首页> 外文期刊>Journal of Molecular Biochemistry >Overexpression of human DKK1 via rAAV vector-mediated gene transfer stimulates chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells
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Overexpression of human DKK1 via rAAV vector-mediated gene transfer stimulates chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells

机译:通过rAAV载体介导的基因转移使人DKK1过表达刺激人骨髓间充质干细胞的软骨分化

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Enhancing the chondroregenerative activities of mesenchymal stem cells via therapeutic gene transfer as reinforced sources of implantable cells in sites of cartilage injury is a promising tool to improve the natural processes of cartilage repair. In the present study, we show that overexpression of the Dickkopf-related protein 1 (DKK1) via clinically adapted recombinant adeno-associated viral (rAAV) vectors is capable of significantly stimulating proliferative, anabolic, and chondrodifferentiation events in primary human mesenchymal stem cells compared with control (reporter rAAV lacZ) transduction over an extended period of time in vitro (21 days). Strikingly, administration of the rAAV DKK1 candidate vector concomitantly restrained unwanted osteogenic and hypertrophic differentiation outcomes in these cells. These findings reveal the possible future benefits of such an approach to treat articular cartilage lesions in relevant experimental models in vivo.
机译:通过治疗性基因转移增强间充质干细胞的软骨再生活性,作为软骨损伤部位可植入细胞的增强来源,是改善软骨修复自然过程的有前途的工具。在本研究中,我们显示,通过临床适应的重组腺相关病毒(rAAV)载体,Dickkopf相关蛋白1(DKK1)的过表达能够显着刺激人间充质干细胞中的增殖,合成代谢和软骨分化事件。在延长的时间内(21天)进行对照(reporter rAAV lacZ)的转导。令人惊讶地,施用rAAV DKK1候选载体同时抑制了这些细胞中不需要的成骨和肥大性分化结果。这些发现揭示了这种在体内相关实验模型中治疗关节软骨病变的方法可能带来的未来益处。

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