Rapid DNA Repair in Mesenchymal Stem Cells and Bone Regeneration by Nanoparticle-Based Codelivery of Nrf2-mRNA and Dexamethasone

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2024-11-09 DOI:10.1021/acsnano.4c08939

Ji Sun Park, Hayoung Jeon, Yeeun Lee, Seo Young Cheon, Donghyun Lee, Seong Gi Lim, Heebeom Koo

{"title":"Rapid DNA Repair in Mesenchymal Stem Cells and Bone Regeneration by Nanoparticle-Based Codelivery of Nrf2-mRNA and Dexamethasone","authors":"Ji Sun Park, Hayoung Jeon, Yeeun Lee, Seo Young Cheon, Donghyun Lee, Seong Gi Lim, Heebeom Koo","doi":"10.1021/acsnano.4c08939","DOIUrl":null,"url":null,"abstract":"Directional differentiation is a key factor determining the result of stem cell therapy. Herein, we developed a polyethylenimine (PEI)-coated poly(lactic-<i>co</i>-glycolic) acid (PLGA) nanoparticle (mPDN) carrying both nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and dexamethasone (Dex) to human mesenchymal stem cells (hMSCs). The combination of Dex and Nrf2-mRNA delivered by mPDN promoted the osteogenic differentiation of hMSCs. In particular, Nrf2-mRNA rapidly reduced the DNA damage caused by ROS due to early and efficient gene expression at 3 h after treatment, which was not achieved in traditional pDNA systems. High and rapid transfection, effective ROS-scavenging effect, and protection of mitochondrial dynamics were observed in hMSCs after treatment with the resulting Nrf2-mPDN. Osteogenic differentiation was also observed in 3D pellets for up to 5 weeks. Finally, the effects of rapid DNA repair in hMSCs by Nrf2-mPDN and on in vivo bone regeneration were evaluated in a rat femoral bone defect model using CT. This study demonstrated the potential of an NP-based codelivery system and efficient transfection of mRNA at early stages in hMSCs for bone regeneration and stem cell therapy.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":null,"pages":null},"PeriodicalIF":15.8000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.4c08939","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Directional differentiation is a key factor determining the result of stem cell therapy. Herein, we developed a polyethylenimine (PEI)-coated poly(lactic-co-glycolic) acid (PLGA) nanoparticle (mPDN) carrying both nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and dexamethasone (Dex) to human mesenchymal stem cells (hMSCs). The combination of Dex and Nrf2-mRNA delivered by mPDN promoted the osteogenic differentiation of hMSCs. In particular, Nrf2-mRNA rapidly reduced the DNA damage caused by ROS due to early and efficient gene expression at 3 h after treatment, which was not achieved in traditional pDNA systems. High and rapid transfection, effective ROS-scavenging effect, and protection of mitochondrial dynamics were observed in hMSCs after treatment with the resulting Nrf2-mPDN. Osteogenic differentiation was also observed in 3D pellets for up to 5 weeks. Finally, the effects of rapid DNA repair in hMSCs by Nrf2-mPDN and on in vivo bone regeneration were evaluated in a rat femoral bone defect model using CT. This study demonstrated the potential of an NP-based codelivery system and efficient transfection of mRNA at early stages in hMSCs for bone regeneration and stem cell therapy.

Abstract Image

查看原文本刊更多论文

基于纳米颗粒的 Nrf2-mRNA 和地塞米松重塑递送技术：间充质干细胞中的快速 DNA 修复和骨再生

定向分化是决定干细胞治疗效果的关键因素。在此，我们开发了一种聚乙烯亚胺（PEI）包覆的聚（乳酸-共聚-乙醇酸）纳米颗粒（mPDN），它同时携带核因子红细胞2相关因子2（Nrf2）mRNA和地塞米松（Dex），用于人间质干细胞（hMSCs）。mPDN递送的Dex和Nrf2-mRNA组合促进了hMSCs的成骨分化。特别是，Nrf2-mRNA 能在处理后 3 h 内早期高效表达基因，从而迅速减少 ROS 对 DNA 的损伤，这是传统 pDNA 系统无法实现的。经 Nrf2-mPDN 处理后，在 hMSCs 中观察到了高度和快速的转染、有效的 ROS 清除效果以及线粒体动力学保护。在三维颗粒中还观察到了长达 5 周的成骨分化。最后，在大鼠股骨头缺损模型中使用 CT 评估了 Nrf2-mPDN 在 hMSCs 中快速修复 DNA 以及对体内骨再生的影响。这项研究证明了基于NP的密码递送系统和mRNA早期高效转染hMSCs在骨再生和干细胞治疗方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.