Endothelial progenitor cells: identity defined?

Abstract

In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133+ cells or CD45+ haematopoietic cells.

Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling

“…The EPCs phenotypes population, that is, those expressing at least one immaturity/stemness marker such as CD34 or CD133 and at least one endothelial antigen (usually KDR), likely have different biological meaning, as the exact surface phenotype of EPCs is not known and no single antigenic combination can unequivocally identify EPCs. 8,46,47 Therefore, clinical correlation data such as provided by our study are useful to attribute more biological relevance to one putative EPC phenotype vs. the others. For example, one could speculate that CD34+KDR+ cell phenotype may correlate with pathological vascular damage and increased CV risk, 48 while CD133+KDR+ and CD34+CD133+KDR+ are likely related to oxidative status and endothelial function as suggested by their status in BS/GS that is, increased CD133+KDR+ and CD34+CD133+KDR+ and unchanged CD34+KDR+, which fits with the biochemical, molecular and functional picture of good endothelial status reported in these patients.…”

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

“…However, present studies point to a limited incorporation of bone marrow-derived cells into the endothelium of tumours (Peters et al, 2005). Many recent studies and reviews discuss the properties of pro-angiogenic cell populations or 'circulating angiogenic cells' in depth (Case et al, 2007;Timmermans et al, 2007Timmermans et al, , 2008Hirschi et al, 2008;Gao et al, 2009;Yoder and Ingram, 2009). A specific role of CD133 þ /HPCs has been suggested in pulmonary vascular remodelling in patients with obstructive pulmonary disease (Asosingh et al, 2008) or idiopathic pulmonary arterial hypertension (Diez et al, 2007).…”

“…In addition, the possibility to monitor circulating endothelial progenitor cells (CEPs) has been proposed as an attractive biomarker for anti-angiogenic agents after the seminal identification of circulating progenitors, which could grow out to highly proliferative endothelial outgrowth cells (EOCs) (Ingram et al, 2005;Shaked et al, 2006). Although originally CEPs were discriminated from mature CECs mainly by the presence or absence of CD133 progenitor markers, more recent data have cast serious doubts on this premise (Timmermans et al, 2008;Yoder and Ingram, 2009). …”

Endothelial Outgrowth Cells: Function and Performance in Vascular Grafts

“…25 The features of EOCs that make them well suited for tissue engineering include (1) robust proliferation rate, (2) high expansion potential, and (3) simple sourcing via venipuncture. 16,[25][26][27] The high proliferation rate and expansion potential of EOCs allows very few colonies to be quickly expanded to the high cell number required for tissue engineering applications, and venipuncture is considerably less invasive than harvesting ECs from excised tissue.…”

“…14 Since this discovery, research has sought to characterize the various subtypes of cells that differentiate from circulating progenitors, [15][16][17][18] develop protocols for EPC characterization and quantification, [19][20][21][22] and establish the clinical relevance of EPC count. 23,24 Among the phenotypically and functionally diverse progeny of EPCs, a population termed endothelial outgrowth cells (EOCs; also known as late outgrowth, blood outgrowth endothelial, or endothelial colonyforming cells) are particularly promising for vascular tissue engineering applications.…”