Abstract
The human HEPC-CB.1 cell line with many characteristics of endothelial progenitor cells (EPC) was tested for its proangiogenic properties as a potentially therapeutic compound. HEPC-CB.1 cells’ potential to differentiate into endothelial cells was revealed after treating the cells with a mixture of ATRA, cAMP and VEGF, as shown by the reduced expression levels of CD133, CD271 and CD90 antigens, augmentation of CD146 and CD31, and a decrease in cell clonogenicity. The cooperation of HEPC-CB.1 with the endothelial cell line HSkMEC.2 resulted in the formation of a common network. Tube formation was significantly more effective when resulting from HEPC-CB.1 and HSkMEC.2 cell co-culture as compared to a monoculture of each cell line. The exocrine mechanism of HEPC-CB.1 and HSkMEC.2 cross talk by secreted factors was evidenced using the HEPC-CB.1 supernatant to increase the efficacy of HSkMEC.2 tube formation. The proangiogenic factors produced by HEPC-CB.1 were identified using cytokine antibody array. Out of 120 examined factors, the HEPC-CB.1 cell line produced 63, some with known angiogenic activity. As in vivo the angiogenic process occurs at low oxygen tension, it was observed that in hypoxia, the production of defined factors was augmented. The presented results demonstrate that HEPC-CB.1 cells are able to both cooperate and integrate in a newly formed network and produce factors that help the network formation. The results suggest that HEPC-CB.1 cells are indeed endothelial progenitors and may prove to be an effective tool in regenerative medicine.
Highlights
22 years have passed since the discovery of endothelial progenitor cells (EPC) [1], they have not yet been clearly defined
Because the phenotype of the HEPC-CB.1 cells indicates that they correspond to real EPC, we examined whether they retain the ability to differentiate towards mature endothelium
Since we have shown that cell-free supernatants from HEPC-CB.1 cells exert a proangiogenic effect on the nets formed by HSKMEC.2 cells, an important question arises: what specific pro-angiogenic factors are secreted by these cells? This question seems important if the real EPC cells at this early stage of differentiation are considered as a hypothetical tool in regenerative medicine
Summary
22 years have passed since the discovery of endothelial progenitor cells (EPC) [1], they have not yet been clearly defined. The definition of EPC cells includes both myeloid angiogenic cells of hematopoietic. Each of them has a different origin and—as many researchers emphasize—functional features. In the Timmermans review about 20 phenotypes of human EPC cells used by different researchers were described [4, 5]. Different combinations of CD34, CD133, CD31, VE-cadherin, CD146, and VEGFR2 markers were applied to discriminate EPC from other cells as to date no EPC specific marker has been found. The lack of a specific marker of EPC cells and very low number of these cells in the organs and circulation cause many problems in identification, isolation and especially application. Recently have there appeared works attempting to introduce the correct EPC nomenclature [6]
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