Y.Z. and J.Y. contributed equally to this work.
The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice
Article first published online: 2 MAR 2011
© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd
Volume 133, Issue 1, pages 133–140, May 2011
How to Cite
Zhou, Y., Yuan, J., Zhou, B., Lee, A. J., Lee, A. J., Ghawji Jr, M. and Yoo, T. J. (2011), The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology, 133: 133–140. doi: 10.1111/j.1365-2567.2011.03421.x
- Issue published online: 4 APR 2011
- Article first published online: 2 MAR 2011
- Received 3 September 2010; revised 20 January 2011; accepted 26 January 2011.
- stem cells;
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.