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Approaches to Regenerate Hair Cell and Spiral Ganglion Neuron in the Inner Ear

  • Muhammad Waqas
  • Renjie ChaiEmail author
Chapter

Abstract

The cochlear hair cells are the primary sensory structures accountable for interpreting the mechanical sound waves by converting into neural impulses. The degeneration of these sensory hair cells is irreversible in mammals and if severe damage occurs to the HCs, the deficit may result in permanent hearing loss. The present hearing rehabilitation approaches, including hearing aids and cochlear implants, partially restore hearing mechanism; however, the quality of perceived sound does not really match with the normal hearing ear. Therefore, much attention has been paid on developing regenerative therapies such as gene therapy and stem cells therapy to treat the damaged organ of Corti. These therapies are promising to stimulate the mechanism of regeneration/development in hair cells and spiral ganglion neuron, thus to recover deafness. This chapter specifically presents these two strategies and comprehensively explain their current applications to regenerate hair cells and spiral ganglion neurons in the mammalian inner ear.

Keywords

Sensorineural hearing loss Hair cell regeneration Spiral ganglion neuron regeneration Stem cell therapy AAV-based gene therapy Atoh1-based gene therapy 

Abbreviations

AAV

Adeno-associated virus

Ad

Adenovirus

BDNF

Brain-derived neurotrophic factor

GDNF

Glial-derived neurotrophic factor

HCs

Hair cells

iPSCs

Inducible pluripotent stem cells

NT3

Neurotrophin 3

SCs

Supporting cells

SGNs

Spiral ganglion neurons

SNHL

Sensorineural hearing loss

References

  1. 1.
    Hudspeth A (2014) Integrating the active process of hair cells with cochlear function. Nat Rev Neurosci 15(9):600CrossRefPubMedGoogle Scholar
  2. 2.
    Fettiplace R, Hackney CM (2006) The sensory and motor roles of auditory hair cells. Nat Rev Neurosci 7(1):19CrossRefPubMedGoogle Scholar
  3. 3.
    He DZ, Jia S, Dallos P (2004) Mechanoelectrical transduction of adult outer hair cells studied in a gerbil hemicochlea. Nature 429(6993):766CrossRefPubMedGoogle Scholar
  4. 4.
    Avan P, Büki B, Petit C (2013) Auditory distortions: origins and functions. Physiol Rev 93(4):1563–1619CrossRefPubMedGoogle Scholar
  5. 5.
    Moser T, Starr A (2016) Auditory neuropathy—neural and synaptic mechanisms. Nat Rev Neurol 12(3):135–149.  https://doi.org/10.1038/nrneurol.2016.10CrossRefPubMedGoogle Scholar
  6. 6.
    Mcgill TJ, Schuknecht HF (1976) Human cochlear changes in noise induced hearing loss. Laryngoscope 86(9):1293–1302CrossRefPubMedGoogle Scholar
  7. 7.
    Nadol JB Jr, Burgess BJ, Gantz BJ, Coker NJ, Ketten DR, Kos I, Roland JT Jr, Shiao JY, Eddington DK, Montandon P (2001) Histopathology of cochlear implants in humans. Ann Otol Rhinol Laryngol 110(9):883–891CrossRefPubMedGoogle Scholar
  8. 8.
    McHaney V, Thibadoux G, Hayes F, Green A (1983) Hearing loss in children receiving cisplatin chemotherapy. J Pediatr 102(2):314–317CrossRefPubMedGoogle Scholar
  9. 9.
    Rybak LP (1986) Drug ototoxicity. Annu Rev Pharmacol Toxicol 26(1):79–99CrossRefPubMedGoogle Scholar
  10. 10.
    Waqas M, Gao S, Ali MK, Ma Y, Li W (2018) Inner ear hair cell protection in mammals against the noise-induced cochlear damage. Neural Plast 2018:3170801CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss. J Neurosci 29(45):14077–14085CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kujawa SG, Liberman MC (2015) Synaptopathy in the noise-exposed and aging cochlea: primary neural degeneration in acquired sensorineural hearing loss. Hear Res 330:191–199CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    WHO (20 Mar 2019) Deafness and hearing loss report. https://www.who.int/en/news-room/fact-sheets/detail/deafness-and-hearing-loss
