title: Functional regeneration of ischemic myocardium by transplanted cells overexpressing stromal cell-derived factor-1 (SDF-1): intramyocardial injection versus scaffold-based application.
abstract: OBJECTIVE
  Stromal cell-derived factor-1 (SDF-1) is a potent chemotaxin. Increased SDF-1 levels can be found in ischemic myocardium and might protect against ischemia-reperfusion injury. We hypothesized that transplantation of stem cells overexpressing SDF-1 might improve cardiac function after myocardial infarction (MI). We compared intramyocardial injection with a scaffold-based application of SDF-1-transfected cells.
  
  
  METHODS
  Skeletal myoblasts (SkMs) were isolated and expanded from newborn Lewis rats. Cells were transfected with pcDNA3-huSDF-1 and seeded on polyurethane (PU) scaffolds or diluted in medium for cell injection. Two weeks after myocardial infarction, seeded scaffolds were implanted epicardially into rats (group: PU-SDF-1-SkM) or the injection solution was applied intramyocardially (Inj-SDF-1-SkM). Additional groups were treated with non-transfected myoblasts either by injection (Inj-SkM) or by scaffold-based application (PU-SkM) or received a sham operation (Sham). Before this intervention and 6 weeks later, hemodynamic parameters were measured. Infarction size and neovascularization were assessed by histology at study end.
  
  
  RESULTS
  In sham animals, we detected a clear decrease in systolic function from intervention to study end. In group Inj-SkM and PU-SkM, all hemodynamic parameters that were assessed remained unchanged during observation time. Systolic function as measured by dP/dt(max) and SB-Emax was significantly improved in groups Inj-SDF-1-SkM and PU-SDF-1-SkM at study end without a difference between the two SDF-1 groups. Diastolic function measured by post-interventional dP/dt(min) was also increased in group Inj-SDF-1-SkM but not in PU-SDF-1-SkM. Histological analysis revealed a reduced infarction size in all treatment groups at study end but enhanced neovascularization was not observable.
  
  
  CONCLUSIONS
  Transplantation of myoblasts overexpressing SDF-1 improves cardiac function after MI. The restoration of hemodynamic parameters is accompanied by a reduction in infarction size. This reverse remodeling capacity is independent of a scaffold-based application of the SDF-1-transfected cells.
authors.affiliation: Department of Cardiovascular Surgery, University Medical Center Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Blumenthal
authors.forename: Annika
authors.initials: A
authors.lastname: Poppe
authors.forename: Peter
authors.initials: P
authors.lastname: Golsong
authors.forename: Philipp
authors.initials: P
authors.lastname: Blanke
authors.forename: Bartosz
authors.initials: B
authors.lastname: Rylski
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.forename: Matthias
authors.initials: M
authors.lastname: Siepe
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D007267:Injections; D008297:Male; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology; D054457:Tissue Scaffolds; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
chemical_list: D054377:Chemokine CXCL12