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Immunosuppressive properties of Wharton’s jelly-derived mesenchymal stromal cells in vitro

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Abstract

Recent studies have reported that mesenchymal stromal cells (MSCs) migrate to areas of inflammation and suppress adverse immune reactions. Bone marrow (BM)-derived MSCs have been successfully used in patients with acute graft versus host disease (GVHD), but the harvesting of BM carries certain risks for the donor. To circumvent these, we obtained MSCs from Wharton’s jelly (WJ) derived from umbilical cord and investigated their potential for immunosuppression. In a mixed lymphocyte reaction (MLR), responder T cell proliferation triggered by allogeneic dendritic cells was inhibited efficiently by WJ-MSCs derived from the same donor of responder cells or those from a third party donor. These inhibitory effects were reversed in a dose-dependent manner in the presence of 1-methyl-DL-tryptophan, an inhibitor of the soluble factor indoleamine 2, 3-dioxygenase (IDO). Immunosuppression by WJ-MSCs was also attenuated by blocking cell–cell contact between WJ-MSCs and responder T cells using a Transwell chamber. Moreover, IDO gene expression was induced in both WJ- and BM-MSCs by inflammatory cytokine IFN-γ, but HLA-DR was expressed in BM-MSCs and not in WJ-MSCs upon stimulation by a relatively low concentration of IFN-γ. These results indicate that WJ-MSCs exert their immunosuppressive effects by cell–cell contact with activated T cells and in part through IDO, and suggest the need for cells rather than soluble factors secreted from MSCs to achieve immunosuppressive therapy in severe cases of GVHD.

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Abbreviations

1-MT:

1-Methyl-dl-tryptophan

BM:

Bone marrow

CB:

Cord blood

CFSE:

Carboxyfluorescein diacetate, succinimidyl ester

DC:

Dendritic cell

GVHD:

Graft versus host disease

IDO:

Indoleamine 2, 3-dioxygenase

MNC:

Mononuclear cell

MSC:

Mesenchymal stromal cell

UC:

Umbilical cord

WJ:

Wharton’s jelly

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Acknowledgments

This study was supported by the Ministry of Health, Labor and Welfare and the Ministry of Education, Culture, Sports, Science and Technology of Japan (H26-Regeneration-010). The authors thank Ms. Y. Yuzawa and Y. Enomoto for their technical support, as well as the staff at the NTT Medical Center Hospital (Tokyo) for assistance with the collection of UC tissue and CB.

Author information

Author notes

  1. Haiping He

    Present address: Department of Hematology, First People Hospital of Yunnan Province, Kunming, China

Authors and Affiliations

  1. Division of Molecular Therapy, Center for Advanced Medical Research, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Haiping He & Arinobu Tojo

  2. Department of Cell Processing and Transfusion, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Haiping He, Tokiko Nagamura-Inoue, Atsuko Takahashi, Yuka Mori, Yuki Yamamoto, Takahisa Shimazu & Arinobu Tojo

  3. Department of Obstetrics, NTT Medical Center Tokyo Hospital, 5-9-22, Higashigotanda, Shinagawa, Tokyo, 141-0022, Japan

    Hajime Tsunoda

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  1. Haiping He
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Correspondence to Tokiko Nagamura-Inoue.

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The authors have no financial interest/relationships with financial interest relating to the topic of this article have been declared.

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12185_2015_1844_MOESM1_ESM.tif

Supplementary material 1 (TIFF 80 kb) Supplementary Fig. 1. Cell number of responder cells (R) in MLR with or without Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs). The responder cells were counted by trypanblue staining in indicated conditions. Left column indicates R + stimulator cells (allogeneic DCs); middle column; R + stimulator cells +WJ-MSCs; and right column; R only. 1; Peripheral blood derived MNCs as responder cells, 2 to 4; Cord blood derived MNCs as responder cells

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He, H., Nagamura-Inoue, T., Takahashi, A. et al. Immunosuppressive properties of Wharton’s jelly-derived mesenchymal stromal cells in vitro. Int J Hematol 102, 368–378 (2015). https://doi.org/10.1007/s12185-015-1844-7

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  • DOI: https://doi.org/10.1007/s12185-015-1844-7

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