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Tissue-Specific Stem Cells |
1 Department of Blood Group Serology and Transfusion Medicine, Medical University, Graz, Austria; StemCell Cluster, Medical University, Graz, Austria
2 Department of Blood Group Serology and Transfusion Medicine, Medical University, Graz, Austria; Department of Internal Medicine, Division of Hematology and Stem Cell Transplantation, Medical University, Graz, Austria; StemCell Cluster, Medical University, Graz, Austria
3 Department of Internal Medicine, Division of Hematology and Stem Cell Transplantation, Medical University, Graz, Austria; StemCell Cluster, Medical University, Graz, Austria
4 Department of Blood Group Serology and Transfusion Medicine, Medical University, Graz, Austria
5 Department of Internal Medicine, Division of Hematology and Stem Cell Transplantation, Medical University, Graz, Austria
6 Center for Medical Research, Medical University, Graz, Austria
* To whom correspondence should be addressed. E-mail: dirk.strunk{at}klinikum-graz.at.
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Abstract |
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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 NK 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 towards models that include a role for immune cells in vascular regeneration.
Key Words. Endothelial Progenitor Cells, EPC, CFU-EC, Vascular Regeneration, Regenerative Medicine, Immunity
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