Extracellular vesicles containing upregulated HSP70 from heat shock pretreated human umbilical cord mesenchymal stem cells ameliorates sleep deprivation induced anxiety-like behavior and cognitive impairment in mice

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy-Methods & Clinical Development Pub Date : 2024-02-05 DOI:10.1016/j.omtm.2024.101207

Yiqin Lin, Zhenming Kang, Changsheng Su, Shunyuan Li, Wenqin Xie

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Abstract

The aim of this research was to explore the therapeutic capabilities of extracellular vehicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) that had been subjected to heat shock pretreatment, in treating psychiatric disorders induced by sleep deprivation in mice. The EVs were isolated and characterized, while Western blotting was utilized to assess the expression of exosomal markers and heat shock protein 70 (HSP70). To evaluate the impact of EV treatment on anxiety-like behavior and cognitive impairment in sleep-deprived (SD) mice, open field test, plus maze test and Y-maze task were conducted. Heat shock pretreatment significantly increased the expression of HSP70 in EVs. Administration of EVs from heat shock pretreated hUC-MSCs improved anxiety-like behavior and cognitive function in sleep-deprived mice. Furthermore, EV treatment promoted synaptic protein expression, HSP70 expression and inhibited neuroinflammation in the hippocampus of SD mice. Western blotting analysis also revealed that EV treatment reduced the levels of TLR4 and p65 in the hippocampus. EVs from heat shock-pretreated hUC-MSCs have therapeutic potential for sleep deprivation-induced psychiatric disorders by regulating neuroinflammation and synaptic function in mice.

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来自热休克预处理人脐带间充质干细胞的细胞外囊泡含有上调的 HSP70，可改善睡眠剥夺诱发的小鼠焦虑样行为和认知障碍

本研究的目的是探索从经过热休克预处理的人脐带间充质干细胞（hUC-MSCs）中提取的细胞外载体（EVs）在治疗小鼠睡眠剥夺诱发的精神障碍方面的治疗能力。对EVs进行了分离和鉴定，并利用Western印迹法评估了外泌体标记物和热休克蛋白70（HSP70）的表达。为了评估EV处理对睡眠剥夺（SD）小鼠焦虑样行为和认知障碍的影响，研究人员进行了开阔地测试、正迷宫测试和Y迷宫任务。热休克预处理明显增加了EVs中HSP70的表达。给予经热休克预处理的hUC-间充质干细胞的EVs能改善睡眠不足小鼠的焦虑样行为和认知功能。此外，EV 处理促进了 SD 小鼠海马中突触蛋白的表达和 HSP70 的表达，并抑制了神经炎症。Western 印迹分析还显示，EV 处理降低了海马中 TLR4 和 p65 的水平。经热休克预处理的hUC-间充质干细胞的EV可调节小鼠的神经炎症和突触功能，对睡眠剥夺诱发的精神疾病具有治疗潜力。

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来源期刊

Molecular Therapy-Methods & Clinical Development Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.90

自引率

4.30%

发文量

163

审稿时长

12 weeks

期刊介绍： The aim of Molecular Therapy—Methods & Clinical Development is to build upon the success of Molecular Therapy in publishing important peer-reviewed methods and procedures, as well as translational advances in the broad array of fields under the molecular therapy umbrella. Topics of particular interest within the journal''s scope include: Gene vector engineering and production, Methods for targeted genome editing and engineering, Methods and technology development for cell reprogramming and directed differentiation of pluripotent cells, Methods for gene and cell vector delivery, Development of biomaterials and nanoparticles for applications in gene and cell therapy and regenerative medicine, Analysis of gene and cell vector biodistribution and tracking, Pharmacology/toxicology studies of new and next-generation vectors, Methods for cell isolation, engineering, culture, expansion, and transplantation, Cell processing, storage, and banking for therapeutic application, Preclinical and QC/QA assay development, Translational and clinical scale-up and Good Manufacturing procedures and process development, Clinical protocol development, Computational and bioinformatic methods for analysis, modeling, or visualization of biological data, Negotiating the regulatory approval process and obtaining such approval for clinical trials.