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马属蹄部祖细胞表现出增加的线粒体代谢和对高度促炎微环境的适应潜力。

Equine Hoof Progenitor Cells Display Increased Mitochondrial Metabolism and Adaptive Potential to a Highly Pro-Inflammatory Microenvironment.

机构信息

Department of Experimental Biology, Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland.

International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mała, Poland.

出版信息

Int J Mol Sci. 2023 Jul 14;24(14):11446. doi: 10.3390/ijms241411446.

Abstract

Medicinal signaling cells (MSC) exhibit distinct molecular signatures and biological abilities, depending on the type of tissue they originate from. Recently, we isolated and described a new population of stem cells residing in the coronary corium, equine hoof progenitor cells (HPCs), which could be a new promising cell pool for the treatment of laminitis. Therefore, this study aimed to compare native populations of HPCs to well-established adipose-derived stem cells (ASCs) in standard culture conditions and in a pro-inflammatory milieu to mimic a laminitis condition. ASCs and HPCs were either cultured in standard conditions or subjected to priming with a cytokines cocktail mixture. The cells were harvested and analyzed for expression of key markers for phenotype, mitochondrial metabolism, oxidative stress, apoptosis, and immunomodulation using RT-qPCR. The morphology and migration were assessed based on fluorescent staining. Microcapillary cytometry analyses were performed to assess the distribution in the cell cycle, mitochondrial membrane potential, and oxidative stress. Native HPCs exhibited a similar morphology to ASCs, but a different phenotype. The HPCs possessed lower migration capacity and distinct distribution across cell cycle phases. Native HPCs were characterized by different mitochondrial dynamics and oxidative stress levels. Under standard culture conditions, HPCs displayed different expression patterns of apoptotic and immunomodulatory markers than ASCs, as well as distinct miRNA expression. Interestingly, after priming with the cytokines cocktail mixture, HPCs exhibited different mitochondrial dynamics than ASCs; however, the apoptosis and immunomodulatory marker expression was similar in both populations. Native ASCs and HPCs exhibited different baseline expressions of markers involved in mitochondrial dynamics, the oxidative stress response, apoptosis and inflammation. When exposed to a pro-inflammatory microenvironment, ASCs and HPCs differed in the expression of mitochondrial condition markers and chosen miRNAs.

摘要

药用信号细胞(MSC)根据其来源组织的类型表现出不同的分子特征和生物学能力。最近,我们分离并描述了一种存在于冠状真皮中的新型干细胞群,即马蹄祖细胞(HPC),这可能是治疗蹄叶炎的一种有前途的新细胞来源。因此,本研究旨在比较 HPC 的天然群体与标准培养条件下和模拟蹄叶炎条件下的成熟脂肪来源干细胞(ASC)。将 ASC 和 HPC 分别在标准条件下培养或用细胞因子鸡尾酒混合物进行预培养。收获细胞,使用 RT-qPCR 分析关键标记物以评估表型、线粒体代谢、氧化应激、细胞凋亡和免疫调节的表达。根据荧光染色评估形态和迁移。进行微毛细管细胞术分析以评估细胞周期、线粒体膜电位和氧化应激的分布。天然 HPC 的形态与 ASC 相似,但表型不同。HPC 的迁移能力较低,且细胞周期各阶段的分布也不同。天然 HPC 的线粒体动力学和氧化应激水平不同。在标准培养条件下,HPC 的凋亡和免疫调节标记物的表达模式与 ASC 不同,miRNA 表达也不同。有趣的是,在用细胞因子鸡尾酒混合物预培养后,HPC 的线粒体动力学与 ASC 不同;然而,两种细胞群的凋亡和免疫调节标记物表达相似。天然 ASC 和 HPC 表现出不同的线粒体动力学、氧化应激反应、细胞凋亡和炎症相关标志物的基线表达。当暴露于促炎微环境中时,ASC 和 HPC 在与线粒体状态相关的标记物和所选 miRNA 的表达上存在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4676/10379971/b62364f7686c/ijms-24-11446-g001.jpg

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