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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >A doxycycline inducible, adenoviral bone morphogenetic protein-2 gene delivery system to bone
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A doxycycline inducible, adenoviral bone morphogenetic protein-2 gene delivery system to bone

机译：一种强霉素诱导，腺病毒骨形态发生蛋白-2基因递送系统到骨骼

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We report the novel use of a tuneable, non-integrating viral gene delivery system to bone that can be combined with clinically approved biomaterials in an 'off-the-shelf' manner. Specifically, a doxycycline inducible Tet-on adenoviral vector (AdTetBMP-2) in combination with mesenchymal stromal cells (MSCs), fibrin and a biphasic calcium phosphate ceramic (MBCP (R)) was used to repair large bone defects in nude rats. Bone morphogenetic protein-2 (BMP-2) transgene expression could be effectively tuned by modification of the doxycycline concentration. The effect of adenoviral BMP-2 gene delivery upon bone healing was investigated in vivo in 4 mm critically sized, internally fixated, femoral defects. MSCs were transduced either by direct application of AdTetBMP-2 or by pre-coating MBCP granules with the virus. Radiological assessment scores post-mortem were significantly improved upon delivery of AdTetBMP-2. In AdTetBMP-2 groups, histological analysis revealed significantly more newly formed bone at the defect site compared with controls. Newly formed bone was vascularized and fully integrated with nascent tissue and implanted biomaterial. Improvement in healing outcome was achieved using both methods of vector delivery (direct application vs. pre-coating MCBP). Adenoviral delivery of BMP-2 enhanced bone regeneration achieved by the transplantation of MSCs, fibrin and MBCP in vivo. Importantly, our in vitro and in vivo data suggest that this can be achieved with relatively low (ng/ml) levels of the growth factor. Our model and novel gene delivery system may provide a powerful standardized tool for the optimization of growth factor delivery and release for the healing of large bone defects. Copyright (C) 2016 John Wiley & Sons, Ltd.
机译：我们报告了一种可调节、非整合的病毒基因传递系统在骨中的新用途，该系统可以与临床批准的生物材料以“现成”的方式结合。具体而言，多西环素诱导的Tet-on腺病毒载体（AdTetBMP-2）与间充质基质细胞（MSCs）、纤维蛋白和双相磷酸钙陶瓷（MBCP（R））联合用于修复裸鼠的大骨缺损。骨形态发生蛋白-2（BMP-2）转基因表达可以通过改变强力霉素的浓度进行有效调节。在体内研究了腺病毒BMP-2基因转染对4mm临界尺寸、内固定股骨缺损骨愈合的影响。通过直接应用AdTetBMP-2或用病毒预包被MBCP颗粒来转导MSC。分娩ADBMP-2后，验尸后的放射学评估分数显著提高。在AdTetBMP-2组中，组织学分析显示，与对照组相比，缺损部位新形成的骨明显增多。新生骨血管化，与新生组织和植入的生物材料完全融合。使用两种载体递送方法（直接施用与预涂覆MCBP）可改善愈合效果。腺病毒载体BMP-2增强了骨髓间充质干细胞、纤维蛋白和MBCP在体内移植后的骨再生。重要的是，我们的体外和体内数据表明，这可以通过相对较低（ng/ml）的生长因子水平来实现。我们的模型和新的基因传递系统可能为优化生长因子的传递和释放提供一个强大的标准化工具，以促进大骨缺损的愈合。版权所有（C）2016约翰威利父子有限公司。

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