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Erythropoietin Priming Improves the Vasculogenic Potential of G-CSF mobilized Human Peripheral Blood Mononuclear Cells.
MedLine Citation:
PMID:  25082847     Owner:  NLM     Status:  Publisher    
AIM: 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, ischemic hindlimb and myocardial infarction models of athymic nude mice. There were two action mechanisms: (1) cellular effects confirmed by direct incorporation of human (mob)PBSCs into mouse vasculature; and (2) indirect humoral effects confirmed by the therapeutic effect of the supernatant of EPO-primed (mob)PBMCs.
CONCLUSIONS: 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.
Jeehoon Kang; Ji-Yeon Yun; Jin Hur; Jin-A Kang; Jae-Il Choi; Seung Bum Ko; Jaewon Lee; Ju-Young Kim; In-Chang Hwang; Young-Bae Park; Hyo-Soo Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-31
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email:
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