title: Embryonic cardiomyocyte, but not autologous stem cell transplantation, restricts infarct expansion, enhances ventricular function, and improves long-term survival.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Leonie E
authors.initials: LE
authors.lastname: Paulis
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Klein
authors.forename: Alexander
authors.initials: A
authors.lastname: Ghanem
authors.forename: Tessa
authors.initials: T
authors.lastname: Geelen
authors.forename: Bram F
authors.initials: BF
authors.lastname: Coolen
authors.forename: Martin
authors.initials: M
authors.lastname: Breitbach
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D018421:Cardiomyoplasty / Q000379:methods*; D004622:Embryo, Mammalian; D017930:Genes, Reporter; D007273:Injections, Intramuscular; D008156:Luciferases; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D032446:Myoblasts / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D020127:Recovery of Function; D013318:Stroke Volume / Q000502:physiology; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left
chemical_list: D008156:Luciferases