title: Mitral valve endothelial cells with osteogenic differentiation potential.
abstract: OBJECTIVE
  Cardiac valvular endothelium is unique in its ability to undergo endothelial-to-mesenchymal transformation, a differentiation process that is essential for valve development and has been proposed as mechanism for replenishing the interstitial cells of mature valves. We hypothesized that the valvular endothelium contains endothelial cells that are direct precursors to osteoblastic valvular interstitial cells (VICs).
  
  
  RESULTS
  Clonal cell populations from ovine mitral valve leaflets were isolated by single cell plating. Mitral valvular endothelial and mesenchymal clones were tested for osteogenic, adipogenic, and chondrogenic differentiation, determined by the expression of lineage-specific markers. Mitral valvular endothelial clones showed a propensity for osteogenic, as well as chondrogenic differentiation that was comparable to a mitral valvular VIC clone and to bone marrow-derived mesenchymal stem cells. Osteogenic differentiation was not detected in nonvalvular endothelial cells. Regions of osteocalcin expression, a marker of osteoblastic differentiation, were detected along the endothelium of mitral valves that had been subjected in vivo to mechanical stretch.
  
  
  CONCLUSIONS
  Mitral valve leaflets contain endothelial cells with multilineage mesenchymal differentiation potential, including osteogenic differentiation. This unique feature suggests that postnatal mitral valvular endothelium harbors a reserve of progenitor cells that can contribute to osteogenic and chondrogenic VICs.
authors.affiliation: Vascular Biology Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Wylie-Sears
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Yang
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
mesh_terms: D050156:Adipogenesis; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D020219:Chondrogenesis; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D006351:Heart Valves / Q000166:cytology*; D010006:Osteoblasts / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D010641:Phenotype; D012756:Sheep; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015675:Osteocalcin