Erythropoietin improves the efficiency of endothelial progenitor cell therapy after myocardial infarction in mice: effects on transplanted cell survival and autologous endothelial progenitor cell mobilization.

Abstract

BACKGROUND:

Endothelial progenitor cells (EPCs) participate in vascular repair and angiogenesis. Thus, EPC transplantation into ischemic myocardium might improve cardiac function; however, the vast majority of cells die within a short period. The present study was designed to investigate whether exogenous erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and enhance the efficiency of EPC-based cell therapy.

METHODS:

Myocardial infarction was induced in wild-type mice by ligating the left anterior descending coronary artery. Enhanced green fluorescent protein-EPCs with or without EPO were transplanted into peri-infarct myocardium. Enhanced green fluorescent protein-EPCs were detected 7 and 28 d after surgery. The amount of circulating EPCs was analyzed 3 and 28 d after surgery. The stromal cell-derived factor-1α and vascular endothelial growth factor concentrations, microvessel density, apoptosis, fibrosis in the peri-infarct myocardium, and cardiac function were compared among the groups.

RESULTS:

More enhanced green fluorescent protein-EPCs were found in the hearts treated with EPC + EPO than in those treated with EPC alone. The circulating EPC level was markedly elevated after EPC + EPO treatment compared with EPC application alone. Stromal cell-derived factor-1α and vascular endothelial growth factor were increased accordingly, along with increased microvessel density, decreased apoptosis, and reduced fibrosis in the peri-infarct myocardium. Left ventricular fractional shortening was greater and the interventricular septum was thicker after EPC + EPO treatment compared with EPC treatment alone.

CONCLUSIONS:

EPO improved the efficiency of EPC therapy in mice with myocardial infarction. This effect was associated with enhanced transplanted EPC survival and autologous EPC mobilization.

• Authors: Yan Cheng, Ruoyu Hu, Lei Lv, Lin Ling, Shisen Jiang
• Journal: The Journal of surgical research (J Surg Res) Vol. 176 Issue 1 Pg. e47-55 (Jul 2012) ISSN: 1095-8673 [Electronic] United States
• PMID: 22595018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Chemokine CXCL12
• Vascular Endothelial Growth Factor A
• Erythropoietin
• Green Fluorescent Proteins

Topics

• Animals
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Cell- and Tissue-Based Therapy
• Chemokine CXCL12 (metabolism)
• Electrocardiography
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Erythropoietin (pharmacology)
• Green Fluorescent Proteins (genetics)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Models, Animal
• Myocardial Infarction (metabolism, pathology, therapy)
• Neovascularization, Physiologic (drug effects)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (metabolism)