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首页> 外文期刊>Polymers for advanced technologies >Ultrasound-mediated transgene expression in endogenous stem cells recruited to bone injury sites
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Ultrasound-mediated transgene expression in endogenous stem cells recruited to bone injury sites

机译：超声介导的转基因在募集到骨损伤部位的内源性干细胞中的表达

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When fractured, bone can spontaneously heal to a certain extent. In critical-size defects, in which bone loss is severe, a bone graft is required. Faced with the shortcomings of grafts currently in use-autografts, allografts, and mineral-based bone substitutes-efforts are being made to establish new methods of bone regeneration. One promising approach involves the use of exogenous gene-modified mesenchymal stem cells (MSCs), which can rapidly repair large bone defects in animal models. Unfortunately, ex vivo culture of MSCs may add certain complexity to the advancement of this cell therapy to the clinic. Previously, we demonstrated efficient bone regeneration following direct gene delivery to endogenous MSCs that had been attracted to a fracture site. In that study, electroporation was used, but it is an invasive method of gene transfection that may result in tissue damage. Unlike electroporation, sonoporation-the use of ultrasound for gene delivery-is noninvasive, considered safer, and relevant to the clinical setting. In this study, we evaluated the feasibility of ultrasound-based gene delivery to resident MSCs that had been recruited to a fracture site in different animal models. Our results show transient (up to 21 days) expression of a reporter gene in radial, vertebral, and tibial bone defects in mice, rats, and a minipig. These results could prove beneficial for the next phase of experiments, in which osteogenic genes such as the bone morphogentic proteins (BMPs) could be utilized to achieve bone regeneration in similar challenging conditions of bone tissue loss.
机译：骨折时，骨骼可以自发愈合到一定程度。在骨丢失严重的临界尺寸缺损中，需要植骨。面对目前使用中的移植物的缺点，自体移植物，同种异体移植物和矿物基骨替代物正在努力建立新的骨再生方法。一种有前途的方法涉及使用外源基因修饰的间充质干细胞（MSC），它可以快速修复动物模型中的大骨缺损。不幸的是，MSC的离体培养可能增加这种细胞疗法进入临床的复杂度。以前，我们证明了将基因直接传递到已吸引到骨折部位的内源MSC后的有效骨再生。在该研究中，使用了电穿孔，但这是一种基因转染的侵入性方法，可能导致组织损伤。与电穿孔不同，声穿孔-使用超声波进行基因递送-是非侵入性的，被认为更安全，并且与临床环境有关。在这项研究中，我们评估了将基于超声波的基因递送至已被募集到不同动物模型中的骨折部位的常驻MSC的可行性。我们的结果表明，在小鼠，大鼠和小型猪的radial骨，椎骨和胫骨缺损中，报告基因瞬时表达（最多21天）。这些结果可能证明对下一阶段的实验有益，在该阶段中，可以利用成骨基因（例如骨形态发生蛋白（BMP））在相似的骨组织丧失挑战性条件下实现骨再生。

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