Mesenchymal stem cells (MSCs) are regarded as unique cells which play an imperative role in the field of regenerative medicine. They are characterized by the self-renewal capacity, multi-lineage differentiation abilities and immunomodulation properties which render them perfectly ideal cell type for treating a wide range of chronic diseases. Despite these enchanted features, there are many hurdles that need to be circumvented to ensure their long-term survival and viability after transplantation. Recently, hypoxia has been indicated as one of the most baffling stress conditions that can affect the survival rate of MSCs either positively or negatively depending on the level of hypoxia. MSCs can survive well under moderate hypoxia, but die shortly if they were exposed to severe hypoxia without clearly convincing explanation for this enigma. The current study reveals a novel mechanism of 26S proteasome in controlling the ability of BM-MSCs to withstand hypoxic stress by maintaining proper mitochondrial function. The results indicated that 26S proteasome remains functioning once BM- MSCs are exposed to moderate hypoxia (2.5%O2) and preserves their survival and proliferation mediated by intact mitochondrial performance, whereas 26S proteasome becomes inactive when BM-MSCs faces severe hypoxia that lead to poor mitochondrial function and less chance to survive longer. The outcomes of this study demonstrated the importance of 26S proteasome machinery in enhancing the resistance of BM-MSCs to hypoxic stress condition which may help in better planning future studies that target this system. Schematic representation summarizing the findings of the current study. 26S proteasome function preservation in normoxia and moderate hypoxia leads to maintain appropriate proliferation and mitochondrial activity in human BM-MSCs and promote their survival. On the opposite side, severe hypoxia disrupts the 26S proteasome function leading to significant reduction in the proliferation, survival and mitochondrial dynamics in human BM-MSCs causing their death.

中文翻译：

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26S 蛋白酶体和线粒体之间的串扰影响人类间充质干细胞在缺氧应激下的生存能力。


间充质干细胞（MSC）被认为是在再生医学领域发挥着重要作用的独特细胞。它们的特点是自我更新能力、多谱系分化能力和免疫调节特性，这使得它们成为治疗多种慢性疾病的理想细胞类型。尽管有这些迷人的功能，但仍需要克服许多障碍，以确保它们在移植后长期存活和活力。最近，缺氧已被认为是最令人困惑的应激条件之一，它可以根据缺氧的程度对 MSC 的存活率产生积极或消极的影响。间充质干细胞在中度缺氧下可以很好地存活，但如果它们暴露在严重缺氧下，并且对这个谜团没有明确令人信服的解释，它们很快就会死亡。目前的研究揭示了26S蛋白酶体通过维持适当的线粒体功能来控制BM-MSC抵抗缺氧应激的能力的新机制。结果表明，一旦 BM-MSC 暴露于中度缺氧 (2.5%O2)，26S 蛋白酶体仍保持功能，并保持其由完整线粒体性能介导的存活和增殖，而当 BM-MSC 面临严重缺氧时，26S 蛋白酶体就会变得不活跃，导致细胞功能不良。线粒体功能受损，存活时间更长的机会更少。这项研究的结果证明了 26S 蛋白酶体机制在增强 BM-MSC 对缺氧应激条件的抵抗力方面的重要性，这可能有助于更好地规划针对该系统的未来研究。示意图总结了当前研究的结果。 常氧和中度缺氧下 26S 蛋白酶体功能的保存可维持人 BM-MSC 的适当增殖和线粒体活性并促进其存活。另一方面，严重缺氧会破坏 26S 蛋白酶体功能，导致人类 BM-MSC 的增殖、存活和线粒体动力学显着降低，从而导致其死亡。