Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University, No. 161, West 5th Road, Xincheng District, Xi'an, 710003, P.R. China.
College of Medicine, Yan'an University, Yongxiang Road, Baota District, Yan'an, 716000, China.
Stem Cell Res Ther. 2024 Aug 13;15(1):255. doi: 10.1186/s13287-024-03879-x.
Hemorrhagic stroke is a devastating cerebrovascular event with a high rate of early mortality and long-term disability. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for neurological conditions, such as intracerebral hemorrhage (ICH), has garnered considerable interest, has garnered considerable interest, though their mechanisms of action remain poorly understood.
EVs were isolated from human umbilical cord MSCs, and SPECT/CT was used to track the Tc-labeled EVs in a mouse model of ICH. A series of comprehensive evaluations, including magnetic resonance imaging (MRI), histological study, RNA sequencing (RNA-Seq), or miRNA microarray, were performed to investigate the therapeutic action and mechanisms of MSC-EVs in both cellular and animal models of ICH.
Our findings show that intravenous injection of MSC-EVs exhibits a marked affinity for the ICH-affected brain regions and cortical neurons. EV infusion alleviates the pathological changes observed in MRI due to ICH and reduces damage to ipsilateral cortical neurons. RNA-Seq analysis reveals that EV treatment modulates key pathways involved in the neuronal system and metal ion transport in mice subjected to ICH. These data were supported by the attenuation of neuronal ferroptosis in neurons treated with Hemin and in ICH mice following EV therapy. Additionally, miRNA microarray analysis depicted the EV-miRNAs targeting genes associated with ferroptosis, and miR-214-3p was identified as a regulator of neuronal ferroptosis in the ICH cellular model.
MSC-EVs offer neuroprotective effects against ICH-induced neuronal damage by modulating ferroptosis highlighting their therapeutic potential for combating neuronal ferroptosis in brain disorders.
出血性中风是一种具有高早期死亡率和长期残疾率的破坏性脑血管事件。间充质干细胞衍生的细胞外囊泡（MSC-EVs）在治疗神经疾病方面具有巨大潜力，如脑出血（ICH），尽管其作用机制仍知之甚少。
从人脐带 MSC 中分离 EVs，并使用 SPECT/CT 追踪 Tc 标记的 EVs 在 ICH 小鼠模型中的分布。进行了一系列全面评估，包括磁共振成像（MRI）、组织学研究、RNA 测序（RNA-Seq）或 miRNA 微阵列，以研究 MSC-EVs 在 ICH 细胞和动物模型中的治疗作用和机制。
我们的研究结果表明，MSC-EVs 的静脉注射对 ICH 影响的大脑区域和皮质神经元具有明显的亲和力。EV 输注减轻了 MRI 观察到的 ICH 引起的病理变化，并减少了对同侧皮质神经元的损伤。RNA-Seq 分析表明，EV 处理调节了 ICH 小鼠中涉及神经元系统和金属离子转运的关键途径。这些数据得到了 Hemin 处理的神经元和 EV 治疗后的 ICH 小鼠中神经元铁死亡减弱的支持。此外，miRNA 微阵列分析描绘了 EV-miRNAs 靶向与铁死亡相关的基因，miR-214-3p 被鉴定为 ICH 细胞模型中神经元铁死亡的调节剂。
MSC-EVs 通过调节铁死亡对 ICH 诱导的神经元损伤具有神经保护作用，突出了它们在治疗脑疾病中铁死亡中的治疗潜力。
