title: Role for circulating osteogenic precursor cells in aortic valvular disease.
abstract: OBJECTIVE
  Approximately 13% of aortic valves removed from patients with end-stage aortic valve disease contain heterotopic ossification (HO). Recently, we identified a novel population of circulating osteogenic precursor (COP) cells that are derived from bone marrow and have the capability to form bone. These cells are identified by coexpression of the osteogenic marker type 1 collagen or osteoclacin and the hematopoietic marker CD45. We tested the hypothesis that these cells may contribute to heart valve stenosis.
  
  
  RESULTS
  Quantification of CD45(+) osteoclacin(+) COP cells by flow cytometry showed that they represent up to 1.1% of mononuclear cells. Clonally derived COP cells produce bone morphogenetic proteins 2 and 4 by immunohistochemical analysis. We reviewed 105 cases of end-stage aortic valvular disease and confirmed HO in 13 archived specimens. Using immunohistochemistry, we identified COP cells by coexpression of CD45 and type 1 collagen. There was a statistically significant association between the presence of COP cells and early HO lesions. COP cells were negligible in regions of unaffected valve leaflets (no HO) from the same individuals.
  
  
  CONCLUSIONS
  This study provides the first evidence that osteogenic cells in the blood home to sites of vascular injury and are associated with HO formation in heart valves.
authors: Department of Medicine, University of Pennsylvania School of Medicine, 36th St & Hamilton Walk, Philadelphia, PA 19104-6081, USA.
authors: Kevin P
authors: KP
authors: Egan
authors: Jung-Hoon
authors: JH
authors: Kim
authors: Emile R
authors: ER
authors: Mohler
authors: Robert J
authors: RJ
authors: Pignolo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D009999:Ossification, Heterotopic / Q000473:pathology / Q000503:physiopathology*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D012189:Retrospective Studies
chemical_list: D024042:Collagen Type I; D015675:Osteocalcin; D017493:Leukocyte Common Antigens