Mesenchymal Stem Cell Therapy Prevents Abortion in CBA/J × DBA/2 Mating

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. KEYWORDS: immunomodulation; mesenchymal stem cells; pregnancy; recurrent spontaneous abortions