Erythropoietin priming improves the vasculogenic potential of G-CSF mobilized human peripheral blood mononuclear cells. (31st July 2014)

• Record Type: Journal Article
• Authors: Kang, Jeehoon; Yun, Ji-Yeon; Hur, Jin; Kang, Jin-A; Choi, Jae-Il; Ko, Seung Bum; Lee, Jaewon; Kim, Ju-Young; Hwang, In-Chang; Park, Young-Bae; Kim, Hyo-Soo
• Is Part Of: Cardiovascular research. Volume 104:Number 1(2015)
• Page Start: 171
• Page End: 182
• Publication Date: 2014-07-31
• Subjects: Erythropoietin -- G-CSF mobilized peripheral blood mononuclear cells -- Priming -- Vasculogenesis -- Myocardial infarction; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvu180
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: From our previous clinical trials, intracoronary infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells ( mob PBMCs) proved to be effective in improving myocardial contractility and reducing infarct volume in acute myocardial infarction. We tested the effect of priming mob PBMCs with erythropoietin (EPO) to augment its therapeutic efficacy. Methods and results: mob PBMCs were obtained from healthy volunteers after a 3-day subcutaneous injection of G-CSF (10 μg/kg). About 40% of mob PBMCs were EPO receptor (EPOR) (+) and responded to 6 h EPO-priming (10 IU/mL) by increasing the expression of vasculogenic factors (i.e. IL8, IL10, bFGF, PDGF, MMP9) and adhesion molecules (i.e. integrin αV, β1, β2, β8) through the JAK2 and Akt pathway. These responses were also observed in PBMCs from elderly patients with coronary disease. The conditioned media from EPO-primed mob PBMCs contained various cytokines such as IL8, IL10, TNFα, and PDGF, which enhanced the migration and tube formation capability of endothelial cells. EPO-primed mob PBMCs also showed increased adhesion on endothelial cells or fibronectin. Augmented vasculogenic potential of EPO-primed mob PBMCs was confirmed in a Matrigel plug assay, ischaemic hindlimb, and myocardial infarction models of athymic nude mice. There were two action mechanisms: (i) cellular effects confirmed by direct incorporation of human mob PBSCs into mouse vasculature and (ii) indirect humoral effects confirmed by the therapeutic effect of the supernatant of EPO-primed mob PBMCs. Conclusion: Brief ex vivo EPO-priming is a novel method to augment the vasculogenic potential of human mob PBMCs, which would help to achieve better results after intracoronary infusion in myocardial infarction patients.