Immune Cells Mimic Endothelial Progenitor Colonies.

Abstract

Colony-forming units of endothelial progenitor cells (“CFU-EC”) have been introduced as a powerful biological marker for vascular function and cumulative cardiovascular risk. The precise mechanisms underlying the colony formation and their cellular composition are unclear. We hypothesized that “CFU-EC” display an immune cell function distinct from circulating endothelial progenitors. We performed detailed subtractive “CFU-EC” analyses in blood samples from 18 healthy volunteers. The impact of various blood cell types and kinetics of protein and gene expression were studied by cell sorting, flow cytometry, quantitative RT-PCR and full genome microarray analyses. “CFU-EC”-derived soluble factors were determined in multiplex cytokine measurements and tested during endothelial network formation. “CFU-EC” contained more than 99% CD45+ nucleated hematopoietic cells mainly comprising T cells and monocytes admixed with B and NK cells. Interestingly, purified T-cells plus monocytes formed “CFU-EC” clusters. The complete lack of colony formation after depletion of T cells or monocytes was contrasted by effective “CFU-EC” formation after depletion of CD34+ progenitors. Microarray analyses revealed an activation of immune function-related biological processes without changes in pathways assigned to angiogenesis. Soluble factors derived from “CFU-EC” cultures supported vascular regeneration in vitro. Unravelling “CFU-EC” formation as a result of a functional crosstalk between T cells and monocytes shifts expectations on vascular regenerative medicine. The data support a switch from a sole view on circulating endothelial progenitors towards models that favor the contribution of immune cells to vascular regeneration.