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干扰素-γ在小鼠骨髓间充质干细胞中诱导出类似衰老的特征。

IFN-γ induces senescence-like characteristics in mouse bone marrow mesenchymal stem cells.

作者信息

Yang Zhou Xin, Mao Gen Xiang, Zhang Jing, Wen Xiao Lin, Jia Bing Bing, Bao Yi Zhong, Lv Xiao Ling, Wang Ya Zhen, Wang Guo Fu

机构信息

Zhejiang Provincial Key Lab of Geriatrics, Zhejiang Hospital, Hangzhou, China.

出版信息

Adv Clin Exp Med. 2017 Mar-Apr;26(2):201-206. doi: 10.17219/acem/61431.

Abstract

BACKGROUND

Mesenchymal stem cells (MSC) are considered promising in tissue repair and regeneration medicine due to their proliferation and differentiation ability. Many properties of MSC are affected by cytokines, and IFN-γ has been shown to regulate MSC in many aspects. Senescence affects the proliferation, differentiation and cytokine secretion of MSC.

OBJECTIVES

To investigate the effects of IFN-γ on the senescence-associated properties of MSC.

MATERIAL AND METHODS

The MSC used in our study were isolated from the bone marrow (BM) of mice. Cell vitalities were measured by CCK8. The phenotypes and ROS of mBM-MSC were analyzed by flow cytometry. Cellular senescence was detected using SA-β-gal stains. IL-6 and CXCL1 secretions were measured by ELISA.

RESULTS

mBM-MSC can differentiated into osteocytes and adipocytes. They expressed CD29, CD106, and Sca-1, and did not express CD31, CD45 or FLK1. Our study showed that the cell vitalities of mBM-MSC were significantly reduced after IFN-γ treatment for 5 days, and the cell numbers were obviously lower after IFN-γ treatment for 5, 10 or 15 days. The IFN-γ group increased SA-β-gal-positive cells and reactive oxygen species (ROS) significantly after 15 days of IFN-γ treatment. Moreover, IL-6 and CXCL1 secretions were upregulated by IFN-γ.

CONCLUSIONS

Our study shows IFN-γ can induce senescence-like characteristics in mBM-MSC, suggesting a novel target for anti-aging therapy.

摘要

背景

间充质干细胞(MSC)因其增殖和分化能力,在组织修复和再生医学中被认为具有广阔前景。MSC的许多特性受细胞因子影响,且已表明干扰素-γ(IFN-γ)在多个方面调节MSC。衰老会影响MSC的增殖、分化和细胞因子分泌。

目的

研究IFN-γ对MSC衰老相关特性的影响。

材料与方法

本研究中使用的MSC从小鼠骨髓(BM)中分离。通过CCK8测定细胞活力。采用流式细胞术分析小鼠骨髓间充质干细胞(mBM-MSC)的表型和活性氧(ROS)。使用衰老相关β-半乳糖苷酶(SA-β-gal)染色检测细胞衰老。通过酶联免疫吸附测定(ELISA)检测白细胞介素-6(IL-6)和CXC趋化因子配体1(CXCL1)的分泌。

结果

mBM-MSC可分化为骨细胞和脂肪细胞。它们表达CD29、CD106和干细胞抗原-1(Sca-1),不表达CD31、CD45或胎儿肝脏激酶1(FLK1)。我们的研究表明,IFN-γ处理5天后,mBM-MSC的细胞活力显著降低,IFN-γ处理5、10或15天后细胞数量明显减少。IFN-γ处理15天后,IFN-γ组的SA-β-gal阳性细胞和活性氧(ROS)显著增加。此外,IFN-γ上调IL-6和CXCL1的分泌。

结论

我们的研究表明IFN-γ可诱导mBM-MSC出现衰老样特征,提示其可能成为抗衰老治疗的新靶点。

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