• Olena A Kolesnichenko, Jeffrey A Whitsett, Tanya V Kalin, and Vladimir V Kalinichenko.
• Cincinnati Children's Hospital Medical Center, 2518, Cincinnati, Ohio, United States.
• Am. J. Respir. Cell Mol. Biol. 2021 Jul 22.

AbstractCompromised 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 anti-inflammatory drugs have improved clinical management of preterm infants, still those who suffer with severe vascular complications lack viable treatment options. Paucity of the alveolar capillary network in ACDMPV causes respiratory distress and leads to mortality in a vast majority of ACDMPV infants. 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 which are linked to progenitor properties needed to develop cell-based therapies. Focusing to 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, 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 (iPSCs) in vitro, holds promise for restoring vascular growth and function in the lungs of patients with pediatric pulmonary disorders.

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