Adipose tissue-derived mesenchymal stem cells ameliorate experimental autoimmune hearing loss

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.