Enhanced Achilles tendon healing by fibromodulin gene transfer

被引:46
作者
Delalande, Anthony [1 ]
Gosselin, Marie-Pierre [1 ]
Suwalski, Arnaud [1 ]
Guilmain, William [1 ]
Leduc, Chloe [1 ]
Berchel, Mathieu [2 ]
Jaffres, Paul-Alain [2 ]
Baril, Patrick [1 ]
Midoux, Patrick [1 ]
Pichon, Chantal [1 ]
机构
[1] Ctr Biophys Mol, Orleans 2, France
[2] Univ Brest, Univ Europeenne Bretagne, ScInBioS IFR148, CEMCA,CNRS UMR 6521, Brest, France
关键词
Tendon healing; Gene therapy; Lipoplex; Polyplex; DIFFERENTIAL EXPRESSION; GROWTH-FACTORS; IN-VITRO; PDGF; DELIVERY; LUMICAN; LIGAMENT;
D O I
10.1016/j.nano.2015.05.004
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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 liposomalbased 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. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:1735 / 1744
页数:10
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