Enhanced Achilles tendon healing by fibromodulin gene transfer

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 EditorTendon 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.

Gene transfer by histidylated vectors of fibromodulin, a proteoglycan involved in collagen fibrillogenesis, was found to enhance wound healing on a rat Achilles tendon injury model. Fourteen days after the treatment, biomechanical and histological parameters showed a healing improvement compared to the non-treated tendons. In vitro wound healing and chemotaxis assays revealed that this effect is ascribed to an induction of cell migration. In summary, fibromodulin non-viral gene therapy could be a promising new therapeutic strategy for tendon healing.Figure optionsDownload high-quality image (199 K)Download as PowerPoint slide