Enhanced Achilles tendon healing by fibromodulin gene transfer

Nanomedicine. 2015 Oct;11(7):1735-44. doi: 10.1016/j.nano.2015.05.004. Epub 2015 Jun 3.

Abstract

Tendon injury is a major musculoskeletal disorder with a high public health impact. We propose a non-viral based strategy of gene therapy for the treatment of tendon injuries using histidylated vectors. Gene delivery of fibromodulin, a proteoglycan involved in collagen assembly was found to promote rat Achilles tendon repair in vivo and in vitro. In vivo liposome-based transfection of fibromodulin led to a better healing after surgical injury, biomechanical properties were better restored compared to untransfected control. These measures were confirmed by histological observations and scoring. To get better understandings of the mechanisms underlying fibromodulin transfection, an in vitro tendon healing model was developed. In vitro, polymer-based transfection of fibromodulin led to the best wound enclosure speed and a pronounced migration of tenocytes primary cultures was observed. These results suggest that fibromodulin non-viral gene therapy could be proposed as a new therapeutic strategy to accelerate tendon healing.

From the clinical editor: Tendon injury is relatively common and healing remains unsatisfactory. In this study, the effects of liposomal-based delivery of fibromodulin gene were investigated in a rat Achilles tendon injury model. The positive results observed would provide a new therapeutic strategy in clinical setting in the future.

Keywords: Gene therapy; Lipoplex; Polyplex; Tendon healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / pathology
  • Adenoviridae / genetics
  • Animals
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics*
  • Fibromodulin
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Liposomes / chemistry
  • Male
  • Proteoglycans / biosynthesis
  • Proteoglycans / genetics*
  • Rats
  • Tendon Injuries / genetics
  • Tendon Injuries / pathology
  • Tendon Injuries / therapy*
  • Wound Healing / genetics

Substances

  • Extracellular Matrix Proteins
  • FMOD protein, human
  • Fmod protein, rat
  • Liposomes
  • Proteoglycans
  • Fibromodulin