title: Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo.
abstract: BACKGROUND
  Defects of articular cartilage are an unsolved problem in orthopaedics. In the present study, we tested the hypothesis that gene transfer of human fibroblast growth factor 2 (FGF-2) via transplantation of encapsulated genetically modified articular chondrocytes stimulates chondrogenesis in cartilage defects in vivo.
  
  
  METHODS
  Lapine articular chondrocytes overexpressing a lacZ or a human FGF-2 gene sequence were encapsulated in alginate and further characterized. The resulting lacZ or FGF-2 spheres were applied to cartilage defects in the knee joints of rabbits. In vivo, cartilage repair was assessed qualitatively and quantitatively at 3 and 14 weeks after implantation.
  
  
  RESULTS
  In vitro, bioactive FGF-2 was secreted, leading to a significant increase in the cell numbers in FGF-2 spheres. In vivo, FGF-2 continued to be expressed for at least 3 weeks without leading to differences in FGF-2 concentrations in the synovial fluid between treatment groups. Histological analysis revealed no adverse pathologic effects on the synovial membrane at any time point. FGF-2 gene transfer enhanced type II collagen expression and individual parameters of chondrogenesis, such as the cell morphology and architecture of the new tissue. Overall articular cartilage repair was significantly improved at both time points in vivo.
  
  
  CONCLUSIONS
  The data suggest that localized overexpression of FGF-2 enhances the repair of cartilage defects via stimulation of chondrogenesis, without adverse effects on the synovial membrane. These results may lead to the development of safe gene-based therapies for human articular cartilage defects.
authors.affiliation: Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kaul
authors.forename: Magali
authors.initials: M
authors.lastname: Cucchiarini
authors.forename: David
authors.initials: D
authors.lastname: Arntzen
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Dieter
authors.initials: D
authors.lastname: Kohn
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Trippel
authors.forename: Henning
authors.initials: H
authors.lastname: Madry
mesh_terms: D000464:Alginates / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000378:metabolism / Q000637:transplantation*; D024042:Collagen Type I / Q000096:biosynthesis; D024043:Collagen Type II / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007719:Knee Joint / Q000166:cytology / Q000276:immunology; D008297:Male; D011817:Rabbits; D013585:Synovitis / Q000276:immunology; D014162:Transfection; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: D000464:Alginates; D024042:Collagen Type I; D024043:Collagen Type II; D006025:Glycosaminoglycans; D016222:Fibroblast Growth Factor 2