Endothelial progenitor cells for cardiovascular regeneration

Abstract

Endothelial progenitor cells (EPCs) are peripheral blood mononuclear cells that can differentiate into mature endothelial cells. Adult EPCs were first discovered in human peripheral blood in 1997. Since then, the potency of EPCs for cardiovascular regeneration has been demonstrated in several preclinical studies; and investigators are beginning to evaluate the therapeutic utility of EPCs in early-phase clinical trials. This review summarizes the progression of basic, preclinical, and clinical research into the potential use of EPC therapy for cardiovascular regeneration.

Figure 1

Mechanism of endothelial progenitor cell (EPC)-mediated postnatal neovascularization. Circulating EPCs mobilized from bone marrow are recruited into the foci of neovascularization and contribute to new blood vessel formation. The intrinsic EPC activity can be augmented by certain cytokines, growth factors, and pharmaceutical agents. G-CSF indicates granulocyte colony stimulating factor; GM-CSF, granulocyte macrophage colony stimulating factor; VEGF, vascular endothelial growth factor; SDF-1, stromal cell-derived factor-1.

Figure 2

Representative histological assessments 3 days after intramyocardial injection of CD34+ cells or total mononuclear cells (MNCs). Experiments were performed in nude rats with acute myocardial infarction. Animals in both treatment groups were administered the same number of CD34+ cells. (a) Hematoxylin-eosin staining of the infarct area revealed massive hemorrhagic infarction (arrows) in rats administered total MNCs. (b) Immunostaining for human-specific CD45 to identify hematopoietic/inflammatory cells (arrows) in the infarcted myocardium. Human CD45+ cells were abundant in the total MNC treatment group, but not in the purified CD34+ cell treatment group.