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Am J Physiol Lung Cell Mol Physiol (December 7, 2007). doi:10.1152/ajplung.00314.2007
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Submitted on August 6, 2007
Accepted on November 29, 2007

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

Diego F. Alvarez1, Lan Huang2, Judy A. C. King1, M. Khair ElZarrad3, Mervin C. Yoder2, and Troy Stevens4*

1 Center for Lung Biology, University of South Alabama, Mobile, Alabama, United States
2 Pediatrics, University of Indiana, Indianapolis, Indiana, United States
3 Pharmacology, University of South Alabama, Mobile, Alabama, United States
4 Center for Lung Biology, Department of Pharmacology, University of South Alabama College of Medicine, Mobile, Alabama, United States

* To whom correspondence should be addressed. E-mail: tstevens{at}jaguar1.usouthal.edu.

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. While 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, eNOS and vWf) 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 endothelial progenitor cells that display vasculogenic competence, while maintaining functional endothelial microvascular specificity.




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