  14. 14.
    Tseng CC, Hu LY, Liu ME, Yang AC, Shen CC, Tsai SJ (2016) Risk of depressive disorders following sudden sensorineural hearing loss: a nationwide population-based retrospective cohort study. J Affect Disord 197:94–99.  https://doi.org/10.1016/j.jad.2016.03.020CrossRefPubMedGoogle Scholar
  15. 15.
    Homans NC, Metselaar RM, Dingemanse JG, van der Schroeff MP, Brocaar MP, Wieringa MH, Baatenburg de Jong RJ, Hofman A, Goedegebure A (2017) Prevalence of age-related hearing loss, including sex differences, in older adults in a large cohort study. Laryngoscope 127(3):725–730.  https://doi.org/10.1002/lary.26150CrossRefPubMedGoogle Scholar
  16. 16.
    Goman AM, Reed NS, Lin FR (2017) Addressing estimated hearing loss in adults in 2060. JAMA Otolaryngol Head Neck Surg 143(7):733–734.  https://doi.org/10.1001/jamaoto.2016.4642CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Sun LW, Johnson RD, Langlo CS, Cooper RF, Razeen MM, Russillo MC, Dubra A, Connor TB Jr, Han DP, Pennesi ME, Kay CN, Weinberg DV, Stepien KE, Carroll J (2016) Assessing photoreceptor structure in retinitis Pigmentosa and usher syndrome. Invest Ophthalmol Vis Sci 57(6):2428–2442.  https://doi.org/10.1167/iovs.15-18246CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tomblin JB, Harrison M, Ambrose SE, Walker EA, Oleson JJ, Moeller MP (2015) Language outcomes in young children with mild to severe hearing loss. Ear Hear 36(1):76SCrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bush ALH, Lister JJ, Lin FR, Betz J, Edwards JD (2015) Peripheral hearing and cognition: evidence from the staying keen in later life (SKILL) study. Ear Hear 36(4):395CrossRefPubMedCentralGoogle Scholar
  20. 20.
    Lin FR, Metter EJ, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L (2011) Hearing loss and incident dementia. Arch Neurol 68(2):214–220CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Smith SL, Pichora-Fuller MK (2015) Associations between speech understanding and auditory and visual tests of verbal working memory: effects of linguistic complexity, task, age, and hearing loss. Front Psychol 6:1394PubMedPubMedCentralGoogle Scholar
  22. 22.
    Sprinzl G, Riechelmann H (2010) Current trends in treating hearing loss in elderly people: a review of the technology and treatment options—a mini-review. Gerontology 56(3):351–358CrossRefPubMedGoogle Scholar
  23. 23.
    Hunter CR, Kronenberger WG, Castellanos I, Pisoni DB (2017) Early postimplant speech perception and language skills predict long-term language and neurocognitive outcomes following pediatric cochlear implantation. J Speech Lang Hear Res 60(8):2321–2336.  https://doi.org/10.1044/2017_jslhr-h-16-0152CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Dowell RC, Dettman SJ, Blamey PJ, Barker EJ, Clark GM (2002) Speech perception in children using cochlear implants: prediction of long-term outcomes. Cochlear Implants Int 3(1):1–18CrossRefPubMedGoogle Scholar
  25. 25.
    Huang J, Sheffield B, Lin P, Zeng F-G (2017) Electro-tactile stimulation enhances cochlear implant speech recognition in noise. Sci Rep 7(1):2196CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bruns L, Mürbe D, Hahne A (2016) Understanding music with cochlear implants. Sci Rep 6:32026CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Corwin JT, Cotanche DA (1988) Regeneration of sensory hair cells after acoustic trauma. Science 240(4860):1772–1774CrossRefPubMedGoogle Scholar
