title: Bone marrow cell-induced protection of the human myocardium: characterization and mechanism of action.
abstract: OBJECTIVE
  The mechanism of the putative beneficial effect of myocardial transplantation of bone marrow cells remains unclear. We studied the protective properties of bone marrow cells on the human myocardium and investigated the underlying mechanism.
  
  
  METHODS
  Bone marrow cells and the right atrial appendage were obtained from patients undergoing elective cardiac surgery. Myocardial slices were subjected to 90 minutes of simulated ischemia/120 minutes of reoxygenation at 37 degrees C following various protocols. Tissue injury was assessed by creatine kinase released into the media during the reoxygenation period, and myocardial necrosis and apoptosis were determined by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (percent of aerobic control).
  
  
  RESULTS
  Autologous unfractionated bone marrow cells significantly reduced myocardial injury. Maximal protection was obtained with 5 x 10(6) autologous cells (approximately 1.5 x 10(5) cells/mg wet myocardium) that caused a reduction in creatine kinase release and cell death by necrosis and apoptosis of 70% to 80%. Allogenic bone marrow cells were as protective as the autologous cells and their effect was unaffected by prior frozen storage or culturing. Similar myocardial protection was also attained when bone marrow cells were present only before or during ischemia, or during reoxygenation, a benefit that was comparable with that of ischemic preconditioning. Conditioned media by the bone marrow cells was sufficient to induce protection, which was abolished by the selective insulin-like growth factor-1 receptor blocker PQ401.
  
  
  CONCLUSIONS
  Bone marrow cells possess potent myocardial protective properties that are triggered by a secreted factor or factors and mediated by insulin-like growth factor-1 receptor. These results have important clinical implications for the therapeutic use of bone marrow cells in ischemic heart disease and for the design of future clinical studies.
authors.affiliation: Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
authors.forename: Vien Khach
authors.initials: VK
authors.lastname: Lai
authors.forename: José
authors.initials: J
authors.lastname: Linares-Palomino
authors.forename: Bernardo
authors.initials: B
authors.lastname: Nadal-Ginard
authors.forename: Manuel
authors.initials: M
authors.lastname: Galiñanes
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology*; D016923:Cell Death; D003402:Creatine Kinase / Q000032:analysis; D006321:Heart / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000502:physiology; D017202:Myocardial Ischemia / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis
chemical_list: D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003402:Creatine Kinase