Mesenchymal stem cells‐derived exosomes improve pregnancy outcome through inducing maternal tolerance to the allogeneic fetus in abortion‐prone mating mouse

• Published in: The Kaohsiung journal of medical sciences 2020-05, Vol.36 (5), p.363-370
• Main Authors: Xiang, Yan‐Jie, Hou, Yan‐Yan, Yan, Hong‐Li, Liu, Hui, Ge, Yan‐Xin, Chen, Na, Xiang, Jian‐Feng, Hao, Cui‐Fang
• Format: Article
• Language: English
• Subjects: Abortion; Analysis; Antibodies; Bone marrow; Cell culture; Cytokines; exosome; Females; Flow cytometry; Interferon; mesenchymal stem cell; MicroRNAs; Miscarriage; Penicillin; Pregnancy; Pregnant women; recurrent pregnancy loss; Statistical analysis; Stem cells; T cells; Transmission electron microscopy; Vagina
• ISSN: 1607-551X; 2410-8650
• DOI: 10.1002/kjm2.12178

Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. In the present study, bone marrow mesenchymal stem cells were isolated from CBA/J female mice and exosomes were isolated from cell culture medium by ultracentrifugation. CBA/J female mice were paired with male DBA/2 to generate abortion prone mouse model, and CBA/J females paired with male BALB/c mice were used as control. Exosomes were injected through uterine horns into 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 the level of transforming growth factor‐β (TGF‐β), interleukin 10 (IL‐10), interferon g (IFN‐γ), and tumor necrosis factor a (TNF‐α) in CD4+ T cells and macrophages in deciduas were evaluated by flow cytometry. Exosomes injection improved the pregnancy outcomes in abortion prone mice. The IL‐4 and IL‐10 levels on CD4+ T cells were upregulated in the maternal–fetal interface; meanwhile, the TNF‐α and IFN‐γ levels on CD4+ T cells were reduced. The IL‐10 level was increased and IL‐12 was reduced on the monocytes that separated from deciduas. miR‐101 level was increased in the CD4+ T cells in the deciduas. In conclusion, the treatment of ESCs‐derived exosomes modulates T cells' function and macrophages activities in the maternal–fetal interface that resulted in a decreased embryo resorption rate, and provides a therapeutic potential to treat RPL.