  28. 28.
    Ryals BM, Rubel EW (1988) Hair cell regeneration after acoustic trauma in adult Coturnix quail. Science 240(4860):1774–1776CrossRefPubMedGoogle Scholar
  29. 29.
    Cruz RM, Lambert PR, Rubel EW (1987) Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea. Arch Otolaryngol Head Neck Surg 113(10):1058–1062CrossRefPubMedGoogle Scholar
  30. 30.
    Weisleder P, Rubel EW (1992) Hair cell regeneration in the avian vestibular epithelium. Exp Neurol 115(1):2–6CrossRefGoogle Scholar
  31. 31.
    Stone JS, Cotanche DA (2007) Hair cell regeneration in the avian auditory epithelium. Int J Dev Biol 51(6–7):633–647.  https://doi.org/10.1387/ijdb.072408jsCrossRefPubMedGoogle Scholar
  32. 32.
    Soucek S, Michaels L, Frohlich A (1986) Evidence for hair cell degeneration as the primary lesion in hearing loss of the elderly. J Otolaryngol 15(3):175–183PubMedGoogle Scholar
  33. 33.
    Forge A, Li L, Nevill G (1998) Hair cell recovery in the vestibular sensory epithelia of mature guinea pigs. J Comp Neurol 397(1):69–88CrossRefGoogle Scholar
  34. 34.
    Golub JS, Tong L, Ngyuen TB, Hume CR, Palmiter RD, Rubel EW, Stone JS (2012) Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin. J Neurosci 32(43):15093–15105.  https://doi.org/10.1523/jneurosci.1709-12.2012CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kawamoto K, Izumikawa M, Beyer LA, Atkin GM, Raphael Y (2009) Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity. Hear Res 247(1):17–26.  https://doi.org/10.1016/j.heares.2008.08.010CrossRefPubMedGoogle Scholar
  36. 36.
    Lin V, Golub JS, Nguyen TB, Hume CR, Oesterle EC, Stone JS (2011) Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles. J Neurosci 31(43):15329–15339.  https://doi.org/10.1523/jneurosci.2057-11.2011CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Tanyeri H, Lopez I, Honrubia V (1995) Histological evidence for hair cell regeneration after ototoxic cell destruction with local application of gentamicin in the chinchilla crista ampullaris. Hear Res 89(1–2):194–202CrossRefGoogle Scholar
  38. 38.
    Sinkkonen ST, Chai R, Jan TA, Hartman BH, Laske RD, Gahlen F, Sinkkonen W, Cheng AG, Oshima K, Heller S (2011) Intrinsic regenerative potential of murine cochlear supporting cells. Sci Rep 1:26.  https://doi.org/10.1038/srep00026CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Malgrange B, Belachew S, Thiry M, Nguyen L, Rogister B, Alvarez ML, Rigo JM, Van De Water TR, Moonen G, Lefebvre PP (2002) Proliferative generation of mammalian auditory hair cells in culture. Mech Dev 112(1–2):79–88CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Oshima K, Grimm CM, Corrales CE, Senn P, Martinez Monedero R, Geleoc GS, Edge A, Holt JR, Heller S (2007) Differential distribution of stem cells in the auditory and vestibular organs of the inner ear. J Assoc Res Otolaryngol 8(1):18–31.  https://doi.org/10.1007/s10162-006-0058-3CrossRefPubMedGoogle Scholar
  41. 41.
    Oshima K, Senn P, Heller S (2009) Isolation of sphere-forming stem cells from the mouse inner ear. Methods Mol Biol 493:141–162.  https://doi.org/10.1007/978-1-59745-523-7_9CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    White PM, Doetzlhofer A, Lee YS, Groves AK, Segil N (2006) Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 441(7096):984–987.  https://doi.org/10.1038/nature04849CrossRefPubMedGoogle Scholar
  43. 43.
    Li H, Liu H, Heller S (2003) Pluripotent stem cells from the adult mouse inner ear. Nat Med 9(10):1293–1299.  https://doi.org/10.1038/nm925CrossRefPubMedGoogle Scholar
  44. 44.
