Abstract
BackgroundPostnatal 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.ResultsIn 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.ConclusionThe 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.
Highlights
Postnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels
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
Mouse lungs contain Endothelial cells (ECs) with high proliferation capacity Using adult mouse lung for magneto-bead selection of CD31+ endothelial cells, we discovered that the lung contains endothelial cells, which have a high proliferative capacity
Summary
Postnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, be classified into circulating and resident progenitor cells. In the developing embryo blood vessels and later lymphatic vessels are formed via an initial process of vasculogenesis This is followed by sprouting and intussusceptive growth of the vessels, termed angiogenesis for blood vessels and lymphangiogenesis for lymph vessels. Endothelial cells (ECs) are specified according to the circulatory system (blood versus lymph) and to the vessel type (vein, artery, capillary) to which they belong [1]. At least some microvascular ECs and ECs in specific niches possess high endogenous proliferation capacities in vivo, as well as high angiogenic potential as part of their physiological role
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