title: Colony-stimulating factor-1 transfection of myoblasts improves the repair of failing myocardium following autologous myoblast transplantation.
abstract: OBJECTIVE
  Skeletal myoblasts are used in repair of ischaemic myocardium. However, a large fraction of grafted myoblasts degenerate upon engraftment. Colony-stimulating factor-1 (CSF-1) accelerates myoblast proliferation and angiogenesis. We hypothesized that CSF-1 overexpression improves myoblast survival and cardiac function in ischaemia-induced heart failure.
  
  
  RESULTS
  Three weeks following myocardial infarction, rats developed heart failure and received intramyocardial injections of mouse CSF-1-transfected or untransfected primary autologous rat myoblasts, recombinant human CSF-1, mouse CSF-1 expressing plasmids, or culture medium. Tissue gene and protein expression was measured by quantitative RT-PCR (reverse transcription-polymerase chain reaction) and western blotting. Fluorescence imaging and immunocytochemistry were used to analyse myoblasts, endothelial cells, macrophages, and infarct wall thickening. Electrocardiograms were recorded online using a telemetry system. Left ventricular function was assessed by echocardiography over time, and improved significantly only in the CSF-1-overexpressing myoblast group. CSF-1-overexpression enhanced myoblast numbers and was associated with an increased infarct wall thickness, enhanced angiogenesis, increased macrophage recruitment and upregulated matrix metalloproteases (MMP)-2 and -12 in the zone bordering the infarction. Transplantation of CSF-1-overexpressing myoblasts did not result in major arrhythmias.
  
  
  CONCLUSIONS
  Autologous intramyocardial transplantation of CSF-1 overexpressing myoblasts might be a novel strategy in the treatment of ischaemia-induced heart failure.
authors.affiliation: Department of Cardio-Thoracic Surgery, Medical University of Vienna, Waehringerguertel 18-20, A-1090 Vienna, Austria. seyedhossein.aharinejad@meduniwien.ac.at
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
authors.forename: Dietmar
authors.initials: D
authors.lastname: Abraham
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
authors.forename: Karin
authors.initials: K
authors.lastname: Zins
authors.forename: Michael
authors.initials: M
authors.lastname: Hofmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Michlits
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Karin
authors.initials: K
authors.lastname: Macfelda
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Karola
authors.initials: K
authors.lastname: Trescher
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D051379:Mice; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D053505:Matrix Metalloproteinases, Secreted