    Chai R, Xia A, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, Cheng AG (2011) Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. J Assoc Res Otolaryngol 12(4):455–469.  https://doi.org/10.1007/s10162-011-0267-2CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Bramhall NF, Shi F, Arnold K, Hochedlinger K, Edge AS (2014) Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea. Stem Cell Rep 2(3):311–322.  https://doi.org/10.1016/j.stemcr.2014.01.008CrossRefGoogle Scholar
  46. 46.
    Chai R, Kuo B, Wang T, Liaw EJ, Xia A, Jan TA, Liu Z, Taketo MM, Oghalai JS, Nusse R (2012) Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci 109(21):8167–8172CrossRefGoogle Scholar
  47. 47.
    Shi F, Kempfle JS, Edge AS (2012) Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J Neurosci 32(28):9639–9648.  https://doi.org/10.1523/jneurosci.1064-12.2012CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Atkinson PJ, Kim GS, Cheng AG (2018) Direct cellular reprogramming and inner ear regeneration. Expert Opin Biol Ther 19:129.  https://doi.org/10.1080/14712598.2019.1564035CrossRefGoogle Scholar
  49. 49.
    Cox BC, Chai R, Lenoir A, Liu Z, Zhang L, Nguyen D-H, Chalasani K, Steigelman KA, Fang J, Cheng AG (2014) Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development (Cambridge, England) 141(4):816–829CrossRefGoogle Scholar
  50. 50.
    Zhang S, Zhang Y, Yu P, Hu Y, Zhou H, Guo L, Xu X, Zhu X, Waqas M, Qi J, Zhang X, Liu Y, Chen F, Tang M, Qian X, Shi H, Gao X, Chai R (2017) Characterization of Lgr5+ progenitor cell transcriptomes after neomycin injury in the neonatal mouse cochlea. Front Mol Neurosci 10:213.  https://doi.org/10.3389/fnmol.2017.00213CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Cheng C, Guo L, Lu L, Xu X, Zhang S, Gao J, Waqas M, Zhu C, Chen Y, Zhang X, Xuan C, Gao X, Tang M, Chen F, Shi H, Li H, Chai R (2017) Characterization of the transcriptomes of Lgr5+ hair cell progenitors and Lgr5− supporting cells in the mouse cochlea. Front Mol Neurosci 10:122.  https://doi.org/10.3389/fnmol.2017.00122CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Waqas M, Guo L, Zhang S, Chen Y, Zhang X, Wang L, Tang M, Shi H, Bird PI, Li H, Chai R (2016) Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea. Oncotarget 7(27):41123–41141.  https://doi.org/10.18632/oncotarget.8636CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Li W, Wu J, Yang J, Sun S, Chai R, Chen ZY, Li H (2015) Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci U S A 112(1):166–171.  https://doi.org/10.1073/pnas.1415901112CrossRefPubMedGoogle Scholar
  54. 54.
    Ni W, Lin C, Guo L, Wu J, Chen Y, Chai R, Li W, Li H (2016) Extensive supporting cell proliferation and mitotic hair cell generation by in vivo genetic reprogramming in the neonatal mouse cochlea. J Neurosci 36(33):8734–8745.  https://doi.org/10.1523/jneurosci.0060-16.2016CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Zhang Y, Chen Y, Ni W, Guo L, Lu X, Liu L, Li W, Sun S, Wang L, Li H (2015) Dynamic expression of Lgr6 in the developing and mature mouse cochlea. Front Cell Neurosci 9:165.  https://doi.org/10.3389/fncel.2015.00165CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Zhang Y, Guo L, Lu X, Cheng C, Sun S, Li W, Zhao L, Lai C, Zhang S, Yu C, Tang M, Chen Y, Chai R, Li H (2018) Characterization of Lgr6+ cells as an enriched population of hair cell progenitors compared to Lgr5+ cells for hair cell generation in the neonatal mouse cochlea. Front Mol Neurosci 11:147.  https://doi.org/10.3389/fnmol.2018.00147CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Lu X, Sun S, Qi J, Li W, Liu L, Zhang Y, Chen Y, Zhang S, Wang L, Miao D, Chai R, Li H (2016) Bmi1 regulates the proliferation of cochlear supporting cells via the canonical Wnt signaling pathway. Mol Neurobiol 54:1326.  https://doi.org/10.1007/s12035-016-9686-8CrossRefPubMedGoogle Scholar
