title: Isolation and characterization of circulating lymphatic endothelial colony forming cells.
abstract: BACKGROUND
  The identification of circulating endothelial progenitor cells has led to speculation regarding their origin as well as their contribution to neovascular development. Two distinct types of endothelium make up the blood and lymphatic vessel system. However, it has yet to be determined whether there are distinct lymphatic-specific circulating endothelial progenitor cells.
  
  
  OBJECTIVE
  This study aims to isolate and characterize the cellular properties and global gene expression of lymphatic-specific endothelial progenitor cells.
  
  
  RESULTS
  We isolated circulating endothelial colony forming cells (ECFCs) from whole peripheral blood. These cells are endothelial in nature, as defined by their expression of endothelial markers and their ability to undergo capillary morphogenesis in three-dimensional culture. A subset of isolated colonies express markers of lymphatic endothelium, including VEGFR-3 and Prox-1, with low levels of VEGFR-1, a blood endothelial marker, while the bulk of the isolated cells express high VEGFR-1 levels with low VEGFR-3 and Prox-1 expression. The different isolates have differential responses to VEGF-C, a lymphatic endothelial specific cytokine, strongly suggesting that there are lymphatic specific and blood specific ECFCs. Global analysis of gene expression revealed key differences in the regulation of pathways involved in cellular differentiation between blood and lymphatic-specific ECFCs.
  
  
  CONCLUSIONS
  These data indicate that there are two distinguishable circulating ECFC types, blood and lymphatic, which are likely to have discrete functions during neovascularization.
authors.affiliation: University of Washington, Department of Microbiology, Seattle, WA 98195 USA.
authors.forename: Terri A
authors.initials: TA
authors.lastname: DiMaio
authors.affiliation: University of Washington, Department of Microbiology, Seattle, WA 98195 USA.
authors.forename: Breanna L
authors.initials: BL
authors.lastname: Wentz
authors.affiliation: University of Washington, Department of Microbiology, Seattle, WA 98195 USA. Electronic address: lagunoff@uw.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Lagunoff
mesh_terms: D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D042582:Vascular Endothelial Growth Factor C; D000098551:Prospero-Related Homeobox 1 Protein; C581309:FLT4 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Endothelial progenitor; Lymphatic endothelial progenitor; Prox-1; VEGFR-3