Abstract

Backgrounds

The direct and indirect interactions between multiple myeloma (MM) cells and bone marrow mesenchymal stromal cells (MSCs) play crucial roles in the formation of the bone marrow environment, disease progression, and drug resistance development. However, it remains unclear how MM cells and MSCs individually influence each other to induce these phenomena.

Objective

In this study, we focused on observing changes in MSCs induced by MM cells. Changes in MSCs due to exposure to MM cells were observed by assessing cell proliferation, apoptosis, cell cycle, and morphology. Furthermore, the unique abilities of MSCs were confirmed through differentiation potential and MSC marker expression, along with the demonstration of senescence. Gene profiling was performed to elucidate the mechanisms underlying these changes.

Results

Co-culturing MM cells with MSCs did not alter the morphology or proliferation of MSCs but increased apoptosis. As apoptosis increased, damaged deoxyribonucleic acid (DNA) was repaired, leading to the activation of the cell cycle with an increase in the S phase, resulting in no significant changes in cell proliferation and morphology. Osteogenesis and adipogenesis generally decreased by co-culturing with MM cells, and senescence increased. Significant differences were observed in the expression of MSC marker genes. Gene profiling revealed changes in gene expression following osteogenic differentiation.

Conclusion

Based on these results, MSCs exposed to MM cells exhibited an increase in the S phase of the cell cycle, leading to the recovery of cells undergoing apoptosis. Osteogenesis and adipogenesis decreased, whereas senescence increased, suggesting that these changes were attributed to the overall MSC characteristics and genetic mechanisms.

中文翻译：

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暴露于多发性骨髓瘤细胞的骨髓间充质干细胞的表型和功能改变

 抽象的

 背景

多发性骨髓瘤（MM）细胞与骨髓间充质基质细胞（MSC）之间的直接和间接相互作用在骨髓环境的形成、疾病进展和耐药性发展中发挥着至关重要的作用。然而，目前尚不清楚MM细胞和MSC如何单独影响彼此以诱导这些现象。

 客观的

在本研究中，我们重点观察MM细胞诱导的MSCs的变化。通过评估细胞增殖、凋亡、细胞周期和形态来观察由于暴露于MM细胞而引起的MSC的变化。此外，通过分化潜能和MSC标志物表达以及衰老的证明，证实了MSC的独特能力。进行基因分析是为了阐明这些变化背后的机制。

 结果

MM细胞与MSC共培养并没有改变MSC的形态或增殖，但增加了细胞凋亡。随着细胞凋亡的增加，受损的脱氧核糖核酸（DNA）被修复，导致细胞周期激活，S期增加，导致细胞增殖和形态没有明显变化。与MM细胞共培养时，骨生成和脂肪生成通常会减少，并且衰老会增加。 MSC 标记基因的表达观察到显着差异。基因分析揭示了成骨分化后基因表达的变化。

 结论

基于这些结果，暴露于MM细胞的MSC表现出细胞周期S期的增加，导致细胞凋亡的恢复。成骨和脂肪生成减少，而衰老增加，表明这些变化归因于整体 MSC 特征和遗传机制。