Date Published: October 01, 2012
Publisher: Blackwell Publishing Ltd
Author(s): Q L Fu, Y Y Chow, S J Sun, Q X Zeng, H B Li, J B Shi, Y Q Sun, W Wen, H F Tse, Q Lian, G Xu, Hans-Uwe Simon.
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.
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.
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.
Similar to BM-MSCs, we determined that iPSC-MSCs significantly inhibit lymphocyte proliferation and promote Treg response in PBMCs (P < 0.05). Accordingly, the cytokine milieu (IFN-γ, IL-4, IL-5, IL-10 and IL-13) in the supernatants of PBMCs changed significantly (P < 0.05). The immunomodulatory properties of iPSC-MSCs and BM-MSCs were associated with prostaglandin E2 (PGE2) production and cell–cell contact. 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.
This study includes 22 patients with persistent allergic rhinitis (AR) and 34 healthy donors (the details are listed in Table S1). The diagnosis of persistent AR was in accordance with the criteria of the initiative from Allergic Rhinitis and its Impact on Asthma (ARIA) 1. All patients were positive for Dermatophagoides pteronyssinus (Der p1) (Pharmacia CAP system, Pharmacia Diagnostics, Uppsala, Sweden). The patients had not received antihistamines or intranasal steroid treatments for 1 week, or oral steroids for 3 months, prior to this study. The Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University approved this study, and informed consent was obtained from all participants.
In this study, we took advantage of a short-term, in vitro culture system to provide preliminary evidence that similar to BM-MSCs, human iPSC-MSCs exert immunomodulatory effects on T-cell phenotypes in PBMCs from patients with AR. To our knowledge, this is the first study to compare the potential of iPSC-MSCs and BM-MSCs in the modulation of the allergic response, shedding light on the clinical use of iPSC-MSCs for the prevention of allergic airway diseases.