Human fetal auditory stem cells can be expanded in vitro and differentiate into functional auditory neurons and hair cell-like cells.
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.
Chen
Wei
W
Centre for Stem Cell Biology, University of Sheffield, Sheffield, UK.
Johnson
Stuart L
SL
Marcotti
Walter
W
Andrews
Peter W
PW
Moore
Harry D
HD
Rivolta
Marcelo N
MN
D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D053686:Fetal Stem Cells / Q000166:cytology* / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D009474:Neurons / Q000166:cytology* / Q000378:metabolism