title: Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function.
abstract: BACKGROUND
  Mesenchymal precursor cells (MPCs) are a specific Stro-3+ subpopulation of mesenchymal stem cells isolated from bone marrow. MPCs exert extensive cardioprotective effects, and are considered to be immune privileged.
  
  
  OBJECTIVE
  This study assessed the safety, feasibility, and efficacy of intracoronary delivery of allogeneic MPCs directly after acute myocardial infarction in sheep.
  
  
  RESULTS
  Initially, intracoronary delivery conditions were optimized in 20 sheep. These conditions were applied in a randomized study of 68 sheep with an anterior acute myocardial infarction. Coronary flow was monitored during MPC infusion, and cardiac function was assessed using invasive hemodynamics and echocardiography at baseline and during 8 weeks follow-up. Coronary flow remained within thrombolysis in myocardial infarction III definitions in all sheep during MPC infusion. Global left ventricular ejection fraction as measured by pressure-volume loop analysis deteriorated in controls to 40.7±2.6% after 8 weeks. In contrast, MPC treatment improved cardiac function to 52.8±0.7%. Echocardiography revealed significant improvement of both global and regional cardiac functions. Infarct size decreased by 40% in treated sheep, whereas infarct and border zone thickness were enhanced. Left ventricular adverse remodeling was abrogated by MPC therapy, resulting in a marked reduction of left ventricular volumes. Blood vessel density increased by >50% in the infarct and border areas. Compensatory cardiomyocyte hypertrophy was reduced in border and remote segments, accompanied by reduced collagen deposition and apoptosis. No microinfarctions in remote myocardial segments or histological abnormalities in unrelated organs were found.
  
  
  CONCLUSIONS
  Intracoronary infusion of allogeneic MPCs is safe, feasible, and markedly effective in a large animal model of acute myocardial infarction.
authors: Molecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, The Netherlands.
authors: Jaco H
authors: JH
authors: Houtgraaf
authors: Renate
authors: R
authors: de Jong
authors: Kushan
authors: K
authors: Kazemi
authors: Daphne
authors: D
authors: de Groot
authors: Tycho I G
authors: TI
authors: van der Spoel
authors: Fatih
authors: F
authors: Arslan
authors: Imo
authors: I
authors: Hoefer
authors: Gerard
authors: G
authors: Pasterkamp
authors: Silviu
authors: S
authors: Itescu
authors: Felix
authors: F
authors: Zijlstra
authors: Marcel L
authors: ML
authors: Geleijnse
authors: Patrick W
authors: PW
authors: Serruys
authors: Henricus J
authors: HJ
authors: Duckers
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D005500:Follow-Up Studies; D007261:Infusions, Intra-Arterial; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D011897:Random Allocation; D012756:Sheep; D014184:Transplantation, Homologous; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: cell transplantation; mesenchymal progenitor cell; mesenchymal stem cell; percutaneous coronary intervention tissue therapy