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

IF 1.1 4区 医学 Q4 TOXICOLOGY Molecular & Cellular Toxicology Pub Date : 2023-12-16 DOI:10.1007/s13273-023-00415-5
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引用次数: 0

摘要

摘要 背景 多发性骨髓瘤(MM)细胞和骨髓间充质基质细胞(MSCs)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,目前仍不清楚 MM 细胞和间充质干细胞是如何相互影响以诱发这些现象的。 本研究主要观察 MM 细胞诱导间充质干细胞发生的变化。通过评估细胞增殖、凋亡、细胞周期和形态,观察间充质干细胞暴露于 MM 细胞后的变化。此外,还通过分化潜能、间充质干细胞标记物的表达以及衰老的证明,证实了间充质干细胞的独特能力。为了阐明这些变化的机制,还进行了基因分析。 结果 MM 细胞与间充质干细胞共培养不会改变间充质干细胞的形态或增殖,但会增加细胞凋亡。随着凋亡的增加,受损的脱氧核糖核酸(DNA)被修复,导致细胞周期被激活,S期增加,但细胞增殖和形态没有发生显著变化。与 MM 细胞共培养后,骨生成和脂肪生成普遍减少,衰老增加。在间充质干细胞标记基因的表达方面观察到了显著差异。基因谱分析显示,成骨分化后基因表达发生了变化。 结论 基于这些结果,暴露于 MM 细胞的间充质干细胞表现出细胞周期 S 期的增加,导致凋亡细胞的恢复。骨生成和脂肪生成减少,而衰老增加,这表明这些变化归因于间充质干细胞的整体特征和遗传机制。
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Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells

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.

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来源期刊
CiteScore
2.50
自引率
17.60%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Molecular & Cellular Toxicology publishes original research and reviews in all areas of the complex interaction between the cell´s genome (the sum of all genes within the chromosome), chemicals in the environment, and disease. Acceptable manuscripts are the ones that deal with some topics of environmental contaminants, including those that lie in the domains of analytical chemistry, biochemistry, pharmacology and toxicology with the aspects of molecular and cellular levels. Emphasis will be placed on toxic effects observed at relevant genomics and proteomics, which have direct impact on drug development, environment health, food safety, preventive medicine, and forensic medicine. The journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.
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