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TISSUE-SPECIFIC STEM CELLS |
a Department of Blood Group Serology and Transfusion Medicine;
b Department of Internal Medicine, Division of Hematology and Stem Cell Transplantation;
c StemCell Cluster;
d Center for Medical Research, Medical University, Graz, Austria
Key Words. Monocytes • Endothelial progenitor cells • Endothelial cells • Circulating angiogenic cells • Circulating endothelial progenitors • Circulating endothelial cells
Correspondence: Dirk Strunk, M.D., Department of Internal Medicine, Division of Hematology and Stem Cell Transplantation, Medical University, Auenbrugger Pl. 38 A-8036, Graz, Austria. Telephone: 43-316-385-4088; Fax: 43-316-385-4087; e-mail: dirk.strunk{at}klinikum-graz.at
The generation of endothelial progenitor cells (EPCs) from blood monocytes has been propagated as a novel approach in the diagnosis and treatment of cardiovascular diseases. Low-density lipoprotein (LDL) uptake and lectin binding together with endothelial marker expression are commonly used to define these EPCs. Considerable controversy exists regarding their nature, in particular, because myelomonocytic cells share several properties with endothelial cells (ECs). This study was performed to elucidate whether the commonly used endothelial marker determination is sufficient to distinguish supposed EPCs from monocytes. We measured endothelial, hematopoietic, and progenitor cell marker expression of monocytes before and after angiogenic culture by fluorescence microscopy, flow cytometry, and real-time reverse transcription–polymerase chain reaction. The function of primary monocytes and monocyte-derived supposed EPCs was investigated during vascular network formation and EC colony-forming unit (CFU-EC) development. Monocytes cultured for 4 to 6 days under angiogenic conditions lost CD14/CD45 and displayed a commonly accepted EPC phenotype, including LDL uptake and lectin binding, CD31/CD105/CD144 reactivity, and formation of cord-like structures. Strikingly, primary monocytes already expressed most tested endothelial genes and proteins at even higher levels than their supposed EPC progeny. Neither fresh nor cultured monocytes formed vascular networks, but CFU-EC formation was strictly dependent on monocyte presence. LDL uptake, lectin binding, and CD31/CD105/CD144 expression are inherent features of monocytes, making them phenotypically indistinguishable from putative EPCs. Consequently, monocytes and their progeny can phenotypically mimic EPCs in various experimental models.
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