Activated Endothelium Stimulates the Activity of Multipotent Mesenchymal Stromal Cells under Physiological Hypoxia or Short-Term Hypoxic Stress in vitro

IF 0.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Evolutionary Biochemistry and Physiology Pub Date : 2024-04-26 DOI:10.1134/s0022093024020194

O. V. Zhidkova, E. R. Andreeva, L. B. Buravkova

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Abstract

Multipotent mesenchymal stromal cells (MSCs) are used for supplementary therapy of ischemic and inflammatory diseases. After systemic administration, transmigration of MSCs to target tissues is accompanied by their interaction with activated endothelial cells (ECs) at the site of injury. In this study, we investigated the effects of TNF-α-activated ECs on MSC functions under different levels of hypoxia. For this purpose, the short-term direct co-culture of MSCs and activated TNF-α endothelial cells was used. MSCs retained their stromal phenotype and multilineage differentiation potential after the interaction with activated ECs. At the same time, there were detected changes in the expression of molecules involved in MSC contacts with other cells and the extracellular matrix (ECM), as well as in regulating ECM degradation and cell migration. Furthermore, conditioned medium from activated endothelium stimulated targeted and untargeted migration of MSCs. The interaction of MSCs with activated ECs enhanced the paracrine activity of both cell types due to upregulated transcription and elevated levels of pleiotropic cytokines IL-6 and IL-8, and altered the protease–antiprotease balance. These data suggest that short-term interaction of MSCs with activated ECs may play an important role in tissue reparative and remodeling processes. Specifically, it may promote the migratory phenotype of MSCs. In contrast to physiological hypoxia (5% O₂), acute hypoxic stress (0.1% O₂, 24 h) attenuated the stimulatory effects of ECs on MSCs.

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在体外生理缺氧或短期缺氧应激条件下，活化的内皮可刺激多能间质基质细胞的活性

摘要多能间充质基质细胞（MSCs）被用于缺血性和炎症性疾病的辅助治疗。系统给药后，间充质干细胞向靶组织的迁移伴随着它们与损伤部位活化的内皮细胞（ECs）的相互作用。在本研究中，我们研究了在不同程度的缺氧条件下 TNF-α 激活的内皮细胞对间叶干细胞功能的影响。为此，我们采用了间充质干细胞和活化的 TNF-α 内皮细胞短期直接共培养的方法。结果表明，间充质干细胞与活化的血管内皮细胞相互作用后，保留了其基质表型和多线分化潜能。同时，还检测到参与间充质干细胞与其他细胞和细胞外基质（ECM）接触以及调节 ECM 降解和细胞迁移的分子的表达发生了变化。此外，活化内皮的条件培养基刺激了间充质干细胞的定向和非定向迁移。间充质干细胞与活化的内皮细胞的相互作用增强了两种细胞类型的旁分泌活性，这是因为转录上调、多效细胞因子IL-6和IL-8水平升高，并改变了蛋白酶-抗蛋白酶的平衡。这些数据表明，间充质干细胞与活化的ECs的短期相互作用可能在组织修复和重塑过程中发挥重要作用。与生理性缺氧（5% O2）相比，急性缺氧应激（0.1% O2，24 小时）减弱了ECs对间叶干细胞的刺激作用。

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来源期刊

Journal of Evolutionary Biochemistry and Physiology 生物-进化生物学

自引率

33.30%

发文量

110

审稿时长

6-12 weeks

期刊介绍： Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.