Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity

Diego F. Alvarez, Lan Huang, Judy A. King, M. Khair Elzarrad, Mervin C. Yoder, Troy Stevens

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Endothelial progenitor cells (EPCs) have been isolated postnatally from bone marrow, blood, and both the intima and adventitia of conduit vessels. However, it is unknown whether EPCs can be isolated from the lung microcirculation. Thus we sought to determine whether the microvasculature possesses EPCs capable of de novo vasculogenesis. Rat pulmonary artery (PAEC) and microvascular (PMVEC) endothelial cells were isolated and selected by using a single-cell clonogenic assay. Whereas the majority of PAECs (∼60%) were fully differentiated, the majority of PMVECs (∼75%) divided, with ∼50% of the single cells giving rise to large colonies (>2,000 cells/colony). These highly proliferative cells exhibited the capacity to reconstitute the entire proliferative hierarchy of PMVECs, unveiling the existence of resident microvascular endothelial progenitor cells (RMEPCs). RMEPCs expressed endothelial cell markers (CD31, CD144, endothelial nitric oxide synthase, and von Willenbrand factor) and progenitor cell antigens (CD34 and CD309) but did not express the leukocyte marker CD45. Consistent with their origin, RMEPCs interacted with Griffonia simplicifolia and displayed restrictive barrier properties. In vitro and in vivo Matrigel assays revealed that RMEPCs possess vasculogenic capacity, forming ultrastructurally normal de novo vessels. Thus the pulmonary microcirculation is enriched with EPCs that display vasculogenic competence while maintaining functional endothelial microvascular specificity.

Original languageEnglish (US)
Pages (from-to)L419-L430
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume294
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Endothelial progenitor cells
  • Pulmonary circulation
  • Vasculogenesis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

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