Controlled induction of immune tolerance by mesenchymal stem cells transferred by maternal microchimerism

Sayuri Iwai; Aiko Okada; Kei Sasano; Masayuki Endo; Sho Yamazaki; Xin Wang; Takashi Shimbo; Takuji Tomimatsu; Tadashi Kimura; Katsuto Tamai

doi:10.1016/j.bbrc.2020.12.032

Controlled induction of immune tolerance by mesenchymal stem cells transferred by maternal microchimerism

Biochem Biophys Res Commun. 2021 Feb 5:539:83-88. doi: 10.1016/j.bbrc.2020.12.032. Epub 2021 Jan 16.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
² Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Japan; Department of Children's and Women's Health, Division of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. Electronic address: mendoh@sahs.med.osaka-u.ac.jp.
³ Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan; StemRIM Inc, Ibaraki, Osaka, Japan.
⁴ Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Japan.
⁵ Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan. Electronic address: tamai@gts.med.osaka-u.ac.jp.

PMID: 33461067
DOI: 10.1016/j.bbrc.2020.12.032

Abstract

Feto-maternal immune tolerance is established during pregnancy; however, its mechanism and maintenance remain underexplored. Here, we investigated whether mesenchymal stem/stromal cells (MSCs) as non-inherited maternal antigens (NIMAs) transferred by maternal microchimerism could induce immune tolerance. We showed that MSCs had a potential equivalent to hematopoietic stem and progenitor cells (HSPCs) to induce immune tolerance and that MSCs were essential to induce tolerance to MSC-specific antigens. Furthermore, we demonstrated that MSCs as NIMAs transferred by maternal microchimerism could induce robust immune tolerance that can be further enhanced using a drug. Our data shed light on induction of immune tolerance and serve as a foundation to develop new therapies using maternally derived cells for autoimmune or genetic diseases.

Keywords: Immune tolerance; MSC-Specific antigen; Maternal microchimerism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chimera / immunology*
Female
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / immunology*
Immune Tolerance
Maternal-Fetal Exchange / immunology*
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / immunology*
Mice
Mice, Inbred C57BL
Models, Animal
Pregnancy