Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Hum Immunol. 2019 Dec;80(12):990-998. doi: 10.1016/j.humimm.2019.10.006. Epub 2019 Nov 6.
Severe congenital neutropenia (SCN) is described by the absolute neutrophil counts less than 500 cells/mm, bacterial infections, and an arrest of neutrophil differentiation. So, effective strategies for improving the function and lifespan of the existing neutrophils in these patients are necessary. Mesenchymal stem cells (MSCs) have supportive effects on neutrophils. Recently, it was determined that MSCs exert their effects, mostly by secreting soluble factors and exosomes. So, in this study, neutrophils were isolated from the bloodstream of healthy donors and SCN patients and cultured with medium, MSC-exosomes or MSC-conditioned media (MSC-CM). Then, the effects of the two treatments on neutrophil respiratory burst, apoptosis and phagocytosis percentage were assessed using nitro blue tetrazolium (NBT) assay, annexin V-propidium iodide (PI) and Giemsa staining, respectively. Both treatments could significantly augment respiratory burst of neutrophils from SCN patients and healthy donors. But, only CM could significantly enhance phagocytosis index. About the lifespan of neutrophils, only exosomes could significantly enhance it in both groups. Based on these results, both exosomes and CM derived from MSCs could be attractive candidates for rescuing SCN patients from serious infections.
严重先天性中性粒细胞减少症 (SCN) 的特征是中性粒细胞绝对计数<500 个/毫米，伴有细菌感染和中性粒细胞分化停滞。因此，对于这些患者，需要寻找有效策略来改善现有中性粒细胞的功能和寿命。间充质干细胞 (MSCs) 对中性粒细胞具有支持作用。最近，研究发现 MSCs 主要通过分泌可溶性因子和外泌体发挥作用。因此，在本研究中，我们从健康供体和 SCN 患者的血液中分离中性粒细胞，并在培养基、MSC 外泌体或 MSC 条件培养基 (MSC-CM) 中培养。然后，使用硝基蓝四唑 (NBT) 测定、膜联蛋白 V-碘化丙啶 (PI) 和吉姆萨染色分别评估两种处理对中性粒细胞呼吸爆发、凋亡和吞噬百分比的影响。两种处理均能显著增强 SCN 患者和健康供体中性粒细胞的呼吸爆发。但只有 CM 能显著提高吞噬指数。关于中性粒细胞的寿命，只有外泌体能显著延长两组中性粒细胞的寿命。基于这些结果，MSC 来源的外泌体和 CM 都可能是拯救 SCN 患者严重感染的有吸引力的候选物。
