具有 GLRX3+ 细胞外囊泡的氧化还原稳态调节水凝胶通过抑制髓核细胞衰老来减轻椎间盘退变,ACS Nano

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具有 GLRX3+ 细胞外囊泡的氧化还原稳态调节水凝胶通过抑制髓核细胞衰老来减轻椎间盘退变
ACS Nano ( IF 15.8 ) Pub Date : 2023-07-11 , DOI: 10.1021/acsnano.3c01713
Can Liu ₁ , Lei Fan ₂ , Ming Guan ₁ , Qiangqiang Zheng ₃ , Jiale Jin ₁ , Xinchang Kang ₄ , Zhongyang Gao ₁ , Xiaoqian Deng ₅ , Yifan Shen ₁ , Guangyu Chu ₁ , Jingyao Chen ₆ , Zhiqiang Yu ₇ , Lei Zhou ₈ , Yue Wang ₁

Affiliation

椎间盘退变以髓核（NP）细胞衰老和细胞外基质（ECM）退化为特征，是各种退行性脊柱疾病的常见病理。迄今为止，还缺乏针对椎间盘退变的有效治疗方法。在这里，我们发现谷氧还蛋白3（GLRX3）是一种与NP细胞衰老和椎间盘退变相关的重要氧化还原调节分子。采用低氧预处理方法，我们开发了GLRX3 ⁺间充质干细胞衍生的细胞外载体（EVs-GLRX3），它增强了细胞抗氧化防御，从而防止活性氧（ROS）积累和体外衰老级联扩张。此外，还提出了一种基于椎间盘组织的生物聚合物超分子水凝胶，该水凝胶可注射、可降解且具有 ROS 响应性，可提供 EVs-GLRX3 来治疗椎间盘退变。使用大鼠椎间盘退变模型，我们证明负载 EVs-GLRX3 的水凝胶可减轻线粒体损伤，减轻 NP 衰老状态，并通过调节氧化还原稳态来恢复 ECM 沉积。我们的研究结果表明，调节椎间盘氧化还原稳态可以使 NP 细胞衰老恢复活力，从而减轻椎间盘退变。

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A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3⁺ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.

更新日期：2023-07-11

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