title: The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice.
abstract: 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.
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jingdong
authors.initials: J
authors.lastname: Yuan
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Lee
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Lee
authors.forename: Maher
authors.initials: M
authors.lastname: Ghawji
authors.forename: Tai June
authors.initials: TJ
authors.lastname: Yoo
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002469:Cell Separation; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006312:Hearing Loss, Bilateral / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology