Review Article

Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives

Table 5

Surface markers used in EPC identifying.

MoleculesBiological features and relevance in EPC detection

CD34 105- to 120-kD transmembrane cell surface glycoprotein, selectively expressed (within human and murine hematopoietic systems) on stem and progenitor cells, and initially used by Asahara and colleagues for EPC identifying. It is not specific and expressed by mature endothelial cells as well as HSCs [76].

VEGFR2A kinase insert domain receptor (KDR) or Flk-1, or CD309, suggested as further marker for identifying circulating EPC cells. It is expressed mainly on EC cells, and besides EPC cells, in low number, on osteoblasts, pancreatic duct cells, neuronal cells, and lung epithelial cells, even if the biological role in nonendothelial cells remains unclear. VEGFR2 has been shown to be a vital promoter of pathological neovascularization, including cancer and diabetic retinopathy, by making it a potential target in therapy of these diseases. However, neither of these markers is specific for EPCs, either alone or together. Vascular endothelial cells, expressing CD34 and VEGFR2, are not considered to be EPCs [76].

CD133Also known as AC133. It is a marker of immature stem cells, proposed as the third marker for EPCs. Thus, EPCs have been identified as VEGFR-2+/CD133+/CD34+ cells. However, more than 99% of CD34+/KDR+/CD133+ triple positive cells also express CD45, which is a pan leukocyte marker, even if these cells are not able to give rise to EPCs capable of highly differentiating in endothelial cells. As such, CD45 expression on putative EPCs became a bone of contention [76].

CD31Platelet endothelial cell adhesion molecule-1, also defined as PECAM [76].

CD146 S-endo, P1H12 antigen [76].

VWFVon Willebrand factor [76].

eNosEndothelial nitric oxide synthase [76].

E-selectinAlso known as CD62 antigen-like family member E (CD62E). Endothelial-leukocyte adhesion molecule-1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a cell adhesion molecule expressed only on endothelial cells activated by cytokines [76].

C-kitThe protooncogene c-kit is a 145,000 Dalton transmembrane glycoprotein designed as CD117. This receptor tyrosine kinase and its ligand stem cell factor (SDF) mediate pleiotropic functions, including cell survival, differentiation, homing, migration, and proliferation as well as functional activation. It is present on the surface of cells of the mast cell and erythroid lineage as well as on multipotent stem and progenitor cells and megakaryocytes [76].

CXCR4Also known as fusion or leukocyte-derived seven transmembrane-domain receptor (LESTR). It represents the receptor of SDF-1, highly expressed on the surface of CD34 positive cells [76].

UEA-IUlex europaeus lectin [76].