Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts

Hum Gene Ther. 2001 Sep 20;12(14):1805-13. doi: 10.1089/104303401750476294.

Abstract

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Arthritis / metabolism
  • Blotting, Northern
  • Cartilage / chemistry*
  • Cartilage / metabolism
  • Cell Differentiation
  • Cell Division
  • Chondrocytes / metabolism
  • DNA, Complementary / metabolism
  • Fibroblasts / metabolism*
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Hyalin / metabolism*
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Mice
  • Protein Binding
  • RNA, Messenger / metabolism
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta1
  • Transgenes

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1