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Pluripotent stem cells from the adult mouse inner ear

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Abstract

In mammals, the permanence of acquired hearing loss is mostly due to the incapacity of the cochlea to replace lost mechanoreceptor cells, or hair cells. In contrast, damaged vestibular organs can generate new hair cells, albeit in limited numbers. Here we show that the adult utricular sensory epithelium contains cells that display the characteristic features of stem cells. These inner ear stem cells have the capacity for self-renewal, and form spheres that express marker genes of the developing inner ear and the nervous system. Inner ear stem cells are pluripotent and can give rise to a variety of cell types in vitro and in vivo, including cells representative of ectodermal, endodermal and mesodermal lineages. Our observation that these stem cells are capable of differentiating into hair cell–like cells implies a possible use of such cells for the replacement of lost inner-ear sensory cells.

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Figure 1: Utricular sensory epithelial cells form spheres.
Figure 2: Expression of markers by sphere cells and their derivatives.
Figure 3: Sphere-derived cells generate cells with hair-cell characteristics.
Figure 4: Characterization of hair cell–like cells in vitro and in vivo.
Figure 5: Pluripotency of inner-ear stem cells.
Figure 6: Pluripotency of inner-ear stem cells in vivo.

Change history

  • 05 September 2003

    This was incorrect in AOP version but corrected in print. Replaced text as per the note.

Notes

  1. NOTE: In the version of this article initially published online, the Methods section "Isolation of inner ear stem cells" contained an error. The sentence, "We used the growth factors EGF (20 μg/ml of the thymidine analog..." should read, "We used the growth factors EGF (20 ng/ml), IGF-1 (50 ng/ml), basic FGF (10 ng/ml) and LIF (1,000 U/ml; obtained from R&D Systems, Chemicon and Invitrogen, respectively). Spheres were counted after 8 d in culture. Labeling with BrdU was done with 3 μg/ml of the thymidine analog throughout the sphere formation period." This mistake has been corrected for the HTML and print versions of the article.

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Acknowledgements

The authors thank A.J. Hudspeth, A. El Amraoui and C. Petit for generously supplying antibodies; J.E. Johnson for supplying Math-1/nGFP transgenic mice; members of our research group and J.T. Corwin, M. Applebury, J.L. Cyr, A.J. Hudspeth and W.F. Sewell for valuable discussions and suggestions on the manuscript. H.L. is supported in part by the National Nature Science Foundation of China, grant 30271397. This work was supported by grant DC006167 to S.H. from the National Institutes of Health.

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Correspondence to Stefan Heller.

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Li, H., Liu, H. & Heller, S. Pluripotent stem cells from the adult mouse inner ear. Nat Med 9, 1293–1299 (2003). https://doi.org/10.1038/nm925

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