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Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.

Abstract
Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells, is responsible for a substantial proportion of patients with hearing impairment. Although the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss, as poor innervation limits the prospective performance of an implant. Using stem cells to recover the damaged sensory circuitry is a potential therapeutic strategy. Here we present a protocol to induce differentiation from human embryonic stem cells (hESCs) using signals involved in the initial specification of the otic placode. We obtained two types of otic progenitors able to differentiate in vitro into hair-cell-like cells and auditory neurons that display expected electrophysiological properties. Moreover, when transplanted into an auditory neuropathy model, otic neuroprogenitors engraft, differentiate and significantly improve auditory-evoked response thresholds. These results should stimulate further research into the development of a cell-based therapy for deafness.
AuthorsWei Chen, Nopporn Jongkamonwiwat, Leila Abbas, Sarah Jacob Eshtan, Stuart L Johnson, Stephanie Kuhn, Marta Milo, Johanna K Thurlow, Peter W Andrews, Walter Marcotti, Harry D Moore, Marcelo N Rivolta
JournalNature (Nature) Vol. 490 Issue 7419 Pg. 278-82 (Oct 11 2012) ISSN: 1476-4687 [Electronic] England
PMID22972191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • FGF10 protein, human
  • FGF3 protein, human
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 3
Topics
  • Animals
  • Auditory Threshold
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Cochlear Nerve (cytology, physiology)
  • Deafness (chemically induced, therapy)
  • Embryonic Stem Cells (cytology)
  • Evoked Potentials, Auditory
  • Fibroblast Growth Factor 10 (genetics, metabolism)
  • Fibroblast Growth Factor 3 (genetics, metabolism)
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gerbillinae
  • Hair Cells, Auditory (cytology, physiology)
  • Humans
  • Mice
  • Patch-Clamp Techniques
  • Stem Cell Transplantation
  • Stem Cells (cytology)

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