Endothelial Progenitors: A Consensus Statement on Nomenclature

Abstract

Endothelial progenitor cell (EPC) nomenclature remains ambiguous and there is a general lack of concordance in the stem cell field with many distinct cell subtypes continually grouped under the term "EPC." It would be highly advantageous to agree on standards to confirm an endothelial progenitor phenotype and this should include detailed immunophenotyping, potency assays, and clear separation from hematopoietic angiogenic cells which are not endothelial progenitors. In this review, we seek to discourage the indiscriminate use of "EPCs," and instead propose precise terminology based on defining cellular phenotype and function. Endothelial colony forming cells and myeloid angiogenic cells are examples of two distinct and well-defined cell types that have been considered EPCs because they both promote vascular repair, albeit by completely different mechanisms of action. It is acknowledged that scientific nomenclature should be a dynamic process driven by technological and conceptual advances; ergo the ongoing "EPC" nomenclature ought not to be permanent and should become more precise in the light of strong scientific evidence. This is especially important as these cells become recognized for their role in vascular repair in health and disease and, in some cases, progress toward use in cell therapy. Stem Cells Translational Medicine 2017;6:1316-1320.

Keywords: Angiogenesis; Cellular therapy; Endothelial cell; Progenitor cells.

Figure 1

Methodology used to study human endothelial progenitors. Enumeration of EPCs circulating in blood is performed using flow cytometry. Cell culture technology consistently allows the isolation of well‐defined cell populations with vasoreparative properties such as ECFCs and MACs. ECFCs are fully committed to the endothelial lineage while MACs exhibit a phenotype similar to M2 macrophages. ≠ indicates that ECFCs and MACs represent highly distinct cell populations evidenced by their immunophenotype and pro‐angiogenic mechanism of action. Abbreviations: ECFCs, endothelial colony forming cells; EPC, endothelial progenitor cell; MACs, myeloid angiogenic cells; VEGFR2, vascular endothelial growth factor receptor 2.

Figure 2

Cell types studied for their pro‐angiogenic properties. Complex nomenclature can be divided into two distinct groups according to phenotypic lineage: hematopoietic and endothelial. Table provides minimal criteria to define MACs and ECFCs based on immunophenotype, including negative markers for purity; and function, assessed as a potency assay. Abbreviations: BOECs, blood outgrowth endothelial cells; CACs, circulating angiogenic cells'; CFU, colony forming unit; ECFCs, endothelial colony forming cells; OECs, endothelial outgrowth cells; EPC, endothelial progenitor cell; MACs, myeloid angiogenic cells; PACs, pro‐angiogenic hematopoietic cells.