Magnetofection of miR-21 promoted by electromagnetic field and iron oxide nanoparticles via the p38 MAPK pathway contributes to osteogenesis and angiogenesis for intervertebral fusion.
Magnetofection of miR-21 promoted by electromagnetic field and iron oxide nanoparticles via the p38 MAPK pathway contributes to osteogenesis and angiogenesis for intervertebral fusion.
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电磁场和氧化铁纳米粒子通过 p38 MAPK 途径促进 miR-21 的磁转染有助于椎间融合的骨生成和血管生成
DOI：
10.1186/s12951-023-01789-3
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发表时间：
2023-01-25
影响因子：
10.2
通讯作者：
Liu, Yang
中科院分区：
文献类型：
--
作者：
Wang, Tianqi;Zhao, Hongqi;Jing, Shaoze;Fan, Yang;Sheng, Gaohong;Ding, Qing;Liu, Chaoxu;Wu, Hua;Liu, Yang
磁转染介导的基因递送通过调节分化的方向和程度显示出巨大的治疗潜力。腰椎间盘退行性疾病是一个严重的全球性骨科问题。然而，尽管椎间融合术是治疗DDD的金标准，但其治疗效果并不令人满意。在这里，我们描述了一种新的磁转染系统，用于递送治疗性miRNA，以促进腰椎DDD患者的骨生成和血管生成。电磁场（EMF）和氧化铁纳米粒子（IONP）的共刺激显着提高磁转染效率。此外，在体外，将miR-21磁转染到骨髓间充质干细胞（BMSC）和人脐内皮细胞（HUVECs）中影响其细胞行为并促进骨生成和血管生成。然后，将基因编辑的种子细胞种植到聚己内酯（PCL）和羟基磷灰石（HA）支架（PCL/HA支架）上，并进化成理想的组织工程骨，以促进椎间融合。最后，我们的结果表明，EMF和聚乙烯亚胺（PEI）@ IONP通过激活p38 MAPK途径提高转染效率。我们的研究结果表明，用于将miR-21递送到BMSC和HUVECs中的磁转染系统在体外和体内促进骨生成和血管生成，并且在EMF和IONP的共刺激下磁转染转染效率显著提高。此外，它依赖于p38 MAPK通路的激活。这种磁转染系统可能是一种有前途的治疗方法，对各种骨科疾病。
Magnetofection-mediated gene delivery shows great therapeutic potential through the regulation of the direction and degree of differentiation. Lumbar degenerative disc disease (DDD) is a serious global orthopaedic problem. However, even though intervertebral fusion is the gold standard for the treatment of DDD, its therapeutic effect is unsatisfactory. Here, we described a novel magnetofection system for delivering therapeutic miRNAs to promote osteogenesis and angiogenesis in patients with lumbar DDD. Co-stimulation with electromagnetic field (EMF) and iron oxide nanoparticles (IONPs) enhanced magnetofection efficiency significantly. Moreover, in vitro, magnetofection of miR-21 into bone marrow mesenchymal stem cells (BMSCs) and human umbilical endothelial cells (HUVECs) influenced their cellular behaviour and promoted osteogenesis and angiogenesis. Then, gene-edited seed cells were planted onto polycaprolactone (PCL) and hydroxyapatite (HA) scaffolds (PCL/HA scaffolds) and evolved into the ideal tissue-engineered bone to promote intervertebral fusion. Finally, our results showed that EMF and polyethyleneimine (PEI)@IONPs were enhancing transfection efficiency by activating the p38 MAPK pathway. Our findings illustrate that a magnetofection system for delivering miR-21 into BMSCs and HUVECs promoted osteogenesis and angiogenesis in vitro and in vivo and that magnetofection transfection efficiency improved significantly under the co-stimulation of EMF and IONPs. Moreover, it relied on the activation of p38 MAPK pathway. This magnetofection system could be a promising therapeutic approach for various orthopaedic diseases.
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影响因子：
4.8
作者：
Hatakeyama, J;Kageyama, R
通讯作者：
Kageyama, R
影响因子：
9.7
作者：
Gwak SJ;Nice J;Zhang J;Green B;Macks C;Bae S;Webb K;Lee JS
通讯作者：
Lee JS
影响因子：
5.1
作者：
Jackson KL;Dayton RD;Orchard EA;Ju S;Ringe D;Petsko GA;Maquat LE;Klein RL
通讯作者：
Klein RL
影响因子：
9
作者：
Celik, Nazmiye;Kim, Myoung Hwan;Yeo, Miji;Kamal, Fadia;Hayes, Daniel J.;Ozbolat, Ibrahim T.
通讯作者：
Ozbolat, Ibrahim T.
影响因子：
3.1
作者：
Barbieri, D.;Renard, A. J. S.;Yuan, H.
通讯作者：
Yuan, H.