Compromised alveolar development and pulmonary
vascular remodeling are hallmarks of pediatric
lung diseases such as
bronchopulmonary dysplasia (BPD) and
alveolar capillary dysplasia with misalignment of pulmonary veins (
ACDMPV). Although advances in
surfactant therapy,
corticosteroids, and antiinflammatory drugs have improved clinical management of preterm infants, those who suffer with severe vascular complications still lack viable treatment options. Paucity of the alveolar capillary network in
ACDMPV causes respiratory distress and leads to mortality in a vast majority of infants with
ACDMPV. The discovery of endothelial progenitor cells (EPCs) in 1997 brought forth the paradigm of postnatal vasculogenesis and hope for promoting vascularization in fragile patient populations, such as those with BPD and
ACDMPV. The identification of diverse
EPC populations, both hematopoietic and nonhematopoietic in origin, provided a need to identify progenitor cell-selective markers that are linked to progenitor properties needed to develop cell-based
therapies. Focusing on the future potential of EPCs for regenerative medicine, this review will discuss various aspects of
EPC biology, beginning with the identification of hematopoietic, nonhematopoietic, and tissue-resident
EPC populations. We will review knowledge related to cell surface markers, signature gene expression, and key transcriptional regulators and will explore the translational potential of EPCs for cell-based
therapy for BPD and
ACDMPV. The ability to produce pulmonary EPCs from patient-derived induced pluripotent stem cells in vitro holds promise for restoring vascular growth and function in the lungs of patients with pediatric pulmonary disorders.