title: Progenitor cell mobilizing treatments prevent experimental transplant arteriosclerosis.
abstract: OBJECTIVE
  Vascular rejection after organ transplantation is characterized by an arterial occlusive lesion, resulting from intimal proliferation occurring in response to arterial wall immune aggression. Our hypothesis is that an early endothelial repair may prevent vascular graft rejection. The aim of the current study was to compare different pharmacologic progenitor cell mobilizing treatments for their protective effects against vascular rejection.
  
  
  RESULTS
  Aortic transplants were made from balb/c donor to C57Bl/6 recipient mice. Three different mobilizing pharmacologic agents were used: low molecular weight fucoidan (LMWF), simvastatin, and AMD3100. The circulating levels of progenitor cells were found to be increased by all three treatments, as determined by flow cytometry. For each treatment, the design was: treated allografts, nontreated allografts, treated isografts, and nontreated isografts. After 21 d, morphometric and immunohistochemical analyses were performed. We found that the three treatments significantly reduced intimal proliferation, compared with nontreated allografts. This was associated with intimal re-endothelialization of the grafts. Further, in chimeric mice that had previously received GFP-transgenic bone marrow transplantation, GFP-positive cells were found in the vascular allograft intima, indicating that re-endothelialization was, at least partly, due to the recruitment of bone marrow-derived, presumably endothelial progenitor circulating cells.
  
  
  CONCLUSIONS
  In this aortic allograft model, three different mobilizing treatments were found to partially prevent vascular transplant rejection. Bone marrow-derived progenitor cells mobilized by the three treatments may play a direct role in the endothelial repair process and in the suppression of intimal proliferation.
authors.affiliation: Inserm U644, Institute for Biomedical Research, Rouen University, Rouen, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Roux
authors.forename: Ebba
authors.initials: E
authors.lastname: Brakenhielm
authors.forename: Caroline
authors.initials: C
authors.lastname: Freguin-Bouillant
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Henry
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Didier
authors.initials: D
authors.lastname: Plissonnier
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D001011:Aorta / Q000637:transplantation*; D001161:Arteriosclerosis / Q000517:prevention & control*; D001596:Benzylamines; D000080027:Cyclams; D004730:Endothelium, Vascular / Q000187:drug effects; D006084:Graft Rejection / Q000517:prevention & control*; D049452:Green Fluorescent Proteins / Q000235:genetics; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008970:Molecular Weight; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000924:Anticholesteremic Agents; D000925:Anticoagulants; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011134:Polysaccharides; D049452:Green Fluorescent Proteins; C007789:fucoidan; D019821:Simvastatin; C088327:plerixafor