title: Protective effects of human amniotic fluid stem cells in a model of aorta allograft vasculopathy in rats.
abstract: BACKGROUND
  Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune inflammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid-derived stem cells (hAFSCs), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, display immunomodulatory properties. hAFSCs express mesenchymal and embryonic markers, show high proliferation rates; however, they do not induce tumor formation, and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation.
  
  
  METHODS
  Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into three groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n = 8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n = 8); and ALLO + hAFSC, ALLO rats treated with hAFSC (10(6) cells; n = 8). Histological analysis and immunohistochemistry were performed 30 days posttransplantation.
  
  
  RESULTS
  The ALLO group developed a robust aortic neointimal formation (208.7 ± 25.4 μm) accompanied by a significant high number of ED1+ (4845 ± 841 cells/mm2) and CD43+ cells (4064 ± 563 cells/mm2), and enhanced expression of α-smooth muscle actin in the neointima (25 ± 6%). Treatment with hAFSC diminished neointimal thickness (180.7 ± 23.7 μm) and induced a significant decrease of ED1+ (1100 ± 276 cells/mm2), CD43+ cells (1080 ± 309 cells/μm2), and α-smooth muscle actin expression 8 ± 3% in the neointima.
  
  
  CONCLUSIONS
  These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.
authors.affiliation: Laboratory of Cellular, Genetic, and Molecular Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Santana
authors.forename: H
authors.initials: H
authors.lastname: Dellê
authors.forename: R C
authors.initials: RC
authors.lastname: Cavaglieri
authors.forename: M A B
authors.initials: MA
authors.lastname: Lopes
authors.forename: R P V
authors.initials: RP
authors.lastname: Francisco
authors.forename: M
authors.initials: M
authors.lastname: Zugaib
authors.forename: S P
authors.initials: SP
authors.lastname: Bydlowski
authors.forename: I L
authors.initials: IL
authors.lastname: Noronha
mesh_terms: D000199:Actins / Q000378:metabolism; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D001018:Aortic Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D053686:Fetal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D058426:Neointima; D016377:Organ Transplantation / Q000009:adverse effects*; D039904:Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors
chemical_list: D000199:Actins; D015415:Biomarkers; C498862:Acta2 protein, rat