Selenized neural stem cell-derived exosomes: A neotype therapeutic agent for traumatic injuries of the central nervous system.

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-08-28 DOI:10.1016/j.xcrm.2025.102319

Wenjing Wang, Guihong Lu, Peilin Guo, Haochong Zhang, Yan Wang, Diwei Zheng, Chengliang Lyu, Dongfang Wang, Shang Li, Feng Li, Jiawei Zhao, Meng Qin, Weiping Li, Hui Tan, Guanghui Ma, Wei Wei

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引用次数: 0

Abstract

Oxidative damage and neuroinflammation are the key features of central nervous system (CNS) injury. Inspired by the neuroprotective properties of neural stem cell-derived exosomes (NExo) and the reactive oxygen species (ROS) scavenging ability of selenium, we develop an advanced NExo bearing ultrasmall nano-selenium (∼3.5 nm) via lipid-mediated nucleation (SeNExo). In addition to maintaining the biological components of NExo, the resulting SeNExo exhibits a Se-O bond that dramatically enhances its ROS-scavenging performance. SeNExo penetrates the blood-brain barrier (BBB) via the apolipoprotein E and prolow-density lipoprotein receptor-related protein 1 (APOE_LRP-1) interaction. Through proteomics, microRNA (miRNA) omics, and single-nucleus RNA sequencing, we find that SeNExo can alleviate neuronal apoptosis, restore glia homeostasis, and remodel glia-neuron networks. Therefore, SeNExo confers potent therapeutic benefits, significantly reducing cerebral lesions in a murine traumatic brain injury model. Even extending to a murine spinal cord injury model, SeNExo promotes locomotory recovery, further supporting SeNExo as a neotype and a promising therapeutic agent for treating traumatic CNS injury.

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硒化神经干细胞源性外泌体：一种新型中枢神经系统创伤性损伤治疗剂。

氧化损伤和神经炎症是中枢神经系统（CNS）损伤的主要特征。受神经干细胞衍生外泌体（NExo）的神经保护特性和硒的活性氧（ROS）清除能力的启发，我们通过脂质介导成核（SeNExo）开发了一种先进的NExo承载超小纳米硒（~ 3.5 nm）。除了维持NExo的生物成分外，所得到的SeNExo还具有Se-O键，可显着提高其清除ros的性能。SeNExo通过载脂蛋白E和前密度脂蛋白受体相关蛋白1 （APOE_LRP-1）相互作用穿透血脑屏障（BBB）。通过蛋白质组学、microRNA （miRNA）组学和单核RNA测序，我们发现SeNExo可以缓解神经元凋亡，恢复胶质细胞稳态，重塑胶质神经元网络。因此，SeNExo具有有效的治疗效果，可显著减少小鼠创伤性脑损伤模型中的脑病变。甚至扩展到小鼠脊髓损伤模型，SeNExo促进运动恢复，进一步支持SeNExo作为一种新型和有前途的治疗创伤性中枢神经系统损伤的药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.