title: Enhanced Achilles tendon healing by fibromodulin gene transfer.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Delalande
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gosselin
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Suwalski
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: William
authors.initials: W
authors.lastname: Guilmain
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Leduc
authors.affiliation: CEMCA, CNRS UMR 6521, IFR148 ScInBioS, Université Européenne de Bretagne, Université de Brest, Brest, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Berchel
authors.affiliation: CEMCA, CNRS UMR 6521, IFR148 ScInBioS, Université Européenne de Bretagne, Université de Brest, Brest, France.
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffrès
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Baril
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Midoux
authors.affiliation: Centre de Biophysique Moléculaire, rue Charles Sadron, Orléans CEDEX 2, France. Electronic address: chantal.pichon@cnrs-orleans.fr.
authors.forename: Chantal
authors.initials: C
authors.lastname: Pichon
mesh_terms: D000125:Achilles Tendon / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D000071235:Fibromodulin; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D013708:Tendon Injuries / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014945:Wound Healing / Q000235:genetics
chemical_list: D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604334:Fmod protein, rat; D008081:Liposomes; D011509:Proteoglycans; D000071235:Fibromodulin
keywords: Gene therapy; Lipoplex; Polyplex; Tendon healing