title: Non-bone marrow origin of neointimal smooth muscle cells in experimental in-stent restenosis in rats.
abstract: OBJECTIVE
  To determine the contribution of bone marrow (BM)-derived cells in in-stent restenosis (ISR) and transplant arteriosclerosis (TA).
  
  
  METHODS
  Non-transgenic rats WT F344(TG) (n = 3) received stent implantation 6 weeks after lethal total body irradiation and suppletion with bone marrow from a R26-hPAP transgenic rat. After 4 weeks the abdominal aortas were harvested, the stent was quickly removed, the abdominal aorta was snap-frozen in liquid nitrogen and 5 mum cryosections for stainings were cut. Additionally, DA aortic allografts were transplanted into WT F344(TG) (n = 3) and R26-hPAP(WT) (n = 3) BM-chimeric recipients. Immunohistochemistry (hPAP staining) and immunofluorescence (hPAP, alpha-SMA and OX1) was performed on all sections.
  
  
  RESULTS
  Few hPAP-positive cells were observed in the neointima. Double stainings of hPAP-positive areas showed no alpha-SMA colocalization; OX-1 did show colocalization.
  
  
  CONCLUSIONS
  Non-BM-derived cells are the predominant source of neointimal cells in ISR and TA. Vascular wall-derived progenitor cells may rather be the source of SMCs that contribute to ISR and TA, which may have implications for our quest for new therapeutic targets to treat these vasculopathies.
authors.affiliation: Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. r.groenewegen@med.umcg.nl
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Groenewegen
authors.forename: Geanina
authors.initials: G
authors.lastname: Onuta
authors.forename: Maaike
authors.initials: M
authors.lastname: Goris
authors.forename: André
authors.initials: A
authors.lastname: Zandvoort
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Jan
authors.initials: J
authors.lastname: Rozing
authors.forename: Bart J G L
authors.initials: BJ
authors.lastname: de Smet
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roks
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
mesh_terms: D000469:Alkaline Phosphatase; D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000473:pathology* / Q000601:surgery / Q000637:transplantation; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation; D001854:Bone Marrow Cells / Q000201:enzymology / Q000473:pathology*; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006083:Graft Occlusion, Vascular / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D015607:Stents; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000201:enzymology / Q000473:pathology*
chemical_list: D000469:Alkaline Phosphatase