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TISSUE-SPECIFIC STEM CELLS |
Departments of aBlood Group Serology and Transfusion Medicine and
bInternal Medicine, Division of Hematology and Stem Cell Transplantation,
cCenter for Medical Research,
dStemCell Cluster, Medical University, Graz, Austria
Key Words. Endothelial progenitor cells • Colony-forming units of endothelial progenitor cells • Vascular regeneration • Regenerative medicine • Immunity
Correspondence: Dirk Strunk, M.D., Department of Internal Medicine, Division of Hematology and StemCell Cluster, Medical University, Auenbrugger Pl. 38, A-8036 Graz, Austria. Telephone: 43-316-385-4088 or -80539; Fax: 43-316-385-4087; e-mail: dirk.strunk{at}klinikum-graz.at
Received January 29, 2007;
accepted for publication March 20, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS March 29, 2007.
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.
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