Bone mesenchymal stem cells improve pregnancy outcome by inducing maternal tolerance to the allogeneic fetus in abortion-prone matings in mouse

Introduction: The successful pregnancy depends on maternal immune tolerance against the fetus. It has been reported that MSCs (mesenchymal stem cells) could play a regulatory role on immune cells such as CD4(+)T cells, macrophages and NK cells, but their effect on recurrent miscarriage is unknown. Study design: In a prospective study, the abortion-prone (CBA/J x DBA/2) H-2(d) x H-2(k) mice were utilized. Female CBA/J mice (8-10 weeks old) were injected with vehicle or MSCs via tail vein or uterine horns, and 14 days later, they were mated with DBA/2 males for the following experiments. Results: Comparing with the control group, the embryo resorption rate in MSCs-horn injection group was dramatically decreased. MSCs were mainly located at the maternal-fetal interface, indicating that the reduction of resorption rate was due to MSCs' local effect. No matter which treatment was given, there was no significant difference in the levels of IL-4, IL-10, TNF-alpha and IFN-gamma in CD4(+)T cells and IL-10 and IL-12 in macrophages in spleens among each group. However, in contrast to other groups, the levels of IL-4 and IL-10 in CD4(+)T cells localized at the maternal-fetal interface in MSCs-horn injection group were dramatically increased, and INF-alpha and IFN-gamma levels were notably decreased. While IL-10 expressed in macrophages was obviously higher than other groups and IL-12 in macrophages was significantly lower than other groups. Conclusions: The findings indicate that MSCs injection through uterine horns could decrease embryo resorption rate. (C) 2016 Published by Elsevier Ltd.