title: Flanking recipient vasculature, not circulating progenitor cells, contributes to endothelium and smooth muscle in murine allograft vasculopathy.
abstract: OBJECTIVE
  The prevailing view assumes that circulating endothelial and smooth muscle progenitor cells participate in allograft vasculopathy (AV), although the seminal studies in the field were not designed to distinguish between circulating and migrating cells of recipient origin. We developed a double-transplantation technique to overcome this problem and reinvestigated the origin of endothelial cells (ECs) and smooth muscle cells (SMCs) in murine AV.
  
  
  RESULTS
  Carotid artery segments from BALB/c mice were allografted to apolipoprotein E(-/-) B6 mice with or without a "flanking" isograft interpositioned between the allograft and the recipient artery. Either recipient mice or interpositioned isografts expressed enhanced green fluorescent protein, and consequently, cells migrating into the allograft from the flanking vasculature could easily be tracked and distinguished from recruited circulating cells. Without immunosuppression, allograft donor cells vanished as expected, and AV developed by replacement and accumulation of ECs and SMCs of recipient origin. The double transplantation models revealed that all ECs and SMCs in AV had migrated into the allograft from the flanking vasculature without any contribution from putative progenitor cells in the blood.
  
  
  CONCLUSIONS
  Migrating cells from the flanking vasculature, not circulating progenitor cells, are the source of recipient-derived ECs and SMCs in murine AV.
authors.affiliation: Atherosclerosis Research Unit, Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark. mette.hagensen@ki.au.dk
authors.forename: Mette K
authors.initials: MK
authors.lastname: Hagensen
authors.forename: Jeong
authors.initials: J
authors.lastname: Shim
authors.forename: Erling
authors.initials: E
authors.lastname: Falk
authors.forename: Jacob F
authors.initials: JF
authors.lastname: Bentzon
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D002465:Cell Movement; D058948:Cell Tracking; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D058017:Vascular Grafting
chemical_list: D001057:Apolipoproteins E; D007166:Immunosuppressive Agents; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins