Embryonic cardiomyocyte, but not autologous stem cell transplantation, restricts infarct expansion, enhances ventricular function, and improves long-term survival.

Abstract

AIMS:

Controversy exists in regard to the beneficial effects of transplanting cardiac or somatic progenitor cells upon myocardial injury. We have therefore investigated the functional short- and long-term consequences after intramyocardial transplantation of these cell types in a murine lesion model.

METHODS AND RESULTS:

Myocardial infarction (MI) was induced in mice (n = 75), followed by the intramyocardial injection of 1-2×10(5) luciferase- and GFP-expressing embryonic cardiomyocytes (eCMs), skeletal myoblasts (SMs), mesenchymal stem cells (MSCs) or medium into the infarct. Non-treated healthy mice (n = 6) served as controls. Bioluminescence and fluorescence imaging confirmed the engraftment and survival of the cells up to seven weeks postoperatively. After two weeks MRI was performed, which showed that infarct volume was significantly decreased by eCMs only (14.8±2.2% MI+eCM vs. 26.7±1.6% MI). Left ventricular dilation was significantly decreased by transplantation of any cell type, but most efficiently by eCMs. Moreover, eCM treatment increased the ejection fraction and cardiac output significantly to 33.4±2.2% and 22.3±1.2 ml/min. In addition, this cell type exclusively and significantly increased the end-systolic wall thickness in the infarct center and borders and raised the wall thickening in the infarct borders. Repetitive echocardiography examinations at later time points confirmed that these beneficial effects were accompanied by better survival rates.

CONCLUSION:

Cellular cardiomyoplasty employing contractile and electrically coupling embryonic cardiomyocytes (eCMs) into ischemic myocardium provoked significantly smaller infarcts with less adverse remodeling and improved cardiac function and long-term survival compared to transplantation of somatic cells (SMs and MSCs), thereby proving that a cardiomyocyte phenotype is important to restore myocardial function.

• Authors: Leonie E Paulis, Alexandra M Klein, Alexander Ghanem, Tessa Geelen, Bram F Coolen, Martin Breitbach, Katrin Zimmermann, Klaas Nicolay, Bernd K Fleischmann, Wilhelm Roell, Gustav J Strijkers
• Journal: PloS one (PLoS One) Vol. 8 Issue 4 Pg. e61510 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23585908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Luciferases

Topics

• Animals
• Cardiac Output (physiology)
• Cardiomyoplasty (methods)
• Embryo, Mammalian
• Genes, Reporter
• Injections, Intramuscular
• Luciferases
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, physiology)
• Mice
• Mice, Inbred C57BL
• Myoblasts (cytology, physiology, transplantation)
• Myocardial Infarction (mortality, pathology, physiopathology, therapy)
• Myocardium (pathology)
• Myocytes, Cardiac (cytology, physiology, transplantation)
• Recovery of Function
• Stroke Volume (physiology)
• Survival Analysis
• Transplantation, Autologous
• Ventricular Function, Left