Therapeutic Potential of Endothelial Progenitor Cells in Pulmonary Diseases

Am J Respir Cell Mol Biol. 2021 Nov;65(5):473-488. doi: 10.1165/rcmb.2021-0152TR.


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.

Keywords: alveolar capillary dysplasia with misalignment of pulmonary veins; bronchopulmonary dysplasia; directed differentiation of embryonic stem cells and induced pluripotent stem cells into endothelial progenitor cells; endothelial progenitor cells; pulmonary disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bronchopulmonary Dysplasia / pathology*
  • Bronchopulmonary Dysplasia / therapy
  • Cell Differentiation
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / physiology*
  • Endothelial Progenitor Cells / transplantation
  • Gene Expression Regulation
  • Humans
  • Induced Pluripotent Stem Cells
  • Infant, Premature
  • Lung / blood supply
  • Lung / embryology
  • Lung / metabolism
  • Lung Diseases / pathology
  • Lung Diseases / therapy*
  • Persistent Fetal Circulation Syndrome / pathology*
  • Persistent Fetal Circulation Syndrome / therapy