Proteomic insights uncover enhanced neurotherapeutic potential in conditioned mesenchymal stem cell-derived extracellular vesicles

Extracellular vesicle Pub Date : 2024-04-20 DOI:10.1016/j.vesic.2024.100037

Junxiu Xi , Tian Wang , Panpan Xian , Xiaoyan Liu , Minghao Du , Hao Yang , Perumal Palanisamy Chella , Wei Lin , Qianfa Long

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Abstract

Extracellular vesicles (EVs) show more potential as therapeutic agents for treating neurological disorders than their parent cells like MSCs. Notably, the therapeutic efficacy of MSCs can be boosted by inflammation factors and oxidative stressors. Here, we investigated the impact of activated microglial cell supernatant (Con1) and hydrogen peroxide (Con2) on MSCs and collected their derived EVs, followed by using high-resolution mass spectrometry to analyze MSC-EV proteomic and phosphoproteomic profiles, and verified the indicated functional protein and phosphorylated kinase as well. Our findings showed that both Con1 and Con2 EVs exhibited characteristic features of extracellular vesicles and possessed greater anti-inflammatory and antioxidant activity compared to unconditioned MSC-EVs. Omics analysis revealed alterations in protein expression and phosphorylation associated with inflammation and oxidation biological processes and signaling pathways, as well as signified the post-translational modification of proteins in Con1/2 EVs. Importantly, we identified that the anti-inflammatory role of MSC-EVs was linked to the serine/threonine kinase phosphorylation, and inhibition of insulin-like growth factor 1 receptor (IGF1R) reduced the antioxidant activity of MSC-EVs. This report documented the changed protein expression and phosphorylated patterns of Con1/2 EVs, and provided insights into the functionalization mode of MSC-EVs, suggesting the enhanced neurotherapeutic potential of conditioned EVs in the treatment of neurological diseases.

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蛋白质组学研究发现条件间充质干细胞衍生的细胞外囊泡具有更强的神经治疗潜力

与间充质干细胞等母细胞相比，细胞外囊泡（EVs）在治疗神经系统疾病方面显示出更大的治疗潜力。值得注意的是，间充质干细胞的疗效会受到炎症因子和氧化应激因子的影响。在此，我们研究了活化的小胶质细胞上清液（Con1）和过氧化氢（Con2）对间充质干细胞的影响，并收集了其衍生的EV，随后使用高分辨率质谱分析了间充质干细胞-EV的蛋白质组和磷酸化蛋白质组谱分析，并验证了所指示的功能蛋白和磷酸化激酶。我们的研究结果表明，Con1 和 Con2 EVs 都表现出细胞外囊泡的特征，与未调理的间充质干细胞-EVs 相比，它们具有更强的抗炎和抗氧化活性。Omics分析揭示了与炎症和氧化生物过程及信号通路相关的蛋白质表达和磷酸化的改变，并显示了Con1/2 EVs中蛋白质的翻译后修饰。重要的是，我们发现间充质干细胞-EVs的抗炎作用与丝氨酸/苏氨酸激酶磷酸化有关，而抑制胰岛素样生长因子1受体（IGF1R）会降低间充质干细胞-EVs的抗氧化活性。该报告记录了Con1/2 EVs蛋白表达和磷酸化模式的变化，并深入揭示了间充质干细胞-EVs的功能化模式，表明条件EVs在治疗神经系统疾病方面具有更高的神经治疗潜力。

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

Extracellular vesicle Biochemistry, Genetics and Molecular Biology (General)

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审稿时长

43 days