Sadighi-Moghaddam Bizhan, Salek Farrokhi Amir, Namdar Ahmadabad Hassan, Barati Mehdi, Moazzeni Seyed Mohammad
1 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
2 Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Reprod Sci. 2018 Aug;25(8):1261-1269. doi: 10.1177/1933719117737848. Epub 2017 Nov 29.
Immunological disorders are among the main causes of recurrent spontaneous abortions (RSAs). Mesenchymal stem cells (MSCs) have been shown to modulate various aspects of immune responses. It seems that MSCs may improve the immunological conditions in immune-mediated RSA. The aim of this study is the reduction of resorption in RSA mouse model through MSCs therapy. The adipose-derived MSCs were administered intraperitoneal to pregnant CBA/J mice on day 4.5 of gestation in abortion-prone matting. On day 13.5 of pregnancy, abortion rates were calculated and transforming growth factor-β (TGF-β), interleukin 10 (IL-10), interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) gene expression in deciduas were evaluated by real-time polymerase chain reaction (PCR). The level of TGF-β in serum was also determined by enzyme linked immunosorbent assay (ELISA) method. The obtained results showed that MSCs therapy could reduce the abortion rate significantly in test group compared to controls. MSCs therapy also caused a significant upregulation of TGF-β and IL-10 and downregulation of IFN-γ and TNF-α genes expression in deciduas. However, the levels of TGF-β didn't change in mice sera. Due to the significant decrease in abortion rate, we concluded that MSCs therapy could modulate the immune responses in fetomaternal interface and protect fetus from undesirable immune responses. So, these cells might be considered as a new therapeutic for spontaneous pregnancy loss. The local upregulation of TGF-β and IL-10 and downregulation of IFN-γ and TNF-α gene expression in decidua could be considered as one possible mechanism of immune regulation, which could protect the fetus.
免疫紊乱是复发性自然流产(RSA)的主要原因之一。间充质干细胞(MSCs)已被证明可调节免疫反应的各个方面。似乎MSCs可能改善免疫介导的RSA中的免疫状况。本研究的目的是通过MSCs治疗降低RSA小鼠模型中的流产率。在易流产交配的妊娠第4.5天,将脂肪来源的MSCs腹腔注射给怀孕的CBA/J小鼠。在妊娠第13.5天,计算流产率,并通过实时聚合酶链反应(PCR)评估蜕膜中转化生长因子-β(TGF-β)、白细胞介素10(IL-10)、干扰素γ(IFN-γ)和肿瘤坏死因子α(TNF-α)基因的表达。血清中TGF-β的水平也通过酶联免疫吸附测定(ELISA)方法测定。获得的结果表明,与对照组相比,MSCs治疗可显著降低试验组的流产率。MSCs治疗还导致蜕膜中TGF-β和IL-10的显著上调以及IFN-γ和TNF-α基因表达的下调。然而,小鼠血清中TGF-β的水平没有变化。由于流产率显著降低,我们得出结论,MSCs治疗可调节母胎界面的免疫反应,并保护胎儿免受不良免疫反应的影响。因此,这些细胞可能被视为治疗自然流产的一种新疗法。蜕膜中TGF-β和IL-10的局部上调以及IFN-γ和TNF-α基因表达的下调可被视为一种可能的免疫调节机制,其可保护胎儿。