Gene-activated engineered exosome directs osteoblastic differentiation of progenitor cells and induces vascularized osteogenesis in situ
Gene-activated engineered exosome directs osteoblastic differentiation of progenitor cells and induces vascularized osteogenesis in situ
复制标题
基因激活的工程外泌体指导祖细胞的成骨细胞分化并原位诱导血管化成骨
DOI：
10.1016/j.cej.2020.125939
复制
发表时间：
2020-06
影响因子：
15.1
通讯作者：
Li Zubing
中科院分区：
文献类型：
--
作者：
Lin Tianyi;Zha Yao;Zhang Xin;Chen Jia;Li Yawu;Wang Zihao;Zhang Shengmin;Wang Jianglin;Li Zubing
外切体作为一种先进的载体，由于其良好的生物相容性、高效的细胞摄取和方便的靶向修饰，已被广泛应用于基因和药物的传递。除了传统的生物活性分子的控制释放外，一些其他的外切体作用还有待于进一步的研究。在此，我们报道了构建一种特异性的基因激活的工程化外切体，它不仅可以有效地调节血管内皮生长因子165(VEGF165)的基因释放，而且在促进血管骨再生的治疗中发挥关键作用。我们的研究结果表明，通过基于外切体的载体可以极大地提高VEGF165基因的转染率。单独的外切体和工程化的外切体在体外均表现出一定的前体细胞成骨分化作用。更重要的是，将VEGF165基因内化的工程化外体与电纺纳米纤维膜相结合，在体内评估大鼠临界大小的颅骨缺损模型后，在成骨和血管生成方面发挥了双重作用。因此，我们目前的工作创造了一种基于外切体的双功能工程生物材料，它可以在体外指导祖细胞分化，并在体内促进血管化的骨再生，将外切体的应用从简单的生物分子载体扩展到外切体增强的治疗。
Exosome as an advanced carrier has been extensively used in gene and drug delivery due to its excellent biocompatibility, efficient cell uptake and convenient targeted modification. Apart from the conventionally controlled release of bioactive molecules, some other exosome roles should be further explored. Herein, we report to construct a specifically gene-activated engineered exosome that not only can effectively modulate the gene release of the vascular endothelial growth factor 165 (VEGF165), but also can play a pivotal role in enhancing therapy in vascular bone regeneration. Our findings revealed that the transfection efficiency of the VEGF165 plasmid gene was extremely elevated via the exosome-based vector. Both alone exosomes and engineered exosomes exhibited a certain osteoblastic differentiation of precursor cells (MC3T3-E1) in vitro. More importantly, the engineered exosomes that internalized the VEGF165 gene combined with electrospun nanofiber films played a dual role in osteogenesis and angiogenesis based on the evaluation of a rat critical-sized calvarial defect model in vivo. Consequently, our current work creates a bifunctional engineered exosome-based biomaterial that can direct progenitor cell differentiation in vitro and promote the vascularized bone regeneration in vivo, extending exosome applications from simple biomolecular carriers to exosome-enhanced therapy.
登录
查看更多内容
影响因子：
14
作者：
Ho-Shui-Ling A;Bolander J;Rustom LE;Johnson AW;Luyten FP;Picart C
通讯作者：
Picart C
影响因子：
2
作者：
K. Ramachandran;P. Gouma
通讯作者：
K. Ramachandran;P. Gouma
影响因子：
8
作者：
Mendt, Mayela;Kamerkar, Sushrut;Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
10.8
作者：
Kim, Seung Min;Yang, Yoosoo;Jang, Mihue
通讯作者：
Jang, Mihue
影响因子：
4.1
作者：
Stegen, Steve;Carmeliet, Geert
通讯作者：
Carmeliet, Geert