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丁香酚预处理间充质干细胞衍生的细胞外囊泡促进肌腱干细胞的抗氧化能力。

Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells and .

机构信息

Department of General Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Orthopaedics, Heilongjiang Red Cross Sengong General Hospital, Heilongjiang, China.

出版信息

Oxid Med Cell Longev. 2022 Feb 8;2022:3945195. doi: 10.1155/2022/3945195. eCollection 2022.

DOI:10.1155/2022/3945195
PMID:35178155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8847013/
Abstract

Tendon stem cells (TSCs) are often exposed to oxidative stress at tendon injury sites, which impairs their physiological effect as well as therapeutic application. Recently, extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) were shown to mediate cell protection and survival under stress conditions. The function of BMSC-EVs may be affected by pretreatment with various factors such as eugenol (EUG)-a powerful antioxidant. In our previous study, we found that HO significantly impaired TSC proliferation and tenogenic differentiation capabilities. Apoptosis and intracellular ROS accumulation in TSCs were induced by HO. However, such HO-induced damage was prevented by treatment with EUG-BMSC-EVs. Furthermore, EUG-BMSC-EVs activated the Nrf2/HO-1 pathway to counteract HO-induced damage in TSCs. In a rat patellar tendon injury model, the ROS level was significantly higher than that in the normal tendon and TSCs not pretreated showed a poor therapeutic effect. However, EUG-BMSC-EV-pretreated TSCs significantly improved tenogenesis and matrix regeneration during tendon healing. Additionally, the EUG-BMSC-EV group had a significantly improved fiber arrangement. Overall, EUG-BMSC-EVs protected TSCs against oxidative stress and enhanced their functions in tendon injury. These findings provide a basis for potential clinical use of EUG-BMSC-EVs as a new therapeutic vehicle to facilitate TSC therapies for tendon regeneration.

摘要

肌腱干细胞 (TSC) 在肌腱损伤部位经常受到氧化应激的影响，这会损害它们的生理作用和治疗应用。最近，骨髓间充质干细胞 (BMSC) 衍生的细胞外囊泡 (EV) 被证明可以在应激条件下介导细胞保护和存活。BMSC-EV 的功能可能受到各种因素的预处理的影响，如丁香酚 (EUG)-一种强大的抗氧化剂。在我们之前的研究中，我们发现 HO 显著损害了 TSC 的增殖和肌腱分化能力。HO 诱导 TSCs 凋亡和细胞内 ROS 积累。然而，EUG-BMSC-EV 处理可预防 HO 诱导的 TSC 损伤。此外，EUG-BMSC-EV 激活了 Nrf2/HO-1 通路，以抵抗 HO 诱导的 TSC 损伤。在大鼠髌腱损伤模型中，ROS 水平明显高于正常肌腱，未经预处理的 TSCs 表现出较差的治疗效果。然而，EUG-BMSC-EV 预处理的 TSCs 显著改善了腱愈合过程中的肌腱生成和基质再生。此外，EUG-BMSC-EV 组的纤维排列得到了明显改善。总的来说，EUG-BMSC-EVs 保护 TSCs 免受氧化应激，并增强了它们在肌腱损伤中的功能。这些发现为 EUG-BMSC-EVs 作为一种新的治疗载体促进 TSC 治疗肌腱再生的潜在临床应用提供了依据。

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