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利用间充质干细胞外泌体改善慢性肉芽肿病患者中性粒细胞的功能。

Improving the function of neutrophils from chronic granulomatous disease patients using mesenchymal stem cells' exosomes.

机构信息

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Hum Immunol. 2020 Oct-Nov;81(10-11):614-624. doi: 10.1016/j.humimm.2020.05.009. Epub 2020 Sep 3.

DOI:10.1016/j.humimm.2020.05.009
PMID:32891471
Abstract

In chronic granulomatous disease (CGD) patients, reactive oxygen species (ROS) production by neutrophils is impaired. So, they are susceptible to infections. Studies showed that, mesenchymal stem cells (MSCs) have protective effects on the function of neutrophils and an approach that MSCs use to apply their effects, is secreting soluble factors and exosomes. So, we investigated the effects of MSC-exosomes and MSC-conditioned media (MSC-CM) on the function and apoptosis of neutrophils in CGD patients. In this study, neutrophils were isolated from healthy donors and CGD patients and then incubated with exosomes or CM that were prepared from MSCs. Then, neutrophil respiratory burst, apoptosis and phagocytosis capacity were evaluated by NBT assay, Annexin V-PI method and Giemsa staining. It was demonstrated that both MSC-exosomes and CM could improve the phagocytosis capacity and ROS production of neutrophils in CGD patients and healthy donors. In contrast to the healthy group, in CGD patients, exosomes significantly reduced the percentage of viable neutrophils. This report indicated that MSC exosomes and CM could increase the function of the neutrophils isolated from CGD patients. But decreasing the number of the living cells is one of the limitations of them. However, it is hoped that this intervention will be developed in future studies to minimize its limitations.

摘要

在慢性肉芽肿病 (CGD) 患者中,中性粒细胞产生的活性氧 (ROS) 受损。因此,他们容易感染。研究表明,间充质干细胞 (MSC) 对中性粒细胞的功能具有保护作用,MSC 发挥作用的一种方法是分泌可溶性因子和外泌体。因此,我们研究了 MSC 外泌体和 MSC 条件培养基 (MSC-CM) 对 CGD 患者中性粒细胞功能和凋亡的影响。在这项研究中,从健康供体和 CGD 患者中分离中性粒细胞,然后用从 MSC 中制备的外泌体或 CM 孵育。然后,通过 NBT 测定、Annexin V-PI 法和吉姆萨染色评估中性粒细胞呼吸爆发、凋亡和吞噬能力。结果表明,MSC 外泌体和 CM 均可改善 CGD 患者和健康供体中性粒细胞的吞噬能力和 ROS 产生。与健康组相比,在 CGD 患者中,外泌体显著降低了活中性粒细胞的百分比。本报告表明,MSC 外泌体和 CM 可增强 CGD 患者分离的中性粒细胞的功能。但减少活细胞的数量是它们的局限性之一。然而,希望在未来的研究中进一步开发这种干预措施,以最大限度地减少其局限性。

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