The Long Telling Story of "Endothelial Progenitor Cells": Where Are We at Now?

Abstract

Endothelial progenitor cells (EPCs): The name embodies years of research and clinical expectations, but where are we now? Do these cells really represent the El Dorado of regenerative medicine? Here, past and recent literature about this eclectic, still unknown and therefore fascinating cell population will be discussed. This review will take the reader through a temporal journey that, from the first discovery, will pass through years of research devoted to attempts at their definition and understanding their biology in health and disease, ending with the most recent evidence about their pathobiological role in cardiovascular disease and their recent applications in regenerative medicine.

Keywords: CD34+ hematopoietic stem progenitor cells; angiogenesis; cardiovascular disease; endothelial progenitor cells; regenerative medicine.

Figure 1

Phenotypical and functional differences between “early” and “late” EPCs [12,13,14].

Figure 2

Representative scheme of culture methods developed by different laboratories to obtain “early EPCs”, “late EPCs” (named also ECFCs; endothelial colony-forming cells), and CFU-Hill [12,13,14,15].

Figure 3

Different nomenclature used in the studies to define cells with pro-angiogenic properties. The cells have been divided into two group according to their lineage phenotype.

Figure 4

Schematic representation of CV risk-induced reprogramming of HSPCs at bone marrow level. CV risks promote epigenetic changes in HSPCs that results in abnormal expansion of cells with inflammatory and pro-atherosclerotic features. Specifically, monocytes characterized by more inflammatory phenotypes (e.g., alternative and non-classic monocytes) and generation of circulating progenitors with pro-calcific and pro-fibrotic characteristics [119,120,121,122,123,124].