title: Bone marrow-derived cells contribute to infarct remodelling.
abstract: OBJECTIVE
  The paradigm that cardiac myocytes are non-proliferating and terminally differentiated cells has recently been challenged by several studies reporting the ability of bone marrow-derived cells (BMC) to transdifferentiate into cardiomyocytes. However, these results are controversial and could not be reproduced by others. Therefore, we studied the contribution and potential transdifferentiation of BMC into different cell types during the remodelling process in mouse hearts with experimental myocardial infarction.
  
  
  METHODS
  Mice (C57BL/6J) were sublethally irradiated, and BM from enhanced green fluorescent protein (eGFP)-transgenic mice was transplanted. Coronary artery ligation was performed 3 months later. The hearts were studied 7 days (n=13) and 21 days (n=12) after infarction. Immunohistochemical staining was performed using antibodies against titin, connexin 43, vimentin, SMemb alpha-smooth muscle actin, CD45, CD34, F4/80, BS-1, CD31, and eGFP. Sections were analyzed using fluorescence and confocal laser microscopy.
  
  
  RESULTS
  Success of BM transplantation was confirmed by FACS analysis. Occlusion of the coronary artery resulted in infarct sizes of 41+/-6% of the left ventricle. CD45+/eGFP+ inflammatory cells were found frequently after 7 days and to a lesser degree after 21 days. In 25 examined hearts, only 3 eGFP-positive cardiomyocytes were found. However, numerous BMC-derived fibroblasts and myofibroblasts were found in the infarct area. BMC contributed to scar tissue neoangiogenesis but not to angiogenesis in the periinfarct and remote zones.
  
  
  CONCLUSIONS
  Transdifferentiation of BMC into viable cardiomyocytes is a negligible event in normal repair processes after myocardial damage. BMC-derived fibroblasts and myofibroblasts as well as neoangiogenesis significantly contribute to post-infarction scar formation and might be important in scar tissue remodelling.
authors.affiliation: Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany. h.moellmann@kerckhoff.mpg.de
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
authors.forename: Holger M
authors.initials: HM
authors.lastname: Nef
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Ingo
authors.initials: I
authors.lastname: Pilz
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: Jutta
authors.initials: J
authors.lastname: Schaper
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.forename: Albrecht
authors.initials: A
authors.lastname: Elsässer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D018919:Neovascularization, Physiologic; D014184:Transplantation, Homologous; D014945:Wound Healing
chemical_list: D049452:Green Fluorescent Proteins