title: Matrix-associated implantation of predifferentiated mesenchymal stem cells versus articular chondrocytes: in vivo results of cartilage repair after 1 year.
abstract: BACKGROUND
  The use of predifferentiated mesenchymal stem cells (MSC) leads to better histological results compared with undifferentiated MSC in sheep. This raises the need for a longer term follow-up study and comparison with a clinically established method.
  
  
  OBJECTIVE
  We hypothesized that chondrogenic in vitro predifferentiation of autologous MSC embedded in a collagen I hydrogel leads to better structural repair of a chronic osteochondral defect in an ovine stifle joint after 1 year. We further hypothesized that resulting histological results would be comparable with those of chondrocyte-seeded matrix-associated autologous chondrocyte transplantation (MACT).
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Predifferentiation period of ovine MSC within collagen gel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, 2 osteochondral lesions (7-mm diameter) were created at the medial femoral condyles of the hind legs in 9 sheep. Implantation of MSC gels was performed 6 weeks after defect creation. Thirty-six defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated MSC gels (pre-MSC gels), (2) undifferentiated MSC gels (un-MSC gels), (3) MACT gels, and (4) untreated controls (UC). Histological, immunohistochemical, and radiological evaluations followed after 12 months.
  
  
  RESULTS
  After 12 months in vivo, pre-MSC gels showed significantly better histological outcome compared with un-MSC gels and UC. Compared with MACT gels, the overall scores were higher for O'Driscoll and International Cartilage Repair Society (ICRS). The repair tissue of the pre-MSC group showed immunohistochemical detection of interzonal collagen type II staining. Radiological evaluation supported superior bonding of pre-MSC gels to perilesional native cartilage. Compared with previous work by our group, no degradation of the repair tissue between 6 and 12 months in vivo, particularly in pre-MSC gels, was observed.
  
  
  CONCLUSIONS
  Repair of chronic osteochondral defects with collagen hydrogels composed of chondrogenically predifferentiated MSC shows no signs of degradation after 1 year in vivo. In addition, pre-MSC gels lead to partially superior histological results compared with articular chondrocytes.
  
  
  CONCLUSIONS
  The results suggest an encouraging method for future treatment of focal osteochondral defects without donor site morbidity by harvesting articular chondrocytes.
authors.affiliation: Department of Trauma and Reconstructive Surgery, University of Leipzig, Leipzig, Germany. Bastian.Marquass@medizin.uni-leipzig.de
authors.forename: Bastian
authors.initials: B
authors.lastname: Marquass
authors.forename: Ronny
authors.initials: R
authors.lastname: Schulz
authors.forename: Pierre
authors.initials: P
authors.lastname: Hepp
authors.forename: Matthias
authors.initials: M
authors.lastname: Zscharnack
authors.forename: Thomas
authors.initials: T
authors.lastname: Aigner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schmidt
authors.forename: Frank
authors.initials: F
authors.lastname: Stein
authors.forename: Robert
authors.initials: R
authors.lastname: Richter
authors.forename: Georg
authors.initials: G
authors.lastname: Osterhoff
authors.forename: Gabriele
authors.initials: G
authors.lastname: Aust
authors.forename: Christoph
authors.initials: C
authors.lastname: Josten
authors.forename: Augustinus
authors.initials: A
authors.lastname: Bader
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000637:transplantation*; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D012756:Sheep; D013264:Stifle
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II