Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye Shosse, 76a, 123007 Moscow, Russia.
Cells. 2024 Aug 13;13(16):1345. doi: 10.3390/cells13161345.
Currently, there is a growing focus on aging and age-related diseases. The processes of aging are based on cell senescence, which results in changes in intercellular communications and pathological alterations in tissues. In the present study, we investigate the influence of senescent mesenchymal stem cells (MSCs) on endothelial cells (ECs). In order to induce senescence in MSCs, we employed a method of stress-induced senescence utilizing mitomycin C (MmC). Subsequent experiments involved the interaction of ECs with MSCs in a coculture or the treatment of ECs with the secretome of senescent MSCs. After 48 h, we assessed the EC state. Our findings revealed that direct interaction led to a decrease in EC proliferation and migratory activity of the coculture. Furthermore, there was an increase in the activity of the lysosomal compartment, as well as an upregulation of the genes , , , , and . Treatment of ECs with the "senescent" secretome resulted in less pronounced effects, although a decrease in proliferation and an increase in ICAM-1 expression were observed. The maintenance of high levels of typical "senescent" cytokines and growth factors after 48 h suggests that the addition of the "senescent" secretome may have a prolonged effect on the cells. It is noteworthy that in samples treated with the "senescent" secretome, the level of PDGF-AA was higher, which may explain some of the pro-regenerative effects of senescent cells. Therefore, the detected changes may underlie both the negative and positive effects of senescence. The findings provide insight into the effects of cell senescence in vitro, where many of the organism's regulatory mechanisms are absent.
目前，人们越来越关注衰老和与年龄相关的疾病。衰老过程基于细胞衰老，这导致细胞间通讯的变化和组织的病理改变。在本研究中，我们研究了衰老间充质干细胞（MSCs）对内皮细胞（ECs）的影响。为了诱导 MSCs 衰老，我们采用丝裂霉素 C（MmC）诱导的应激衰老方法。随后的实验涉及 ECs 与 MSC 的共培养或用衰老 MSC 的分泌组处理 ECs。48 小时后，我们评估了 EC 的状态。我们的研究结果表明，直接相互作用导致共培养物中 EC 的增殖和迁移活性降低。此外，溶酶体区室的活性增加，以及基因 、 、 、 和 的表达上调。用“衰老”分泌组处理 ECs 时，效果不太明显，但观察到增殖减少和 ICAM-1 表达增加。48 小时后，典型的“衰老”细胞因子和生长因子的维持水平较高，表明添加“衰老”分泌组可能对细胞有较长的影响。值得注意的是，在用“衰老”分泌组处理的样本中，PDGF-AA 的水平更高，这可能解释了衰老细胞的一些促再生作用。因此，检测到的变化可能是衰老的阴性和阳性影响的基础。这些发现深入了解了体外细胞衰老的影响，因为许多机体的调节机制都不存在。
