title: Dynamic induction of pro-angiogenic milieu after transplantation of marrow-derived mesenchymal stem cells in experimental myocardial infarction.
abstract: BACKGROUND
  Cell-based pro-angiogenic therapy by bone marrow mesenchymal stem cells (MSCs) has been touted as a means to reducing the adverse effects of cardiac remodeling after myocardial infarction (MI). Milieu-dependent regulation of pro-angiogenic potential of MSCs after infarction remains to be elucidated. In this study, the effects of marrow-derived MSCs on the kinetics of angiogenesis signaling factors were investigated in a rabbit model of MI.
  
  
  METHODS
  MI was induced in rabbits, and the animals were randomized into two groups (cell transplantation and control, each group with 21 animals). 1 × 10(6) autologous marrow-derived MSCs were injected into the myocardium of the border zone after transfection with a green fluorescent protein (GFP) lentiviral reporter vector. Control animals received PBS vehicle only. Effect of the transplanted cells on the hearts was evaluated over time by pathological, immunofluorescence, western blotting, immuno-electron microscopy, and echocardiographic analyses.
  
  
  RESULTS
  Transplanted GFP-positive MSCs were enriched with time in the peri-infarct border zone with differentiation potential into three major cell types of the heart, including cardiomyocytes, endothelial cells, and smooth muscle cells, and there was significant augmentation of microvascular density. The transplanted cells could change the milieu of the injured myocardium to increase the expression levels of VEGF as well as the ratio of Ang-2 to Ang-1, and to reduce the ratio of phosphorylated Tie2 to Tie2.
  
  
  CONCLUSIONS
  An angiogenesis-promoting milieu was induced after the transplantation of marrow MSCs in the injured myocardium. Compared with the resident cells, the transplanted cells had a greater rate of cellular kinetics in the infarcted myocardium.
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran; Umbilical Cord Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz Branch Azad University, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Electronic address: nasirim@ut.ac.ir.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Nassiri
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Hossein
authors.initials: SH
authors.lastname: Ahmadi
authors.affiliation: Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Mohammadi
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Rabbani
authors.affiliation: Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Araghi
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (TAIWAN TECH), Taipei, 10607, Taiwan.
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinkhani
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011817:Rabbits
keywords: Acute myocardial infarction; Angiogenesis; Mesenchymal stem cells; Myocardial regeneration