No abstract

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.

No abstract

No abstract

Objective Autoimmune inner ear disease (AIED) is characterized by progressive, bilateral although asymmetric, and sensorineural hearing loss; there are no specific therapeutic strategies to treat AIED. However, human adipose-derived mesenchymal stem cells (hASCs) are a promising approach for the treatment of autoimmune diseases due to their immune modulatory effects and regenerative potential. Methods BALB/c mice underwent β-tubulin immunization to develop EAHL; and then administered hASCs or PBS intraperitoneally once a week for 6 consecutive weeks. Results Systemic infusion of hASCs significantly improved hearing function in established EAHL. hASCs decreased the proliferation of antigen-specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine IL-10. hASCs also induced the generation of antigen-specific CD4+CD25+Foxp3+ Treg cells, with the capacity to suppress autoantigen-specific T cell responses. Moreover, we tested the presence of HLA-ABC by confocal analysis found that hASCs migrated to inner ear including the stris vascularis and spiral ligament. By histology, we confirmed that hASCs treatment correlated with the repair process of morphological recovery in the inner ear, while the cochlea of control mice remained seriously damaged. Conclusion We show that hASCs have therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response of EAHL as well as by inducing repair of cochlea in animals with established disease.