Human Fetal Auditory Stem Cells Can Be Expanded In Vitro and Differentiate Into Functional Auditory Neurons and Hair Cell-Like Cells

Authors

  • Wei Chen,

    1. Centre for Stem Cell Biology, University of Sheffield, Sheffield, United Kingdom
    2. Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    Search for more papers by this author
  • Stuart L. Johnson,

    1. Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    Search for more papers by this author
  • Walter Marcotti,

    1. Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    Search for more papers by this author
  • Peter W. Andrews,

    1. Centre for Stem Cell Biology, University of Sheffield, Sheffield, United Kingdom
    2. Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    Search for more papers by this author
  • Harry D. Moore,

    1. Centre for Stem Cell Biology, University of Sheffield, Sheffield, United Kingdom
    2. Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    Search for more papers by this author
  • Marcelo N. Rivolta

    Corresponding author
    1. Centre for Stem Cell Biology, University of Sheffield, Sheffield, United Kingdom
    2. Department of Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    • Centre for Stem Cell Biology and Department of Biomedical Sciences, University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, UK
    Search for more papers by this author
    • Telephone: 44(0)-114-2222385; Fax: (0)-114-2765413


  • Author contributions: W.C.: collection and/or assembly of data, data analysis, and interpretation; S.L.J. and W.M.: collection, analysis, and interpretation of electrophysiology data, manuscript writing; P.W.A. and H.D.M.: provision of study material and administrative support; M.N.R: conception and design, financial support, collection and/or assembly of data, its analysis and interpretation, manuscript writing, final approval of manuscript.

  • First published online in Stem CellsExpress March 23, 2009

Abstract

In the quest to develop the tools necessary for a cell-based therapy for deafness, a critical step is to identify a suitable stem cell population. Moreover, the lack of a self-renovating model system for the study of cell fate determination in the human cochlea has impaired our understanding of the molecular events involved in normal human auditory development. We describe here the identification and isolation of a population of SOX2+OCT4+ human auditory stem cells from 9-week-old to 11-week-old fetal cochleae (hFASCs). These cells underwent long-term expansion in vitro and retained their capacity to differentiate into sensory hair cells and neurons, whose functional and electrophysiological properties closely resembled their in vivo counterparts during development. hFASCs, and the differentiating protocols defined here, could be used to study developing human cochlear neurons and hair cells, as models for drug screening and toxicity and may facilitate the development of cell-based therapies for deafness. STEM Cells 2009;27:1196–1204

Ancillary