title: Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo.
abstract: OBJECTIVE
  The combination of chondrogenic factors might be necessary to adequately stimulate articular cartilage repair. In previous studies, enhanced repair was observed following transplantation of chondrocytes overexpressing human insulin-like growth factor I (IGF-I) or fibroblast growth factor 2 (FGF-2). Here, the hypothesis that co-overexpression of IGF-I and FGF-2 by transplanted articular chondrocytes enhances the early repair of cartilage defects in vivo and protects the neighbouring cartilage from degeneration was tested.
  
  
  METHODS
  Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or co-transfected with the IGF-I and FGF-2 gene, encapsulated in alginate and transplanted into osteochondral defects in the knee joints of rabbits in vivo.
  
  
  RESULTS
  After 3 weeks, co-overexpression of IGF-I/FGF-2 improved the macroscopic aspect of defects without affecting the synovial membrane. Immunoreactivity to type-I collagen, an indicator of fibrocartilage, was significantly lower in defects receiving IGF-I/FGF-2 implants. Importantly, combined IGF-I/FGF-2 overexpression significantly improved the histological repair score. Most remarkably, such enhanced cartilage repair was correlated with a 2.1-fold higher proteoglycan content of the repair tissue. Finally, there were less degenerative changes in the cartilage adjacent to the defects treated with IGF-I/FGF-2 implants.
  
  
  CONCLUSIONS
  The data demonstrate that combined gene delivery of therapeutic growth factors to cartilage defects may have value to promote cartilage repair. The results also suggest a protective effect of IGF-I/FGF-2 co-overexpression on the neighbouring articular cartilage. These findings support the concept of implementing gene transfer strategies for articular cartilage repair in a clinical setting.
authors.affiliation: Experimental Orthopaedics and Osteoarthritis Research, Saarland University, Kirrbergerstrasse, Building 37, 66421, Homburg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Orth
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: Zurakowski
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Dieter
authors.initials: D
authors.lastname: Kohn
authors.forename: Henning
authors.initials: H
authors.lastname: Madry
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002682:Chinchilla; D019902:Chondrocytes / Q000378:metabolism* / Q000637:transplantation*; D020219:Chondrogenesis / Q000502:physiology*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D050724:Fractures, Cartilage / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D014945:Wound Healing / Q000502:physiology
chemical_list: D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I