• Open Access

Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis

Authors

  • Q. L. Fu,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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    • These authors equally contributed to this study.

  • Y. Y. Chow,

    1. Cardiology Division, Department of Medicine and Research Centre of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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    • These authors equally contributed to this study.

  • S. J. Sun,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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    • These authors equally contributed to this study.

  • Q. X. Zeng,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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  • H. B. Li,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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  • J. B. Shi,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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  • Y. Q. Sun,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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  • W. Wen,

    1. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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  • H. F. Tse,

    1. Cardiology Division, Department of Medicine and Research Centre of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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  • Q. Lian,

    1. Cardiology Division, Department of Medicine and Research Centre of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
    2. Eye Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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  • G. Xu

    Corresponding author
    • Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
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Correspondence

Prof. Geng Xu, MD, Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China.

Tel.: +86 20 87333733

Fax: +86 20 87333733

E-mail: entxgfess@163.com or to Dr Qizhou Lian, Department of Medicine and Eye Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21, Sassoon Road, Pokfulam, Hong Kong. Tel.: +852-28199752 Fax: +852-28162095 E-mail: qzlian@hku.hk

Abstract

Background

Human induced pluripotent stem cells (iPSCs) possess remarkable self-renewal capacity and the potential to differentiate into novel cell types, such as mesenchymal stem cells (MSCs). iPSC-MSCs have been shown to enhance tissue regeneration and attenuate tissue ischaemia; however, their contribution to the immune regulation of Th2-skewed allergic rhinitis (AR) and asthma remains unclear.

Objective

This study compared the immunomodulatory effects of iPSC-MSCs and bone marrow-derived MSCs (BM-MSCs) on lymphocyte proliferation, T-cell phenotypes and cytokine production in peripheral blood mononuclear cells (PBMCs) in patients with AR, and investigated the possible molecular mechanisms underlying the immunomodulatory properties of iPSC-MSCs.

Methods

In co-cultures of PBMCs with iPSC-MSCs or BM-MSCs, lymphocyte proliferation was evaluated using 3H-thymidine (3H-TdR) uptake, carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE) assays; the regulatory T-cell (Treg) phenotype was determined by flow cytometry, and cytokine levels were measured using an enzyme-linked immunosorbent assay. The immunomodulatory properties of both MSCs were further evaluated using NS398 and transwell experiments.

Results

Similar to BM-MSCs, we determined that iPSC-MSCs significantly inhibit lymphocyte proliferation and promote Treg response in PBMCs (< 0.05). Accordingly, the cytokine milieu (IFN-γ, IL-4, IL-5, IL-10 and IL-13) in the supernatants of PBMCs changed significantly (< 0.05). The immunomodulatory properties of iPSC-MSCs and BM-MSCs were associated with prostaglandin E2 (PGE2) production and cell–cell contact.

Conclusions

These data demonstrate that iPSC-MSCs are capable of modulating T-cell phenotypes towards Th2 suppression through inducing Treg expansion, suggesting that iPSC-MSCs can be used as an alternative candidate to adult MSCs to treat allergic airway diseases.

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