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The therapeutic efficacy of human adipose tissue‐derived mesenchymal stem cells on experimental autoimmune hearing loss in mice
Author(s) -
Zhou Yixuan,
Yuan Jingdong,
Zhou Bin,
Lee Austin J.,
Lee Albert J.,
Ghawji Jr Maher,
Yoo Tai June
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03421.x
Subject(s) - foxp3 , immunology , il 2 receptor , immune system , mesenchymal stem cell , biology , stem cell , antigen , cytokine , t cell , medicine , microbiology and biotechnology
Summary Autoimmune inner ear disease is characterized by progressive, bilateral although asymmetric, sensorineural hearing loss. Patients with autoimmune inner ear disease had higher frequencies of interferon‐γ‐producing T cells than did control subjects tested. Human adipose‐derived mesenchymal stem cells (hASCs) were recently found to suppress effector T cells and inflammatory responses and therefore have beneficial effects in various autoimmune diseases. The aim of this study was to examine the immunosuppressive activity of hASCs on autoreactive T cells from the experimental autoimmune hearing loss (EAHL) murine model. Female BALB/c mice underwent β‐tubulin immunization to develop EAHL; mice with EAHL were given hASCs or PBS intraperitoneally once a week for 6 consecutive weeks. Auditory brainstem responses were examined over time. The T helper type 1 (Th1)/Th17‐mediated autoreactive responses were examined by determining the proliferative response and cytokine profile of splenocytes stimulated with β‐tubulin. The frequency of regulatory T (Treg) cells and their suppressive capacity on autoreactive T cells were also determined. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen‐specific Th1/Th17 cells and induced the production of anti‐inflammatory cytokine interleukin‐10 in splenocytes. They also induced the generation of antigen‐specific CD4 + CD25 + Foxp3 + Treg cells with the capacity to suppress autoantigen‐specific T‐cell responses. The experiment demonstrated that hASCs are one of the important regulators of immune tolerance with the capacity to suppress effector T cells and to induce the generation of antigen‐specific Treg cells.