Unidad de Inmunología, IBIMER, CIBM, Universidad de Granada, Granada, Spain.
Departamento de Bioquímica y Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Sci Rep. 2020 Dec 7;10(1):21389. doi: 10.1038/s41598-020-78423-x.
Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.
经血源基质细胞(MenSCs)由于其免疫调节特性,成为细胞治疗的有力候选者。然而,它们对固有免疫群体的直接影响仍不清楚。由于巨噬细胞在炎症的发生和发展中起着关键作用,因此了解 MenSCs 对这些细胞功能特性的影响对于在治疗炎症性疾病时细化其临床效果是必要的。在这项研究中,我们评估了 MenSCs 在两种急性炎症小鼠模型(巯基醋酸盐(TGC)诱导的腹膜炎模型和单细菌败血症模型)中对巨噬细胞和其他固有免疫细胞募集的影响。我们发现,在 TGC 模型中,MenSCs 注射减少了募集到腹膜中的巨噬细胞的百分比,并促进了腹膜免疫细胞聚集的产生。在败血症模型中,MenSCs 通过减少巨噬细胞和中性粒细胞向感染部位的募集并诱导细菌清除缺陷,加重了感染。额外的体外研究证实,与 MenSCs 共培养会损害巨噬细胞的杀菌特性,影响细菌杀伤和活性氧中间体的产生。我们的研究结果表明,MenSCs 调节巨噬细胞群体,在考虑未来的临床应用时必须考虑到这种调节。