title: Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.
abstract: BACKGROUND
  Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation.
  
  
  OBJECTIVE
  The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation.
  
  
  METHODS
  Subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day before surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At the time of transplantation, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject.
  
  
  RESULTS
  Six subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histological analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34- injected areas.
  
  
  CONCLUSIONS
  Tissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection.
authors: Department of Medicine, University of Washington School of Medicine, Seattle, Washington. Electronic address: april@uw.edu.
authors: April
authors: A
authors: Stempien-Otero
authors: Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Deri
authors: D
authors: Helterline
authors: Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Tabitha
authors: T
authors: Plummer
authors: Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Stephen
authors: S
authors: Farris
authors: Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Andrew
authors: A
authors: Prouse
authors: The Mountain-Whisper-Light Statistics, Seattle, Washington.
authors: Nayak
authors: N
authors: Polissar
authors: The Mountain-Whisper-Light Statistics, Seattle, Washington.
authors: Derek
authors: D
authors: Stanford
authors: Department of Surgery, University of Washington School of Medicine, Seattle, Washington.
authors: Nahush A
authors: NA
authors: Mokadam
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D009202:Cardiomyopathies / Q000175:diagnosis / Q000628:therapy*; D005260:Female; D016027:Heart Transplantation / Q000379:methods; D006352:Heart Ventricles; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000628:therapy*
keywords: angiogenesis; cell therapy; heart failure; ischemia