Continuous Transforming Growth Factor beta1 Secretion by Cell-Mediated Gene Therapy Maintains Chondrocyte Redifferentiation

Tissue Eng. Jan-Feb 2005;11(1-2):310-8. doi: 10.1089/ten.2005.11.310.

Abstract

One of the most important factors in the production of cartilage is transforming growth factor beta1 (TGF-beta1). To obtain sustained release of TGF-beta1, a cell-mediated gene therapy technique was introduced. We infected chondrocytes with a retroviral vector carrying the TGF-beta1 gene. The single clone derivative showed sustained TGF-beta1 secretion. It also showed constitutive type II collagen expression. Whereas the TGF-beta1 protein itself is unable to induce formation of cartilage in vivo, human chondrocytes engineered to express a retroviral vector encoding TGF-beta1 showed cartilage formation in vivo when cells were injected into nude mice intradermally. These data suggest that cell-mediated gene therapy using TGF-beta1 as a transgene would be a promising treatment for osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cell Differentiation*
  • Cell Transplantation
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Chondrocytes / transplantation
  • Collagen Type II / drug effects
  • Collagen Type II / metabolism
  • Feasibility Studies
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Retroviridae / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Transgenes
  • Transplantation, Heterologous

Substances

  • Collagen Type II
  • TGFB1 protein, human
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1