Impact of Pro-Inflammatory Cytokine Preconditioning on Metabolism and Extracellular Vesicles in Feline Mesenchymal Stromal Cells: A Preliminary Study.

IF 4 2区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

STEM CELLS Pub Date : 2025-04-01 DOI:10.1093/stmcls/sxaf014

Maria Soltero-Rivera, Boaz Arzi, Lynda Bourebaba, Krzysztof Marycz

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引用次数: 0

Abstract

Background: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have shown promise in treating inflammation. This study investigates whether preconditioning feline adipose-derived stem cells (FeASCs) with inflammatory cytokines, specifically IFN-γ and TNF-α, enhances the anti-inflammatory efficacy of MSC-derived EVs.

Objective: We hypothesize that cytokine-primed FeASCs will produce EVs with improved anti-inflammatory properties and that this preconditioning will affect mitochondrial dynamics to enhance EV therapy effectiveness.

Methods: FeASCs were exposed to TNF-α / IFN-γ combination to mimic a pro-inflammatory milieu favoring ASCs immunosuppressive phenotype. We analyzed morphological, metabolic, and immunomodulatory characteristics of native and cytokine-primed FeASCs. EVs were assessed for anti-inflammatory and mitochondrial-related markers. We also evaluated mitochondrial function and apoptosis markers in cytokine-primed cells.

Results: Cytokine priming led to significant morphological changes in FeASCs, including enhanced cell projections and increased apoptosis. EVs from cytokine-primed FeASCs exhibited a heightened immunomodulatory profile, with increased expression of both pro-inflammatory and anti-inflammatory mediators. Transcriptomic analysis of these EVs revealed the upregulation of genes associated with cell proliferation, survival, and apoptosis. Mitochondrial function was impaired in cytokine-primed cells, but mitochondrial morphology remained unchanged. EVs from these cells contained higher levels of mitochondrial-related transcripts, indicating a compensatory response.

Conclusion: Cytokine-primed FeASCs generate EVs with enhanced immunomodulatory potential, highlighting their therapeutic promise. However, further research is needed to validate their efficacy and safety and refine preconditioning strategies to optimize EV-based therapies for inflammatory conditions. These advancements could pave the way for broader applications in regenerative medicine.

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背景：从间充质干细胞（MSCs）中提取的细胞外囊泡（EVs）已显示出治疗炎症的前景。本研究探讨了用炎症细胞因子（特别是 IFN-γ 和 TNF-α）预处理猫脂肪来源干细胞（FeASCs）是否能增强间充质干细胞衍生的 EVs 的抗炎功效：我们假设细胞因子刺激的 FeASCs 将产生具有更好抗炎特性的 EVs，并且这种预处理将影响线粒体动力学，从而提高 EV 治疗的效果：方法：将 FeASCs 暴露于 TNF-α / IFN-γ 组合，以模拟有利于 ASCs 免疫抑制表型的促炎环境。我们分析了原生和细胞因子激发的 FeASCs 的形态、代谢和免疫调节特征。我们对EV进行了抗炎和线粒体相关标记物的评估。我们还评估了细胞因子激发细胞的线粒体功能和凋亡标志物：结果：细胞因子引物导致 FeASCs 发生了显著的形态学变化，包括细胞突起增强和细胞凋亡增加。细胞因子激发的 FeASCs 的 EVs 表现出更强的免疫调节特征，促炎和抗炎介质的表达都有所增加。对这些EVs的转录组分析表明，与细胞增殖、存活和凋亡相关的基因上调。细胞因子激发的细胞线粒体功能受损，但线粒体形态保持不变。这些细胞的EVs含有更高水平的线粒体相关转录本，表明存在补偿反应：结论：细胞因子刺激的 FeASCs 产生的 EVs 具有更强的免疫调节潜力，突显了其治疗前景。然而，还需要进一步的研究来验证其疗效和安全性，并完善预处理策略，以优化基于 EV 的炎症疗法。这些进展将为再生医学的更广泛应用铺平道路。

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

STEM CELLS 医学-生物工程与应用微生物

CiteScore

10.30

自引率

1.90%

发文量

104

审稿时长

3 months

期刊介绍： STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.