title: Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo.
abstract: OBJECTIVE
  We previously reported that human synovium contains cells that, after culture expansion, display properties of mesenchymal stem cells (MSCs). The objective of this study was to identify MSCs in native synovium in vivo.
  
  
  METHODS
  To identify stem cells in the synovium in vivo, a double nucleoside analog cell-labeling scheme was used in a mouse model of joint-surface injury. For labeling of slow-cycling cells, mice received iododeoxyuridine (IdU) for 30 days, followed by a 40-day washout period. For labeling of cells that proliferate after injury, mice underwent knee surgery to produce an articular cartilage defect and received chlorodeoxyuridine (CIdU) for 4 days, starting at multiple time points after surgery. Unoperated and sham-operated joints served as controls. Knee joint paraffin sections were analyzed by double and triple immunostaining to detect nucleoside analogs, conventional MSC markers, and chondrocyte-lineage markers.
  
  
  RESULTS
  Long-term-retaining, slow-cycling IdU-positive cells were detected in the synovium. At 4 days and 8 days after injury, there was marked proliferation of IdU-positive cells, which costained for CIdU. IdU-positive cells were nonhematopoietic, nonendothelial stromal cells, were distinct from pericytes, and stained positive for MSC markers. MSCs were phenotypically heterogeneous and located in topographically distinct niches in the lining layer and the subsynovial tissue. Twelve days after injury, double nucleoside-labeled cells within synovium were embedded in cartilage-specific metachromatic extracellular matrix and costained positive for the chondrocyte-lineage markers Sox9 and type II collagen.
  
  
  CONCLUSIONS
  Our findings provide the first evidence of the existence of resident MSCs in the knee joint synovium that undergo proliferation and chondrogenic differentiation following injury in vivo.
authors.affiliation: University of Aberdeen, Aberdeen, UK.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Kurth
authors.forename: Francesco
authors.initials: F
authors.lastname: Dell'accio
authors.forename: Vicki
authors.initials: V
authors.lastname: Crouch
authors.forename: Andrea
authors.initials: A
authors.lastname: Augello
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.forename: Cosimo
authors.initials: C
authors.lastname: De Bari
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D020219:Chondrogenesis / Q000502:physiology*; D007150:Immunohistochemistry; D007719:Knee Joint / Q000166:cytology* / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D055153:Stem Cell Niche / Q000166:cytology* / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology* / Q000502:physiology