title: 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.
authors.affiliation: Centre for Stem Cell Biology, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Nopporn
authors.initials: N
authors.lastname: Jongkamonwiwat
authors.forename: Leila
authors.initials: L
authors.lastname: Abbas
authors.forename: Sarah Jacob
authors.initials: SJ
authors.lastname: Eshtan
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kuhn
authors.forename: Marta
authors.initials: M
authors.lastname: Milo
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Thurlow
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrews
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
authors.forename: Harry D
authors.initials: HD
authors.lastname: Moore
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Rivolta
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003056:Cochlear Nerve / Q000166:cytology / Q000502:physiology; D003638:Deafness / Q000139:chemically induced / Q000628:therapy; D053595:Embryonic Stem Cells / Q000166:cytology*; D005072:Evoked Potentials, Auditory; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005849:Gerbillinae; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D018408:Patch-Clamp Techniques; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: C496463:FGF10 protein, human; C496444:FGF3 protein, human; D051526:Fibroblast Growth Factor 10; D051518:Fibroblast Growth Factor 3