title: Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction.
abstract: BACKGROUND
  Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.
  
  
  RESULTS
  In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.
  
  
  CONCLUSIONS
  Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.
authors.affiliation: Deutsches Herzzentrum der Technischen Universität München, Lazarettstr 36, 80636 München, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stein
authors.forename: Martina
authors.initials: M
authors.lastname: Knödler
authors.forename: Markus
authors.initials: M
authors.lastname: Makowski
authors.forename: Sandra
authors.initials: S
authors.lastname: Kühnel
authors.forename: Stefan
authors.initials: S
authors.lastname: Nekolla
authors.forename: Alexandra
authors.initials: A
authors.lastname: Keithahn
authors.forename: Eliane
authors.initials: E
authors.lastname: Weidl
authors.forename: Philip
authors.initials: P
authors.lastname: Groha
authors.forename: Maren
authors.initials: M
authors.lastname: Schürmann
authors.forename: Atti
authors.initials: A
authors.lastname: Saraste
authors.forename: Rene
authors.initials: R
authors.lastname: Botnar
authors.forename: Robert Aj
authors.initials: RA
authors.lastname: Oostendorp
authors.forename: Ilka
authors.initials: I
authors.lastname: Ott
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D004921:Erythropoietin / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D011923:Rats, Nude; D020127:Recovery of Function / Q000187:drug effects; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D004921:Erythropoietin