Scientific article

Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament

Published inTissue engineering, vol. 5, no. 5, p. 435-442
Publication date1999

The anterior cruciate ligament (ACL) has poor capabilities of healing. Maturation or "ligamentization" of the ACL following autograft or allograft reconstruction has been found slow and remains under investigation. In vitro and in vivo studies have shown that platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), and epidermal growth factor (EGF) have the potential to improve ligament healing. Gene therapy approaches may represent a new alternative in delivering these specific growth factors to the ACL. The aim of this study was to investigate the feasibility of three different gene therapy approaches (direct-, fibroblast-, and myoblast-mediated gene transfer) to the ACL. Rabbit myoblasts and ACL-fibroblasts were transduced with 5 x 10(7) recombinant adenoviral particles carrying the LacZ reporter gene (MOI = 50). Myoblasts and fibroblasts (1 x 10(6)) were each injected into the right ACL of 10 adult rabbits; direct injection of 5 x 10(7) adenoviral particles was performed in 10 other rabbits. The left side was used as sham. The beta-galactosidase production was revealed using the LacZ histochemical technique. The transduced fibroblasts and myoblasts were found in the ligament tissue and in the synovial tissue surrounding the ACL at 4, 7, 14, and 21 days postinjection. The myoblasts fused and formed myotubes in the ligament. The direct approach also allowed the transfer of the marker gene in the ligament at 4, 7, 21, and 42 days postinjection. X-gal staining revealed no expression of beta-galactosidase in the sham ligament. The presence of cells expressing the marker gene in the ACL opens up the possibility of delivering proteins (i.e., PDGF, TGF-beta, and EGF) capable of improving ACL healing and graft maturation. Furthermore, engineered myoblasts may mediate and accelerate the intraligament neovascularization. This new technology based on gene therapy and tissue engineering may allow a persistent expression of selected growth factors to enhance ACL healing following injury.

  • Adenoviridae/genetics
  • Animals
  • Anterior Cruciate Ligament/cytology/injuries/metabolism
  • Artificial Organs
  • Cell Transplantation
  • Defective Viruses/genetics
  • Feasibility Studies
  • Fibroblasts/metabolism/transplantation
  • Gene Transfer Techniques
  • Genes, Reporter
  • Genetic Vectors/genetics
  • Lac Operon
  • Muscle, Skeletal/cytology/metabolism
  • Neovascularization, Physiologic
  • Rabbits
  • Recombinant Fusion Proteins/biosynthesis
  • Time Factors
  • Wound Healing
  • Beta-Galactosidase/biosynthesis/genetics
Citation (ISO format)
MENETREY, Jacques et al. Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament. In: Tissue engineering, 1999, vol. 5, n° 5, p. 435–442.
Main files (1)
Article (Published version)
ISSN of the journal1076-3279

Technical informations

Creation06/02/2015 11:41:00 AM
First validation06/02/2015 11:41:00 AM
Update time03/14/2023 11:20:53 PM
Status update03/14/2023 11:20:52 PM
Last indexation10/18/2023 11:04:24 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack