{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:08:43Z","timestamp":1768345723423,"version":"3.49.0"},"reference-count":177,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovenian Research Agency (Javna Agencija za Raziskovalno Dejavnost RS)","award":["P4\u20130116"],"award-info":[{"award-number":["P4\u20130116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hearing loss is the most prevalent sensorineural impairment in humans. Yet despite very active research, no effective therapy other than the cochlear implant has reached the clinic. Main reasons for this failure are the multifactorial nature of the disorder, its heterogeneity, and a late onset that hinders the identification of etiological factors. Another problem is the lack of human samples such that practically all the work has been conducted on animals. Although highly valuable data have been obtained from such models, there is the risk that inter-species differences exist that may compromise the relevance of the gathered data. Human-based models are therefore direly needed. The irruption of human induced pluripotent stem cell technologies in the field of hearing research offers the possibility to generate an array of otic cell models of human origin; these may enable the identification of guiding signalling cues during inner ear development and of the mechanisms that lead from genetic alterations to pathology. These models will also be extremely valuable when conducting ototoxicity analyses and when exploring new avenues towards regeneration in the inner ear. This review summarises some of the work that has already been conducted with these cells and contemplates future possibilities.<\/jats:p>","DOI":"10.3390\/cells11203331","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"3331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-0591","authenticated-orcid":false,"given":"Mar\u00eda Beatriz","family":"Dur\u00e1n-Alonso","sequence":"first","affiliation":[{"name":"Unit of Excellence, Institute of Biology and Molecular Genetics (IBGM), University of Valladolid-CSIC, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrvoje","family":"Petkovi\u0107","sequence":"additional","affiliation":[{"name":"Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41467-017-00595-4","article-title":"A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction","volume":"8","author":"Bowl","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ingham, N.J., Pearson, S.A., Vancollie, V.E., Rook, V., Lewis, M.A., Chen, J., Buniello, A., Martelletti, E., Preite, L., and Lam, C.C. (2019). Mouse screen reveals multiple new genes underlying mouse and human hearing loss. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000194"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1038\/s41598-019-38634-3","article-title":"Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use","volume":"9","author":"Ishikawa","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Delmaghani, S., and El-Amraoui, A. (2020). Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072309"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103736","DOI":"10.1016\/j.mcn.2022.103736","article-title":"In vitro and in vivo models: What have we learnt about inner ear regeneration and treatment for hearing loss?","volume":"120","author":"Lee","year":"2022","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.21037\/atm-21-2508","article-title":"Experimental animal models of drug-induced sensorineural hearing loss: A narrative review","volume":"9","author":"Lin","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrd4662","article-title":"Assessing drug safety in human tissues\u2014What are the barriers?","volume":"14","author":"Holmes","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10162-016-0589-1","article-title":"Application of Mouse Models to Research in Hearing and Balance","volume":"17","author":"Ohlemiller","year":"2016","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e19763","DOI":"10.1097\/MD.0000000000019763","article-title":"A phase I\/IIa double blind single institute trial of low dose sirolimus for Pendred syndrome\/DFNB4","volume":"99","author":"Fujioka","year":"2020","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lu, Y.-C., Wu, C.-C., Yang, T.-H., Lin, Y.-H., Yu, I.-S., Lin, S.-W., Chang, Q., Lin, X., Wong, J.-M., and Hsu, C.-J. (2013). Differences in the Pathogenicity of the p.H723R Mutation of the Common Deafness-Associated SLC26A4 Gene in Humans and Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064906"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1006\/dbio.2000.0148","article-title":"Connexin31-Deficiency in Mice Causes Transient Placental Dysmorphogenesis but Does Not Impair Hearing and Skin Differentiation","volume":"231","author":"Plum","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1258\/la.2009.009046","article-title":"Comparison of different aminoglycoside antibiotic treatments to refine ototoxicity studies in adult mice","volume":"44","author":"Contreras","year":"2010","journal-title":"Lab. Anim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.toxlet.2009.12.003","article-title":"Ototoxic drugs: Difference in sensitivity between mice and guinea pigs","volume":"193","author":"Poirrier","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Owens, K.N., Santos, F., Roberts, B., Linbo, T., Coffin, A.B., Knisely, A.J., Simon, J.A., Rubel, E.W., and Raible, D.W. (2008). Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000020"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1080\/01677063.2017.1342246","article-title":"The genetics of hair-cell function in zebrafish","volume":"31","author":"Nicolson","year":"2017","journal-title":"J. Neurogenet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10162-021-00798-z","article-title":"How Zebrafish Can Drive the Future of Genetic-based Hearing and Balance Research","volume":"22","author":"Sheets","year":"2021","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s10162-008-0118-y","article-title":"Using the Zebrafish Lateral Line to Screen for Ototoxicity","volume":"9","author":"Chiu","year":"2008","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1021\/acs.jmedchem.7b00932","article-title":"Phenotypic Optimization of Urea\u2013Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss","volume":"61","author":"Chowdhury","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1055\/s-0041-1728677","article-title":"Advancements in Stem Cell Technology and Organoids for the Restoration of Sensorineural Hearing Loss","volume":"32","author":"Bergman","year":"2021","journal-title":"J. Am. Acad. Audiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00439-021-02325-9","article-title":"Deafness-in-a-dish: Modeling hereditary deafness with inner ear organoids","volume":"141","author":"Romano","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/febs.15341","article-title":"The common marmoset as suitable nonhuman alternative for the analysis of primate cochlear development","volume":"288","author":"Hosoya","year":"2021","journal-title":"FEBS J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/dneu.22850","article-title":"Neuronal development in the cochlea of a nonhuman primate model, the common marmoset","volume":"81","author":"Hosoya","year":"2021","journal-title":"Dev. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fnana.2019.00060","article-title":"Anatomical and surgical evaluation of the common marmoset as an animal model in hearing research Front","volume":"13","author":"Kurihara","year":"2019","journal-title":"Neuroanat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13064-022-00162-8","article-title":"Early development of the cochlea of the common marmoset, a non-human primate model","volume":"17","author":"Hosoya","year":"2022","journal-title":"Neural Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22250","DOI":"10.1038\/srep22250","article-title":"Distinct Expression Patterns Of Causative Genes Responsible For Hereditary Progressive Hearing Loss In Non-Human Primate Cochlea","volume":"6","author":"Hosoya","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neulet.2017.10.030","article-title":"Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea","volume":"662","author":"Matsuzaki","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e22931","DOI":"10.1002\/ajp.22931","article-title":"Generation of genetically engineered non-human primate models of brain function and neurological disorders","volume":"81","author":"Park","year":"2019","journal-title":"Am. J. Primatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature08090","article-title":"Generation of transgenic non-human primates with germline transmission","volume":"459","author":"Sasaki","year":"2009","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/stem.3353","article-title":"Human induced pluripotent stem cells and CRISPR\/Cas-mediated targeted genome editing: Platforms to tackle sensorineural hearing loss","volume":"39","author":"Stojkovic","year":"2021","journal-title":"Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nature11415","article-title":"Restoration of auditory evoked responses by human ES-cell-derived otic progenitors","volume":"490","author":"Chen","year":"2012","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nbt.3840","article-title":"Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells","volume":"35","author":"Koehler","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/B978-0-12-822230-0.00008-9","article-title":"Differentiation of inner ear cell types from human-induced pluripotent stem cells for the therapeutic application in sensorineural hearing loss","volume":"Volume 4","author":"Hsu","year":"2021","journal-title":"Recent Advances in iPSC-Derived Cell Types"},{"key":"ref_33","first-page":"24","article-title":"Building inner ears: Recent advances and future challenges for in vitro organoid systems","volume":"28","author":"Steinhart","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"637779","DOI":"10.3389\/fcell.2021.637779","article-title":"Single-Cell Sequencing Applications in the Inner Ear","volume":"9","author":"Wu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1038\/s41467-020-16113-y","article-title":"Characterization of the development of the mouse cochlear epithelium at the single cell level","volume":"11","author":"Kolla","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.celrep.2016.12.020","article-title":"Cochlear Cell Modeling Using Disease-Specific iPSCs Unveils a Degenerative Phenotype and Suggests Treatments for Congenital Progressive Hearing Loss","volume":"18","author":"Hosoya","year":"2017","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1093\/hmg\/ddab097","article-title":"Modeling gap junction beta 2 gene-related deafness with human iPSC","volume":"30","author":"Fukunaga","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13495","DOI":"10.1073\/pnas.2334503100","article-title":"Generation of hair cells by stepwise differentiation of embryonic stem cells","volume":"100","author":"Li","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/stem.3315","article-title":"Directed differentiation and direct reprogramming: Applying stem cell technologies to hearing research","volume":"39","author":"Roccio","year":"2021","journal-title":"Stem Cells"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4252\/wjsc.v12.i6.422","article-title":"Stem cell-based approaches: Possible route to hearing restoration?","volume":"12","author":"Alonso","year":"2020","journal-title":"World J. Stem Cells"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00018-018-2950-5","article-title":"Pluripotent stem cell-derived cochlear cells: A challenge in constant progress","volume":"76","author":"Czajkowski","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3692937","DOI":"10.1155\/2020\/3692937","article-title":"Generation of Otic Lineages from Integration-Free Human-Induced Pluripotent Stem Cells Reprogrammed by mRNAs","volume":"2020","author":"Boddy","year":"2020","journal-title":"Stem Cells Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41419-018-0488-y","article-title":"ATOH1\/RFX1\/RFX3 transcription factors facilitate the differentiation and characterisation of inner ear hair cell-like cells from patient-specific induced pluripotent stem cells harbouring A8344G mutation of mitochondrial DNA","volume":"9","author":"Chen","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neulet.2015.05.032","article-title":"Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method","volume":"599","author":"Ohnishi","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lahlou, H., Lopez-Juarez, A., Fontbonne, A., Nivet, E., and Zine, A. (2018). Modeling human early otic sensory cell development with induced pluripotent stem cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198954"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fnmol.2018.00452","article-title":"Enriched Differentiation of Human Otic Sensory Progenitor Cells Derived From Induced Pluripotent Stem Cells","volume":"11","author":"Lahlou","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1089\/biores.2014.0019","article-title":"Directing Human Induced Pluripotent Stem Cells into a Neurosensory Lineage for Auditory Neuron Replacement","volume":"3","author":"Gunewardene","year":"2014","journal-title":"BioResearch Open Access"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1781202","DOI":"10.1155\/2016\/1781202","article-title":"Innervation of Cochlear Hair Cells by Human Induced Pluripotent Stem Cell-Derived Neurons In Vitro","volume":"2016","author":"Gunewardene","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8508","DOI":"10.1073\/pnas.1605537113","article-title":"Single-cell analysis delineates a trajectory toward the human early otic lineage","volume":"113","author":"Ealy","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/stcltm\/szab023","article-title":"Otic Organoids Containing Spiral Ganglion Neuron-like Cells Derived from Human-induced Pluripotent Stem Cells as a Model of Drug-induced Neuropathy","volume":"11","author":"Kurihara","year":"2022","journal-title":"Stem Cells Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fcell.2019.00025","article-title":"Generation of Vestibular Tissue-Like Organoids From Human Pluripotent Stem Cells Using the Rotary Cell Culture System","volume":"7","author":"Mattei","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/s41419-018-0967-1","article-title":"Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells","volume":"9","author":"Jeong","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.cell.2010.03.035","article-title":"Mechanosensitive Hair Cell-like Cells from Embryonic and Induced Pluripotent Stem Cells","volume":"141","author":"Oshima","year":"2010","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1089\/scd.2014.0033","article-title":"Inner Ear Hair Cell-Like Cells from Human Embryonic Stem Cells","volume":"23","author":"Ronaghi","year":"2014","journal-title":"Stem Cells Dev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Taura, A., Ohnishi, H., Ochi, S., Ebisu, F., Nakagawa, T., and Ito, J. (2014). Effects of mouse utricle stromal tissues on hair cell induction from induced pluripotent stem cells. BMC Neurosci., 15.","DOI":"10.1186\/s12868-014-0121-7"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.reth.2022.04.008","article-title":"Critical roles of FGF, RA, and WNT signalling in the development of the human otic placode and subsequent lineages in a dish","volume":"20","author":"Saeki","year":"2022","journal-title":"Regen. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1242\/dev.119149","article-title":"Generation of sensory hair cells by genetic programming with a combination of transcription factors","volume":"142","author":"Costa","year":"2015","journal-title":"Development"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/stem.62","article-title":"Human Fetal Auditory Stem Cells Can Be Expanded In Vitro and Differentiate Into Functional Auditory Neurons and Hair Cell-Like Cells","volume":"27","author":"Chen","year":"2009","journal-title":"Stem Cells"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"561","DOI":"10.5966\/sctm.2015-0252","article-title":"Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells","volume":"5","author":"Tang","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/cdd.2016.16","article-title":"Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation","volume":"23","author":"Chen","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_61","first-page":"121","article-title":"Neural crest stem cells and their potential application in a therapy for deafness","volume":"4","author":"Margriet","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e136046","DOI":"10.1172\/jci.insight.136046","article-title":"Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss","volume":"5","author":"Cui","year":"2020","journal-title":"JCI Insight"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"DeJonge, R.E., Liu, X.-P., Deig, C.R., Heller, S., Koehler, K.R., and Hashino, E. (2016). Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162508"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11508","DOI":"10.1038\/ncomms11508","article-title":"Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells","volume":"7","author":"Liu","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/nprot.2014.100","article-title":"3D mouse embryonic stem cell culture for generating inner ear organoids","volume":"9","author":"Koehler","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.stemcr.2019.05.014","article-title":"Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids","volume":"13","author":"Tang","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/ar.24067","article-title":"Building an Artificial Stem Cell Niche: Prerequisites for Future 3D-Formation of Inner Ear Structures\u2014Toward 3D Inner Ear Biotechnology","volume":"303","author":"Sliedregt","year":"2020","journal-title":"Anat. Rec."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"102290","DOI":"10.1016\/j.scr.2021.102290","article-title":"Generation of two iPSC lines from siblings of a homozygous patient with hearing loss and a heterozygous carrier with normal hearing carrying p.G45E\/Y136X mutation in GJB2","volume":"53","author":"Fukunaga","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"720858","DOI":"10.3389\/fcell.2021.720858","article-title":"A Model of Waardenburg Syndrome Using Patient-Derived iPSCs With a SOX10 Mutation Displays Compromised Maturation and Function of the Neural Crest That Involves Inner Ear Development","volume":"9","author":"Wen","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s43856-021-00044-w","article-title":"Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction","volume":"1","author":"Jeong","year":"2021","journal-title":"Commun. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e139171","DOI":"10.1172\/jci.insight.139171","article-title":"Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration","volume":"6","author":"Wakizono","year":"2021","journal-title":"JCI Insight"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.heares.2018.11.005","article-title":"Neural crest contributions to the ear: Implications for congenital hearing disorders","volume":"376","author":"Ritter","year":"2018","journal-title":"Hear. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mrrev.2012.11.001","article-title":"Contribution of genetic factors to noise-induced hearing loss: A human studies review","volume":"752","author":"Pawelczyk","year":"2013","journal-title":"Mutat. Res. Mutat. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.heares.2012.08.016","article-title":"GRM7 variants associated with age-related hearing loss based on auditory perception","volume":"294","author":"Newman","year":"2012","journal-title":"Hear. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.heares.2019.01.003","article-title":"Hereditary hearing loss; about the known and the unknown","volume":"376","author":"Kremer","year":"2019","journal-title":"Hear. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6S","DOI":"10.1177\/0003489415575549","article-title":"Gene Expression Profiles of the Cochlea and Vestibular Endorgans: Localization and function of genes causing deafness","volume":"124","author":"Nishio","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/lio2.633","article-title":"Milestones toward cochlear gene therapy for patients with hereditary hearing loss","volume":"6","author":"Yoshimura","year":"2021","journal-title":"Laryngoscope"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"107858","DOI":"10.1016\/j.heares.2019.107858","article-title":"Gene therapy for genetic mutations affecting non-sensory cells in the cochlea","volume":"394","author":"Zhang","year":"2020","journal-title":"Hear. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.devcel.2017.09.026","article-title":"ESRP1 Mutations Cause Hearing Loss due to Defects in Alternative Splicing that Disrupt Cochlear Development","volume":"43","author":"Rohacek","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1017\/S001667231500004X","article-title":"Whole-exome sequencing and its impact in hereditary hearing loss","volume":"97","author":"Atik","year":"2015","journal-title":"Genet. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3389\/fnmol.2017.00428","article-title":"DFNB1 non-syndromic hearing impairment: Diversity of mutations and associated phenotypes","volume":"10","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_82","first-page":"4213","article-title":"Long-range cis-regulatory elements controlling GDF6 expression are essential for ear development","volume":"130","author":"Bademci","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00439-021-02324-w","article-title":"Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2","volume":"141","author":"Stemerdink","year":"2021","journal-title":"Human Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41467-018-08264-w","article-title":"Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders","volume":"10","author":"Pan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"eaay9101","DOI":"10.1126\/scitranslmed.aay9101","article-title":"In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness","volume":"12","author":"Yeh","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"107785","DOI":"10.1016\/j.heares.2019.107785","article-title":"Cochlear histopathology in human genetic hearing loss: State of the science and future prospects","volume":"382","author":"Bommakanti","year":"2019","journal-title":"Hear. Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hu, C.-J., Lu, Y.-C., Yang, T.-H., Chan, Y.-H., Tsai, C.-Y., Yu, I.-S., Lin, S.-W., Liu, T.-C., Cheng, Y.-F., and Wu, C.-C. (2021). Toward the Pathogenicity of the SLC26A4 p.C565Y Variant Using a Genetically Driven Mouse Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062789"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1177\/0300060519829990","article-title":"Efficient introduction of an isogenic homozygous mutation to induced pluripotent stem cells from a hereditary hearing loss family using CRISPR\/Cas9 and single-stranded donor oligonucleotides","volume":"47","author":"Dong","year":"2019","journal-title":"J. Int. Med Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"102599","DOI":"10.1016\/j.scr.2021.102599","article-title":"Generation of hiPSC line UMi030-A from an individual with the hearing loss-related GJB2 mutation c.109G > A","volume":"58","author":"Colbert","year":"2022","journal-title":"Stem Cell Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102736","DOI":"10.1016\/j.scr.2022.102736","article-title":"Generation of a gene corrected human isogenic iPSC line (CPGHi001-A-1) from a hearing loss patient with the TMC1 p.M418K mutation using CRISPR\/Cas9","volume":"60","author":"Wang","year":"2022","journal-title":"Stem Cell Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101795","DOI":"10.1016\/j.scr.2020.101795","article-title":"Establishment of an induced pluripotent stem cell (iPSC) line from a 7-year-old male patient with profound hearing loss carrying c.235delC in GJB2 gene","volume":"45","author":"Huang","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"102405","DOI":"10.1016\/j.scr.2021.102405","article-title":"Derivation of iPSC line UMi029-A bearing a hearing-loss associated variant in the SMPX gene","volume":"54","author":"Dykxhoorn","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.scr.2017.10.024","article-title":"Generation of an induced pluripotent stem cell line from a 39-year-old female patient with severe-to-profound non-syndromic sensorineural hearing loss and a A1555G mutation in the mitochondrial MTRNR1 gene","volume":"25","author":"Hsu","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Liu, X., Lillywhite, J., Zhu, W., Huang, Z., Clark, A., Gosstola, N., Maguire, C., Dykxhoorn, D., Chen, Z.-Y., and Yang, J. (2021). Generation and Genetic Correction of USH2A c.2299delG Mutation in Patient-Derived Induced Pluripotent Stem Cells. Genes, 12.","DOI":"10.3390\/genes12060805"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"101982","DOI":"10.1016\/j.scr.2020.101982","article-title":"Generation of a human induced pluripotent stem cell line (CPGHi001-A) from a hearing loss patient with the TMC1 p.M418K mutation","volume":"49","author":"Wang","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/ng848","article-title":"Beethoven, a mouse model for dominant, progressive hearing loss DFNA36","volume":"30","author":"Vreugde","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature25164","article-title":"Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents","volume":"553","author":"Gao","year":"2018","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41591-019-0500-9","article-title":"Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss","volume":"25","author":"Pan","year":"2019","journal-title":"Nat. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"750023","DOI":"10.3389\/fcell.2021.750023","article-title":"SMPX Deficiency Causes Stereocilia Degeneration and Progressive Hearing Loss in CBA\/CaJ Mice","volume":"9","author":"Tu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"102699","DOI":"10.1016\/j.scr.2022.102699","article-title":"Establishment of iPS cell line (KLRMMEi002-A) by reprogramming peripheral blood mononuclear cells from a patient with USH2A-associated Usher syndrome","volume":"60","author":"Liang","year":"2022","journal-title":"Stem Cell Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.scr.2018.11.007","article-title":"Generation of a human iPSC line, INMi002-A, carrying the most prevalent USH2A variant associated with Usher syndrome type 2","volume":"33","author":"Erkilic","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.omtm.2019.11.016","article-title":"Genome Editing in Patient iPSCs Corrects the Most Prevalent USH2A Mutations and Reveals Intriguing Mutant mRNA Expression Profiles","volume":"17","author":"Erkilic","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"565216","DOI":"10.3389\/fgene.2020.565216","article-title":"Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy","volume":"11","author":"Whatley","year":"2020","journal-title":"Front. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"102300","DOI":"10.1016\/j.scr.2021.102300","article-title":"Establishment of an iPSC line (CSUXHi004-A) from a patient with Waardenburg syndrome type I caused by a PAX3 splice mutation","volume":"53","author":"Wen","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"102606","DOI":"10.1016\/j.scr.2021.102606","article-title":"Establishment of an induced pluripotent stem cell line (ZZUPMCi001-A) derived from peripheral blood mononuclear cells in a patient with type 1 Waardenburg syndrome","volume":"57","author":"Wang","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"102376","DOI":"10.1016\/j.scr.2021.102376","article-title":"Generation of a human induced pluripotent stem cell line (CPGHi003-A) from an auditory neuropathy patient with AIFM1 p.R422Q mutation","volume":"53","author":"Li","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1136\/jmedgenet-2014-102961","article-title":"Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder","volume":"52","author":"Zong","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"101910","DOI":"10.1016\/j.scr.2020.101910","article-title":"Generation of two induced pluripotent stem cell lines from PBMCs of siblings carrying c.235delC mutation in the GJB2 gene associated with sensorineural hearing loss","volume":"47","author":"Fukunaga","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"102188","DOI":"10.1016\/j.scr.2021.102188","article-title":"Reprogramming of human peripheral blood mononuclear cell (PBMC) from a patient suffering from hearing loss into iPSC line (SDQLCHi035-A) maintaining compound heterozygous variations in GJB2 gene","volume":"51","author":"Yang","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1172\/JCI67621","article-title":"Assembly of the cochlear gap junction macromolecular complex requires connexin 26","volume":"124","author":"Kamiya","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"102758","DOI":"10.1016\/j.scr.2022.102758","article-title":"Characterization of an induced pluripotent stem cell line (UMi040-A) bearing an auditory neuropathy spectrum disorder-associated variant in TMEM43","volume":"61","author":"Tang","year":"2022","journal-title":"Stem Cell Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e2019681118","DOI":"10.1073\/pnas.2019681118","article-title":"A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder","volume":"118","author":"Jang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/hmg\/10.2.153","article-title":"Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome","volume":"10","author":"Everett","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"101919","DOI":"10.1016\/j.scr.2020.101919","article-title":"An iPSC line (TYWHSTi002-A) derived from a patient with Pendred syndrome caused by compound heterozygous mutations in the SLC26A4 gene","volume":"47","author":"Chen","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"101524","DOI":"10.1016\/j.scr.2019.101524","article-title":"Generation of a human iPS cell line (CGMH.SLC26A4919-2) from a Pendred syndrome patient carrying SLC26A4 c.919-2A>G splice-site mutation","volume":"40","author":"Cheng","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3892\/mmr.2014.2877","article-title":"Association between the mitochondrial DNA 4977 common deletion in the hair shaft and hearing loss in presbycusis","volume":"11","author":"Liu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s42003-021-02224-9","article-title":"The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis","volume":"4","author":"Ivarsdottir","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"459","DOI":"10.2147\/CIA.S123278","article-title":"Association of genetic variations in the mitochondrial DNA control region with presbycusis","volume":"12","author":"Falah","year":"2017","journal-title":"Clin. Interv. Aging"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1093\/hmg\/ddac096","article-title":"Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients","volume":"31","author":"Chen","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1097\/FPC.0000000000000247","article-title":"PharmGKB summary: Very important pharmacogene information for MT-RNR1","volume":"26","author":"Barbarino","year":"2016","journal-title":"Pharmacogenetics Genom."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/cpt.2309","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype","volume":"111","author":"McDermott","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"29621","DOI":"10.1038\/srep29621","article-title":"Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro","volume":"6","author":"He","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"102831","DOI":"10.1016\/j.scr.2022.102831","article-title":"Establishment of an iPSC line (CPGHi005-A) from a patient with Waardenburg syndrome carrying a heterozygous SVA-F retrotransposon insertion into SOX10","volume":"62","author":"Li","year":"2022","journal-title":"Stem Cell Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"102271","DOI":"10.1016\/j.scr.2021.102271","article-title":"Generation of a gene corrected human isogenic iPSC line (CPGHi002-A-1) from a DDOD patient with heterozygous c.1516 C>T mutation in the ATP6V1B2 gene","volume":"53","author":"Gao","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"101986","DOI":"10.1016\/j.scr.2020.101986","article-title":"Establishment of human induced pluripotent stem cell line (CPGHi002-A) from a 10-month-old female patient with DDOD syndrome carrying a heterozygous c.1516 C > T mutation in ATP6V1B2","volume":"48","author":"Gao","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1089\/scd.2017.0158","article-title":"Generation of Human-Induced Pluripotent Stem Cells from Wolfram Syndrome Type 2 Patients Bearing the c.103 + 1G>A CISD2 Mutation for Disease Modeling","volume":"27","author":"Ntai","year":"2018","journal-title":"Stem Cells Dev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101692","DOI":"10.1016\/j.scr.2019.101692","article-title":"Generation of induced pluripotent stem cells MMCi001-A from a Taiwanese hearing loss patient carrying GJB2 pV37I mutation","volume":"42","author":"Lu","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.scr.2018.10.002","article-title":"Generation of induced pluripotent stem cells from a patient with hearing loss carrying GJB2 p.V37I mutation","volume":"33","author":"Chan","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.reth.2018.11.001","article-title":"Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome","volume":"10","author":"Hosoya","year":"2019","journal-title":"Regen. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.heares.2016.02.019","article-title":"HEI-OC1 cells as a model for investigating drug cytotoxicity","volume":"335","author":"Kalinec","year":"2016","journal-title":"Hear. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/978-1-4939-3615-1_22","article-title":"Development of Cell-Based High-Throughput Chemical Screens for Protection Against Cisplatin-Induced Ototoxicity","volume":"1427","author":"Teitz","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"32423","DOI":"10.1073\/pnas.2013065117","article-title":"Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes","volume":"117","author":"Song","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.neulet.2014.09.028","article-title":"Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo","volume":"583","author":"Oishi","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1568414","DOI":"10.1155\/2018\/1568414","article-title":"Ouabain Does Not Induce Selective Spiral Ganglion Cell Degeneration in Guinea Pigs","volume":"2018","author":"Schomann","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/MAO.0000000000000487","article-title":"Identification of Small Molecule Inhibitors of Cisplatin-Induced Hair Cell Death: Results of a 10,000 compound screen in the zebrafish lateral line","volume":"36","author":"Thomas","year":"2015","journal-title":"Otol. Neurotol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1084\/jem.20172246","article-title":"CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss","volume":"215","author":"Teitz","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"107859","DOI":"10.1016\/j.heares.2019.107859","article-title":"Novel insights into inner ear development and regeneration for targeted hearing loss therapies","volume":"397","author":"Roccio","year":"2020","journal-title":"Hear. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"15960","DOI":"10.1038\/srep15960","article-title":"Novel High Content Screen Detects Compounds That Promote Neurite Regeneration from Cochlear Spiral Ganglion Neurons","volume":"5","author":"Whitlon","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/2472630317712220","article-title":"Automated Cell Culture Systems and Their Applications to Human Pluripotent Stem Cell Studies","volume":"23","author":"Daniszewski","year":"2018","journal-title":"SLAS Technol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1177\/1087057117696795","article-title":"Three-Dimensional Cell Cultures in Drug Discovery and Development","volume":"22","author":"Fang","year":"2017","journal-title":"SLAS Discov."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nmeth.3507","article-title":"Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells","volume":"12","author":"Paull","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e55249","DOI":"10.7554\/eLife.55249","article-title":"Generation of inner ear hair cells by direct lineage conversion of primary somatic cells","volume":"9","author":"Menendez","year":"2020","journal-title":"eLife"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1177\/2472555217696797","article-title":"Development of a Modular Automated System for Maintenance and Differentiation of Adherent Human Pluripotent Stem Cells","volume":"22","author":"Crombie","year":"2017","journal-title":"SLAS Discov."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Kusumoto, D., Yuasa, S., and Fukuda, K. (2022). Induced Pluripotent Stem Cell-Based Drug Screening by Use of Artificial Intelligence. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050562"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"104812","DOI":"10.1016\/j.tiv.2020.104812","article-title":"Development of novel in silico prediction model for drug-induced ototoxicity by using na\u00efve Bayes classifier approach","volume":"65","author":"Zhang","year":"2020","journal-title":"Toxicol. Vitr."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/cbdd.13894","article-title":"In silico prediction of drug-induced ototoxicity using machine learning and deep learning methods","volume":"98","author":"Huang","year":"2021","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev-bioeng-092021-042744","article-title":"Derivation and Differentiation of Human Pluripotent Stem Cells in Microfluidic Devices","volume":"24","author":"Luni","year":"2022","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1177\/2472630318783497","article-title":"Full Factorial Microfluidic Designs and Devices for Parallelizing Human Pluripotent Stem Cell Differentiation","volume":"24","author":"Chadly","year":"2019","journal-title":"SLAS Technol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/sctm.16-0032","article-title":"Directed Differentiation of Human Embryonic Stem Cells Toward Placode-Derived Spiral Ganglion-Like Sensory Neurons","volume":"6","author":"Matsuoka","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"803","DOI":"10.4252\/wjsc.v11.i10.803","article-title":"Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis","volume":"11","author":"Kim","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddy186","article-title":"Drug screening for human genetic diseases using iPSC models","volume":"27","author":"Elitt","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s41416-020-01033-x","article-title":"Pre-clinical animal models are poor predictors of human toxicities in phase 1 oncology clinical trials","volume":"123","author":"Atkins","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"275","DOI":"10.14573\/altex.1807041","article-title":"Animal testing and its alternatives\u2014The most important omics is economics","volume":"35","author":"Meigs","year":"2018","journal-title":"ALTEX"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nrd4609","article-title":"An analysis of the attrition of drug candidates from four major pharmaceutical companies","volume":"14","author":"Waring","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"16196","DOI":"10.1073\/pnas.1202352109","article-title":"Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells","volume":"109","author":"Ruiz","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/stmcls\/sxac020","article-title":"Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine","volume":"40","author":"Poetsch","year":"2022","journal-title":"Stem Cells"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.nbd.2016.11.007","article-title":"Epigenetics of cell fate reprogramming and its implications for neurological disorders modelling","volume":"99","author":"Grzybek","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.stem.2013.11.006","article-title":"Human iPSC-based modeling of late-onset disease via progerin-induced aging","volume":"13","author":"Miller","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Chacko, L.J., Lahlou, H., Steinacher, C., Assou, S., Messat, Y., Dud\u00e1s, J., Edge, A., Crespo, B., Crosier, M., and Sergi, C. (2021). Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910849"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1113\/JP277997","article-title":"Gata3 is required for the functional maturation of inner hair cells and their innervation in the mouse cochlea","volume":"597","author":"Bardhan","year":"2019","journal-title":"J. Physiol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Carpena, N.T., Chang, S.-Y., Choi, J.-E., Jung, J.Y., and Lee, M.Y. (2021). Wnt Modulation Enhances Otic Differentiation by Facilitating the Enucleation Process but Develops Unnecessary Cardiac Structures. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910306"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e68714","DOI":"10.7554\/eLife.68714","article-title":"Deep learning detects cardiotoxicity in a high-content screen with induced pluripotent stem cell-derived cardiomyocytes","volume":"10","author":"Grafton","year":"2021","journal-title":"eLife"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3727\/096368911X623907","article-title":"Fates of Murine Pluripotent Stem Cell-Derived Neural Progenitors following Transplantation into Mouse Cochleae","volume":"21","author":"Nishimura","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/mt.2013.292","article-title":"Conditioning the Cochlea to Facilitate Survival and Integration of Exogenous Cells into the Auditory Epithelium","volume":"22","author":"Park","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1038\/s41467-020-16455-7","article-title":"Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards","volume":"11","author":"Martin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.stemcr.2017.02.003","article-title":"Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives","volume":"8","author":"Itakura","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1097\/01.wnr.0000187628.38010.5b","article-title":"Engraftment of embryonic stem cell-derived neurons into the cochlear modiolus","volume":"16","author":"Okano","year":"2005","journal-title":"NeuroReport"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.ymthe.2019.03.018","article-title":"Engraftment of Human Stem Cell-Derived Otic Progenitors in the Damaged Cochlea","volume":"27","author":"Lahlou","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00441-019-03115-6","article-title":"Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear","volume":"379","author":"Chacko","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1038\/s41467-018-06334-7","article-title":"Molecular characterization and prospective isolation of human fetal cochlear hair cell progenitors","volume":"9","author":"Roccio","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"714","DOI":"10.6061\/clinics\/2017(11)11","article-title":"Evidence of progenitor cells in the adult human cochlea: Sphere formation and identification of ABCG2","volume":"72","author":"Lezirovitz","year":"2017","journal-title":"Clinics"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"710159","DOI":"10.3389\/fcell.2021.710159","article-title":"Hair Cell Generation in Cochlear Culture Models Mediated by Novel \u03b3-Secretase Inhibitors","volume":"9","author":"Erni","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/stem.3175","article-title":"Activation of the RhoA-YAP-\u03b2-catenin signaling axis promotes the expansion of inner ear progenitor cells in 3D culture","volume":"38","author":"Xia","year":"2020","journal-title":"Stem Cells"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"869","DOI":"10.15252\/emmm.201707550","article-title":"A genome editing approach to study cancer stem cells in human tumors","volume":"9","author":"Cortina","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/j.stemcr.2021.08.010","article-title":"High-throughput screening on cochlear organoids identifies VEGFR-MEK-TGFB1 signaling promoting hair cell reprogramming","volume":"16","author":"Liu","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"101364","DOI":"10.1016\/j.redox.2019.101364","article-title":"The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways","volume":"28","author":"He","year":"2019","journal-title":"Redox Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/20\/3331\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:00:34Z","timestamp":1760144434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/20\/3331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,21]]},"references-count":177,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11203331"],"URL":"https:\/\/doi.org\/10.3390\/cells11203331","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,21]]}}}