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Open Access Highly Accessed Research article

Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

Judith Schniedermann1, Moritz Rennecke1, Kerstin Buttler2, Georg Richter1, Anna-Maria Städtler1, Susanne Norgall1, Muhammad Badar1, Bernhard Barleon3, Tobias May1, Jörg Wilting2 and Herbert A Weich1*

Author Affiliations

1 Helmholtz Centre for Infection Research, Division Molecular Biotechnology, Department of Gene Regulation, Braunschweig, Germany

2 Department of Anatomy and Cell Biology, Georg-August-University, Goettingen, Germany

3 RELIATech Research Lab, Receptor Ligand Technologies GmbH, Wolfenbuettel, Germany

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BMC Cell Biology 2010, 11:50  doi:10.1186/1471-2121-11-50

Published: 1 July 2010

Abstract

Background

Postnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated.

Results

In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels.

Mouse lung microvascular endothelial cells (MLMVECs) were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony). These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs) in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels.

Conclusion

The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.