Mesenchymal Stem Cell-derived Extracellular Vesicles Mitigate Neuronal Damage from Intracerebral Hemorrhage by Modulating Ferroptosis

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2024 Aug 12

PMID 39135135

Authors

Yanping Yang

Lingfeng Gao

Junxiu Xi

Xiaoyan Liu

Hao Yang

Qiang Luo

Fei Xie

Jinyun Niu

Panpan Meng

Xiao Tian

Xiaoping Wu

Qianfa Long

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: MSC-EVs offer neuroprotective effects against ICH-induced neuronal damage by modulating ferroptosis highlighting their therapeutic potential for combating neuronal ferroptosis in brain disorders.

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