title: Immune cells mimic the morphology of endothelial progenitor colonies in vitro.
abstract: Endothelial progenitor cells (EPC) are considered powerful biologic markers for vascular function and cardiovascular risk, predicting events and death from cardiovascular causes. Colony-forming units of endothelial progenitor cells (CFU-EC) are used to quantify EPC circulating in human peripheral blood. The mechanisms underlying colony formation and the nature of the contributing cells are not clear. We performed subtractive CFU-EC analyses to determine the impact of various blood cell types and kinetics of protein and gene expression during colony formation. We found that CFU-EC mainly comprise T cells and monocytes admixed with B cells and natural killer cells. The combination of purified T cells and monocytes formed CFU-EC structures. The lack of colonies after depletion or functional ablation of T cells or monocytes was contrasted with effective CFU-EC formation in the absence of CD34+ cells. Microarray analyses revealed activation of immune function-related biological processes without changes in angiogenesis-related processes during colony formation. In concordance with a regenerative function, soluble factors derived from CFU-EC cultures supported vascular network formation in vitro. Recognizing CFU-EC formation as the result of a functional cross between T cells and monocytes shifts expectations of vascular regenerative medicine. Our data support the move from a view of circulating EPC toward models that include a role for immune cells in vascular regeneration. Disclosure of potential conflicts of interest is found at the end of this article.
authors: Department of Blood Group Serology and Transfusion Medicine, Division of Hematology and StemCell Cluster, Medical University, Auenbrugger Pl. 38, A-8036 Graz, Austria.
authors: Eva
authors: E
authors: Rohde
authors: Christina
authors: C
authors: Bartmann
authors: Katharina
authors: K
authors: Schallmoser
authors: Andreas
authors: A
authors: Reinisch
authors: Gerhard
authors: G
authors: Lanzer
authors: Werner
authors: W
authors: Linkesch
authors: Christian
authors: C
authors: Guelly
authors: Dirk
authors: D
authors: Strunk
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology*
chemical_list: D018952:Antigens, CD34