title: Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.
abstract: BACKGROUND
  We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one.
  
  
  METHODS
  We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed.
  
  
  RESULTS
  The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used.
  
  
  CONCLUSIONS
  The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Guillén-García
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Rodríguez-Iñigo
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Guillén-Vicente
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Caballero-Santos
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Guillén-Vicente
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Stephen
authors.initials: S
authors.lastname: Abelow
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Giménez-Gallego
authors.affiliation: Unidad de Investigación, Clínica CEMTRO, Madrid, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: López-Alcorocho
keywords: animal models; articular cartilage; chondrocytes; knee