EPCs and pathological angiogenesis: When good cells go bad

• Published in: Microvascular research Vol. 79; no. 3; pp. 207 - 216
• Main Authors: Calzi, Sergio Li, Neu, Matthew B., Shaw, Lynn C., Kielczewski, Jennifer L., Moldovan, Nicanor I., Grant, Maria B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2010
• Subjects: Angiogenesis Inhibitors - therapeutic use; Animals; Cell Differentiation; Cell Lineage; Cell Proliferation; Diabetic retinopathy; Endothelial Cells - drug effects; Endothelial Cells - pathology; Endothelial progenitor cells; Humans; Neoplasms - blood supply; Neoplasms - drug therapy; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - physiopathology; Neovascularization, Pathologic - prevention & control; Neovascularization, Physiologic; Phenotype; Retinal Neovascularization - pathology; Retinal Neovascularization - physiopathology; Stem Cell Niche; Stem cells; Stem Cells - drug effects; Stem Cells - pathology; Diabetic retinopathy; Endothelial progenitor cells; Stem cells
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2010.02.011

Bone-marrow-derived endothelial progenitor cells (EPCs) contribute to angiogenesis-mediated pathological neovascularization, and recent studies have begun to recognize the biological significance of this contribution. This review will discuss the ability of EPCs to contribute to neovascularization in both physiological and pathological conditions. Circulating EPCs were originally identified in 1997 by Asahara as CD34
+ VEGFR2
+ mononuclear cells. These cells differentiated into an endothelial phenotype, expressed endothelial markers, and incorporated into neovessels at sites of ischemia (Asahara et al., 1997). EPCs provide both instructive (release of pro-angiogenic cytokines) and structural (vessel incorporation and stabilization) functions that contribute to the initiation of neo-angiogenesis. EPC populations can be characterized based on surface markers of freshly isolated cells, or they can be described by their
in vitro characteristics once placed in culture. However, a major stumbling block to progress in the field has been the lack of consensus among investigators as to the optimal characterization of EPCs. This review intends to address the role of both EPC classes and evaluate how they interact in the setting of pathological angiogenesis. Since the EPCs may be responsible for turning on the “angiogenic switch,” strategies have been employed to keep this switch in the “off” position for diseases like cancer, retinopathy, and wet AMD. The expectation is that EPCs will evolve into clinically useful prognostic and predictive tools in cancer and in ocular diseases associated with pathological neovascularization and that targeting this cell type is a key to successful management of patients suffering from diseases associated with pathological neovascularization.