Mesenchymal stem cells therapy protects fetuses from resorption and induces Th2 type cytokines profile in abortion prone mouse model

Abstract

The imbalance of Th1/Th2 cytokines is well known in recurrent spontaneous abortion (RSA) mouse model. Mesenchymal stem cells (MSCs) possess potent immunoregulatory properties that could modulate the Th1 cytokine responses in benefit of Th2 types. In this study, we aimed to analyze the local and systemic balance of Th1/Th2 cytokines following MSCs therapy.Syngeneic adipose derived MSCs were administered to abortion prone mice during the implantation window. The abortion rate was determined and IL-4, IL-6, IL-12, IL-2, IFN-γ and GM-CSF gene expression was evaluated by Real-Time-PCR in decidual and placental tissues of pregnant mice at day 13.5 of pregnancy. Splenocytes of pregnant mice were co-cultured with mitomycin C treated paternal splenocytes and IL-2, IL-4, IL-10 and IFN-γ cytokines were measured in co-cultures supernatants by ELISA method. Proliferation response of female splenocytes to paternal antigens was also evaluated using the CFSE method.Our results showed a significant reduction in abortion rate following MSCs administration in abortion prone mice. We also observed a significant down-regulation of IL-2 and IFN-γ as well as up-regulation of IL-4 and IL-10 production from pregnant mouse splenocytes following MSCs therapy along with a significant reduction of splenocytes proliferation against paternal antigens. Our findings revealed that MSCs therapy increased the IL-4, IL-6, IL-10 and GM-CSF and at the same time decreased the IL-12, IL-2 and IFN-γ gene expression at feto-maternal interface.Here, we showed that MSCs therapy could modulate the systemic as well as local Th1/Th2 cytokines production along with protection of fetus from resorption in abortion prone mice. The fine balance of Th1/Th2 cytokine response could be considered as one of the possible mechanisms for fetal protection following MSCs therapy.