title: Comparison of Efficacy of Endogenous and Exogenous IGF-I in Stimulating Matrix Production in Neonatal and Mature Chondrocytes.
abstract: OBJECTIVE
  The goal of this study was to compare the efficacy of endogenous upregulation of IGF-I by gene therapy and exogenous addition of insulin-like growth factor I (IGF-I) in enhancing proteoglycan synthesis by skeletally mature and neonatal chondrocytes. Chondrocyte transplantation therapy is a common treatment for focal cartilage lesions, with both mature and neonatal chondrocytes used as a cell source. Additionally, gene therapy strategies to upregulate growth factors such as IGF-I have been proposed to augment chondrocyte transplantation therapies.
  
  
  METHODS
  Both skeletally mature and neonatal chondrocytes were exposed to either an adeno-associated virus-based plasmid containing the IGF-I gene or exogenous IGF-I.
  
  
  RESULTS
  Analysis of IGF-I and glycosaminoglycan production using a 4-parameter dose-response model established a clear connection between the amount of IGF-I produced by cells and their biosynthetic response. Both neonatal and mature chondrocytes showed this relationship, but the sensitivities were quite different, with EC50 of 0.57 ng/mL for neonatal chondrocytes and EC50 of 8.70 ng/mL IGF-I for skeletally mature chondrocytes.
  
  
  CONCLUSIONS
  These data suggest that IGF-I gene therapy may be more effective with younger cell sources. Both cell types were less sensitive to exogenous IGF-I than endogenous IGF-I.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Izath N
authors.initials: IN
authors.lastname: Aguilar
authors.affiliation: Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA ; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Trippel
authors.affiliation: Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shuiliang
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA ; Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Bonassar
keywords: Cartilage Development; Gene Therapy; Growth Factor; Osteoarthritis