Modification of mesenchymal stromal cells with silibinin-loaded PLGA nanoparticles improves their therapeutic efficacy for cutaneous wound repair

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Ningfei Shen MSc , Anna Polyanskaya MSc , Xiaoli Qi PhD , Aya Al Othman MSc , Anastasia Permyakova PhD , Marina Volkova PhD , Alexandre Mezentsev PhD , Mikhail Durymanov PhD
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Abstract

The use of mesenchymal stromal cells (MSCs) for treating chronic inflammatory disorders, wounds, and ischemia-reperfusion injuries has shown improved healing efficacy. However, the poor survival rate of transplanted cells due to oxidative stress in injured or inflamed tissue remains a significant concern for MSC-based therapies. In this study, we developed a new approach to protect MSCs from oxidative stress, thereby improving their survival in a wound microenvironment and enhancing their therapeutic effect. We produced PLGA nanoparticles loaded with the cytoprotective phytochemical silibinin (SBN), and used them to modify MSCs. Upon internalization, these nanoformulations released SBN, activating the Nrf2/ARE signaling pathway, resulting in threefold reduction in intracellular ROS content and improved cell survival under oxidative stress conditions. Modification of MSCs with SBN-loaded PLGA nanoparticles increased their survival upon transplantation to full-thickness cutaneous wounds and improved wound healing. This study suggests that MSC modification with cytoprotective nanoparticles could be a promising approach for improving wound healing.

Abstract Image

用含有 Silibinin 的 PLGA 纳米颗粒修饰间充质基质细胞,提高其对皮肤伤口修复的疗效。
使用间充质基质细胞(MSCs)治疗慢性炎症性疾病、伤口和缺血再灌注损伤已显示出较好的疗效。然而,由于受伤或发炎组织中的氧化应激,移植细胞的存活率很低,这仍然是基于间充质干细胞疗法的一个重大问题。在本研究中,我们开发了一种新方法来保护间充质干细胞免受氧化应激,从而提高其在伤口微环境中的存活率并增强其治疗效果。我们制备了负载有细胞保护作用的植物化学物质 Silibinin(SBN)的 PLGA 纳米颗粒,并用它们来修饰间充质干细胞。在内化过程中,这些纳米制剂释放出 SBN,激活了 Nrf2/ARE 信号通路,从而使细胞内 ROS 含量降低了三倍,提高了细胞在氧化应激条件下的存活率。用SBN负载的PLGA纳米颗粒修饰间充质干细胞,可提高其移植到全厚皮肤伤口后的存活率,并改善伤口愈合。这项研究表明,用具有细胞保护作用的纳米颗粒修饰间充质干细胞是一种很有前景的改善伤口愈合的方法。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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