Erythropoietin-mediated activation of functional properties of peripheral blood mononuclear cells in patients with chronic heart failure

Abstract

Stem cell therapy of diseases of the cardiovascular system, such as myocardial infarction is a prospective method for the stimulation of ischemic tissue repair. The main mechanisms of stem and progenitor cells action is a paracrine. The purpose of the study was to assess the effects of erythropoietin on the functional activity of mononuclear cells (MNCs) in patients with chronic heart failure before and after enrichment of peripheral blood with stem and progenitor cells mobilized by granulocyte colony-stimulating factor (G-CSF). 48 patients with coronary heart disease participated in the study. MNCs from the separated blood were isolated by density gradient on Ficoll/verografin. The phenotype of endothelial progenitor cells was investigated using monoclonal antibodies to CD34, CD133, VEGFR2, CD31. The Change of MNCs proliferative potential in response to erythropoietin was evaluated by MTT-test. The cytokine production in conditioned media was studied using ELISA. The effectiveness of mobilized MNC intramyocardial administration was assessed at 6 and 12 months by detection of a change in functional class according to NYHA heart failure, volume ejection fraction of the left ventricle of the heart and a change in myocardial perfusion. We showed that the enrichment of peripheral blood by mobilization of stem and progenitor cells in patients with chronic heart failure led to activation of proliferative potential of MNCs and increased erythropoietin production, a cytokine with pro-angiogenic activity. MNC enriched with stem and progenitor cells being culturing with erythropoietin increased the levels of TNF-α, IL-10, IL-18, IL-8, G-CSF and VEGF, as compared with the basal level of production. Circulating endothelial progenitor cells with the phenotype CD34- /VEGFR2+ have a correlation with the level of erythropoietin production. Secretory erythropoietin level directly correlated with myocardial perfusion, left ventricular ejection fraction and heart failure class at 6 and 12 months follow-up. The findings suggest that erythropoietin improves functional properties of the MNC of patients with heart failure after mobilization with G-CSF.