title: Granulation tissue is altered after intramyocardial and intracoronary bone marrow-derived cell transfer for experimental acute myocardial infarction.
abstract: BACKGROUND
  Bone marrow-derived mononuclear cell (BMMC) treatment in acute myocardial infarction (AMI) has been shown to have a beneficial effect. Our objective was to study in detail the histopathological process after the cell therapy after intramyocardial (IM) or intracoronary (IC) administration of BMMCs following experimental AMI.
  
  
  METHODS
  Twenty-fours pigs were randomized to the IM group (n=8), the IC group (n=8), and the control group (n=8).After 90 min of transient occlusion of the circumflex coronary artery, BMMCs were injected either intramyocardially or by a transfemoral catheter into the circumflex coronary artery. Echocardiography was performed preoperatively, postoperatively, and after a 21-day recovery period. The heart biopsies were examined histopathologically. Volumetric ex vivo CT scan was performed to evaluate calcification of the infarcted myocardium.
  
  
  RESULTS
  The ejection fraction (EF) showed significant recovery in the IM group compared to the control group at Day 21 (P=.05). Despite beneficial histological changes in the infarction site in the IC group, compared to the control group, EF failed to recover. Reduction of collagen density that depicts scar formation was seen in both cell therapy groups compared to the control (P<.001). The number of mitotic cells was higher in the control group compared to the cell therapy groups (P<.001). The IC and IM groups differed significantly from each other in muscle-specific actin staining (P<.001) and smooth muscle actin staining (P<.004). The IM therapy group showed higher density for both stainings. Additionally, macrophage density was higher in the IC group compared to the IM and control groups (P<.002). Both cell therapy regimens substantially diminished tissue calcification; due to the large variation, the effect was not statistically significant.
  
  
  CONCLUSIONS
  BMMC therapy launches cellular changes that affect mostly the repair process in the granulation tissue. The cell transplantation method might have some effect on the magnitude of the effect.
authors.affiliation: Department of Surgery, Oulu University Hospital, University of Oulu and Clinical Research Center, 90221 Oulu, Finland. jussi.makela@oulu.fi
authors.forename: Jussi
authors.initials: J
authors.lastname: Makela
authors.forename: Fredrik
authors.initials: F
authors.lastname: Yannopoulos
authors.forename: Kari
authors.initials: K
authors.lastname: Ylitalo
authors.forename: Timo
authors.initials: T
authors.lastname: Makikallio
authors.forename: Siri
authors.initials: S
authors.lastname: Lehtonen
authors.forename: Elisa
authors.initials: E
authors.lastname: Lappi-Blanco
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dahlbacka
authors.forename: Eija
authors.initials: E
authors.lastname: Rimpilainen
authors.forename: Hanna
authors.initials: H
authors.lastname: Kaakinen
authors.forename: Tatu
authors.initials: T
authors.lastname: Juvonen
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
authors.forename: Vesa
authors.initials: V
authors.lastname: Anttila
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006097:Granulation Tissue / Q000378:metabolism / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D020127:Recovery of Function; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D015415:Biomarkers