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丁香酚促进体外培养的小鼠骨髓间充质干细胞的增殖和迁移。

Eugenol enhances proliferation and migration of mouse bone marrow-derived mesenchymal stem cells in vitro.

机构信息

Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.

Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.

出版信息

Environ Toxicol Pharmacol. 2018 Jan;57:166-174. doi: 10.1016/j.etap.2017.12.012. Epub 2017 Dec 17.

Abstract

Mesenchymal stem cells (MSCs) have received considerable attention in regenerative medicine during the past decade. Eugenol is a natural and versatile vegetable molecule, which has a wide variety of therapeutic effects. Although different biological and pharmaceutical functions of Eugenol are well known, its effect on MSCs has not been studied yet. Therefore, this study was focused on investigating the effect of Eugenol on the proliferation and migration of bone marrow (BM)-derived MSCs in vitro. To do so, BM-MSCs were isolated from 4 to 8 weeks old NMRI mice. Cytotoxicity of Eugenol on MSCs was evaluated by MTT assay at 24, 48 and 72 h after treatment. In addition, its effect was assessed on the proliferation and migration of MSCs using wound healing assay in vitro and quantitative gene expression analysis for Oct4, Sox2, Cyclin-D1, Rex1, Tex10, Cxcr4, Vla4 and c-Met. Results showed that Eugenol reduced the number of MSCs in a dose- and time-dependent manner. The median inhibition concentration of Eugenol on MSCs was 400 μg/ml at 24 and 48 h and 200 μg/ml at 72 h after treatment. Moreover, about 90% viability of MSCs was detected at concentrations ≤12.5 μg/ml. The wound healing assay and gene expression analysis demonstrated that Eugenol promoted the migratory potential of MSCs through up-regulation of c-Met. Moreover, Eugenol has enhanced the proliferation of MSCs via over-expression of Sox2, Rex1 and Tex10. In conclusion, this study revealed that Eugenol enhances the proliferation and migration of MSCs, and thus this will be beneficial to the field of regenerative medicine.

摘要

间质干细胞(MSCs)在过去十年的再生医学中受到了广泛关注。丁香酚是一种天然且多功能的植物分子,具有广泛的治疗作用。尽管丁香酚的不同生物学和药物学功能已广为人知,但它对 MSCs 的影响尚未得到研究。因此,本研究集中于研究丁香酚对体外骨髓(BM)来源的 MSCs 增殖和迁移的影响。为此,从 4 至 8 周龄的 NMRI 小鼠中分离 BM-MSCs。通过 MTT 测定法在处理后 24、48 和 72 小时评估丁香酚对 MSCs 的细胞毒性。此外,还通过体外划痕愈合试验和 Oct4、Sox2、Cyclin-D1、Rex1、Tex10、Cxcr4、Vla4 和 c-Met 的定量基因表达分析评估其对 MSCs 增殖和迁移的影响。结果表明,丁香酚以剂量和时间依赖的方式减少 MSCs 的数量。丁香酚对 MSCs 的半数抑制浓度在 24 和 48 小时为 400μg/ml,在 72 小时为 200μg/ml。此外,在浓度≤12.5μg/ml 时检测到 MSCs 的存活率约为 90%。划痕愈合试验和基因表达分析表明,丁香酚通过上调 c-Met 促进 MSCs 的迁移潜力。此外,丁香酚通过 Sox2、Rex1 和 Tex10 的过表达促进了 MSCs 的增殖。总之,本研究表明丁香酚增强了 MSCs 的增殖和迁移,这将有益于再生医学领域。

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