Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

Sci Rep. 2016 Feb 11:6:20643. doi: 10.1038/srep20643.

Abstract

Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68-91% from week 2 after AAV2-bFGF treatment and by 82-210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Chickens
  • Collagen Type I / agonists
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Dependovirus / genetics*
  • Dependovirus / metabolism
  • Fibroblast Growth Factor 2 / agonists
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / metabolism
  • Fibronectins / agonists
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression Regulation
  • Genetic Therapy / methods
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Laminin / agonists
  • Laminin / genetics
  • Laminin / metabolism
  • Primary Cell Culture
  • Tendon Injuries / genetics
  • Tendon Injuries / metabolism
  • Tendon Injuries / pathology
  • Tendon Injuries / therapy*
  • Tendons / metabolism
  • Tendons / pathology
  • Tenocytes / cytology
  • Tenocytes / metabolism
  • Tensile Strength
  • Transgenes
  • Vascular Endothelial Growth Factor A / agonists
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / genetics*

Substances

  • Collagen Type I
  • Fibronectins
  • Laminin
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2