Induced Mesenchymal Stem Cells-Small Extracellular Vesicles Alleviate Post-stroke Cognitive Impairment by Rejuvenating Senescence of Neural Stem Cells

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2024-03-13 DOI:10.1007/s12031-024-02191-w

Jiayuan Liu, Li Peng, Lingwei He, Tianyue Yin, Yuhao Du, Mengmeng Yang, Ping Wu, Jun Li, Jiangbing Cao, Hongrui Zhu, Sheng Wang

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Abstract

Ischemic stroke is typified by hypoxia and a cascade of pathophysiological events, including metabolic dysfunction, ionic dysregulation, excitotoxicity, inflammatory infiltration, and oxidative stress. These ultimately result in neuronal apoptosis or necrosis with constrained neuroregenerative capabilities. In this study, neural stem cells (NSCs) under conditions of oxygen–glucose deprivation (OGD) in vitro and following middle cerebral artery occlusion (MCAO) in vivo were explored. Transcriptome sequencing revealed a decline in NSC differentiation and neurogenesis after OGD exposure, which was related to cellular senescence. This observation was corroborated by increased senescence markers in the MCAO mouse model, reduction in NSC numbers, and decline in neurogenesis. Importantly, iMSC-sEVs (induced mesenchymal stem cells-small extracellular vesicles) have the therapeutic potential to alleviate NSC senescence and rejuvenate their regenerative capacities both in vitro and in vivo. Moreover, iMSC-sEVs contribute to the recovery of cognitive function and synapse loss caused by MCAO.

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诱导间充质干细胞-细胞外小泡通过使衰老的神经干细胞年轻化来缓解中风后的认知障碍

缺血性中风的典型特征是缺氧和一系列病理生理事件，包括代谢功能障碍、离子失调、兴奋毒性、炎症浸润和氧化应激。这些最终导致神经元凋亡或坏死，神经再生能力受到限制。本研究探讨了体外氧-葡萄糖剥夺（OGD）条件下和体内大脑中动脉闭塞（MCAO）后的神经干细胞（NSCs）。转录组测序显示，OGD暴露后，NSC分化和神经发生能力下降，这与细胞衰老有关。MCAO 小鼠模型中衰老标志物的增加、NSC 数量的减少和神经发生的下降证实了这一观察结果。重要的是，iMSC-sEVs（诱导间充质干细胞-细胞外小泡）具有缓解NSC衰老和恢复其体内外再生能力的治疗潜力。此外，iMSC-sEVs 还有助于恢复 MCAO 引起的认知功能和突触丧失。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.