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通过金纳米棒递送赖氨酸特异性去甲基化酶1(LSD1)小干扰RNA可诱导人间充质干细胞分化。

Gold nanorod delivery of LSD1 siRNA induces human mesenchymal stem cell differentiation.

作者信息

Zhao Xiongfei, Huang Qianying, Jin Yiqiang

机构信息

R&D center, Shanghai Angecon Biotechnology Co., Ltd, 588 Qiangdai Road, Pudong District, Shanghai 201318, China.

R&D center, Shanghai Angecon Biotechnology Co., Ltd, 588 Qiangdai Road, Pudong District, Shanghai 201318, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2015 Sep;54:142-9. doi: 10.1016/j.msec.2015.05.013. Epub 2015 May 8.

Abstract

Over the past decade, theranostic nanoparticles with microsize and multifunctional ability have emerged as a new platform in biomedical field, such as cancer therapy, optical imaging and gene therapy. Gene therapy has been recently shown as a promising tool for tissue engineering as safe and effective nanotechnology-based delivery methods are developed. Controlling adhesion and differentiation of stem cells is critical for tissue regeneration. In this study, we have developed poly-sodium 4-styrenesulfonate (PSS) and poly-allylamine hydrochloride (PAH) coated AuNR-based nanocarriers, which are capable of delivering small interfering RNA (siRNA) against LSD1 to induce the differentiation of human mesenchymal stem cells. To further study the mechanism, we tested the stemness and differentiation genes and found that they have been changed with LSD1 down-regulation. In addition, with the hepatocyte growth factor (HGF), LSD1 siRNA delivery by AuNRs could promote the differentiation of the human mesenchymal stem cells (human MSCs) into a hepatocyte lineage in vitro. Our results suggest for the first time use of AuNRs as nanocarriers of delivery LSD1 siRNA to induce the differentiation of human MSCs into a hepatocyte lineage, and envision the potential application of nanotechnology in tissue remodeling (such as liver and bone) in vivo, eventually translating to clinical applications.

摘要

在过去十年中,具有微米尺寸和多功能能力的诊疗纳米颗粒已成为生物医学领域的一个新平台,如癌症治疗、光学成像和基因治疗。随着基于纳米技术的安全有效递送方法的发展,基因治疗最近已成为组织工程的一种有前途的工具。控制干细胞的黏附和分化对于组织再生至关重要。在本研究中,我们开发了聚对苯乙烯磺酸钠(PSS)和聚烯丙胺盐酸盐(PAH)包覆的基于金纳米棒的纳米载体,其能够递送针对赖氨酸特异性去甲基化酶1(LSD1)的小干扰RNA(siRNA)以诱导人间充质干细胞的分化。为了进一步研究其机制,我们检测了干性和分化基因,发现它们随着LSD1的下调而发生了变化。此外,借助肝细胞生长因子(HGF),通过金纳米棒递送LSD1 siRNA可在体外促进人间充质干细胞(人MSCs)向肝细胞谱系的分化。我们的结果首次表明使用金纳米棒作为递送LSD1 siRNA的纳米载体来诱导人MSCs向肝细胞谱系的分化,并设想了纳米技术在体内组织重塑(如肝脏和骨骼)中的潜在应用,最终转化为临床应用。

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