Mesenchymal stem cells induce expansion of regulatory T cells in abortion-prone mice

in Reproduction
Authors:
Amir Salek Farrokhi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

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Amir-Hassan Zarnani Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

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Fatemeh Rezaei kahmini Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

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Seyed Mohammad Moazzeni Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

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Correspondence should be addressed to S M Moazzeni; Email: Moazzeni@modares.ac.ir
DOI:
https://doi.org/10.1530/REP-20-0320
Volume/Issue:
Volume 161: Issue 4
Page Range:
477–487
Article Type:
Research Article
Online Publication Date:
Apr 2021
Copyright:
© 2021 Society for Reproduction and Fertility 2021
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Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate the immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph nodes, Ho1, Foxp3, Pd1 and Ctla4 genes expression at the feto–maternal interface were then measured on day 13.5 of pregnancy using flow cytometry and quantitative RT-PCR, respectively. The abortion rate in MSCs-treated mice reduced significantly and normalized to the level observed in normal pregnant animals. We demonstrated a significant induction of Tregs in inguinal lymph nodes but not in the spleen following MSCs administration. Administration of MSCs remarkably upregulated the expression of Ho1, Foxp3, Pd1 and Ctla4 genes in both placenta and decidua. Here, we show that MSCs therapy could protect the fetus in the abortion-prone mice through Tregs expansion and upregulation of Treg-related genes. These events could establish an immune-privileged microenvironment, which participates in the regulation of detrimental maternal immune responses against the semi-allogeneic fetus.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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