Effects of transforming growth factor-beta1 and vascular endothelial growth factor 165 gene transfer on Achilles tendon healing

Matrix Biol. 2009 Jul;28(6):324-35. doi: 10.1016/j.matbio.2009.04.007. Epub 2009 Apr 21.

Abstract

Repaired Achilles tendons typically take weeks before they are strong enough to handle physiological loads. Gene therapy is a promising treatment for Achilles tendon defects. The aim of the present study was to evaluate the histological/biomechanical effects of Transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor 165 (VEGF(165)) gene transfer on Achilles tendon healing in rabbits. Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) were transduced with adenovirus carrying human TGF-beta1 cDNA (Ad-TGF-beta1), human VEGF(165) cDNA (Ad-VEGF(165)), or both (PIRES-TGF-beta1/VEGF(165)) Viruses, no cDNA (Ad-GFP), and the BMSCs without gene transfer and the intact tendon were used as control. BMSCs were surgically implanted into the experimentally injured Achilles tendons. TGF-beta1 distribution, cellularity, nuclear aspect ratio, nuclear orientation angle, vascular number, collagen synthesis, and biomechanical features were measured at 1, 2, 4, and 8 weeks after surgery. The TGF-beta1 and TGF beta 1/VEGF(165) co-expression groups exhibited improved parameters compared with other groups, while the VEGF(165) expression group had a negative impact. In the co-expression group, the angiogenesis effects of VEGF(165) were diminished by TGF-beta1, while the collagen synthesis effects of TGF-beta1 were unaltered by VEGF(165). Thus treatment with TGF-beta1 cDNA-transduced BMSCs grafts is a promising therapy for acceleration and improvement of tendon healing, leading to quicker recovery and improved biomechanical properties of Achilles tendons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / anatomy & histology
  • Achilles Tendon / physiology*
  • Animals
  • Biomechanical Phenomena
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology
  • Rabbits
  • Regeneration / physiology*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Transforming Growth Factor beta1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A