Arrested Alveolar Growth

Background

Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth.

In Conclusion

We show for the first time that ECFCs exist in the distal vasculature of the developing mammalian lung, and their functional capacity is impaired in oxygen-induced lung damage. We also show that therapeutic supplementation with human umbilical cord blood–derived ECFCs is feasible, efficacious, and apparently safe in this experimental O₂-induced model of BPD in neonatal mice.