  58. 58.
    Chen Y, Lu X, Guo L, Ni W, Zhang Y, Zhao L, Wu L, Sun S, Zhang S, Tang M, Li W, Chai R, Li H (2017) Hedgehog signaling promotes the proliferation and subsequent hair cell formation of progenitor cells in the neonatal mouse cochlea. Front Mol Neurosci 10:426.  https://doi.org/10.3389/fnmol.2017.00426CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Chen Q, Quan Y, Wang N, Xie C, Ji Z, He H, Chai R, Li H, Yin S, Chin YE, Wei X, Gao WQ (2017) Inactivation of STAT3 signaling impairs hair cell differentiation in the developing mouse cochlea. Stem Cell Rep 9(1):231–246.  https://doi.org/10.1016/j.stemcr.2017.05.031CrossRefGoogle Scholar
  60. 60.
    Li W, You D, Chen Y, Chai R, Li H (2016) Regeneration of hair cells in the mammalian vestibular system. Front Med 10(2):143–151.  https://doi.org/10.1007/s11684-016-0451-1CrossRefPubMedGoogle Scholar
  61. 61.
    Wang T, Chai R, Kim GS, Pham N, Jansson L, Nguyen DH, Kuo B, May LA, Zuo J, Cunningham LL, Cheng AG (2015) Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Nat Commun 6:6613.  https://doi.org/10.1038/ncomms7613CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Burns JC, Cox BC, Thiede BR, Zuo J, Corwin JT (2012) In vivo proliferative regeneration of balance hair cells in newborn mice. J Neurosci 32(19):6570–6577.  https://doi.org/10.1523/jneurosci.6274-11.2012CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    You D, Guo L, Li W, Sun S, Chen Y, Chai R, Li H (2018) Characterization of Wnt and Notch-responsive Lgr5+ hair cell progenitors in the striolar region of the neonatal mouse utricle. Front Mol Neurosci 11:137.  https://doi.org/10.3389/fnmol.2018.00137CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Wu J, Li W, Lin C, Chen Y, Cheng C, Sun S, Tang M, Chai R, Li H (2016) Co-regulation of the Notch and Wnt signaling pathways promotes supporting cell proliferation and hair cell regeneration in mouse utricles. Sci Rep 6:29418.  https://doi.org/10.1038/srep29418CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Bucks SA, Cox BC, Vlosich BA, Manning JP, Nguyen TB, Stone JS (2017) Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice. Elife 6:e18128.  https://doi.org/10.7554/eLife.18128CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Lee MY, Park YH (2018) Potential of gene and cell therapy for inner ear hair cells. Biomed Res Int 2018:8137614.  https://doi.org/10.1155/2018/8137614CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Mulligan RC (1993) The basic science of gene therapy. Science 260(5110):926–932CrossRefPubMedGoogle Scholar
  68. 68.
    Wang J, Puel JL (2018) Toward cochlear therapies. Physiol Rev 98(4):2477–2522.  https://doi.org/10.1152/physrev.00053.2017CrossRefPubMedGoogle Scholar
  69. 69.
    Ishimoto S, Kawamoto K, Kanzaki S, Raphael Y (2002) Gene transfer into supporting cells of the organ of Corti. Hear Res 173(1–2):187–197CrossRefPubMedGoogle Scholar
  70. 70.
    Kanzaki S (2018) Gene delivery into the inner ear and its clinical implications for hearing and balance. Molecules 23(10):e2507.  https://doi.org/10.3390/molecules23102507CrossRefPubMedGoogle Scholar
  71. 71.
    Sacheli R, Delacroix L, Vandenackerveken P, Nguyen L, Malgrange B (2013) Gene transfer in inner ear cells: a challenging race. Gene Ther 20(3):237–247.  https://doi.org/10.1038/gt.2012.51CrossRefPubMedGoogle Scholar
  72. 72.
    Holley MC (2002) Application of new biological approaches to stimulate sensory repair and protection. Br Med Bull 63:157–169CrossRefPubMedGoogle Scholar
  73. 73.
    Lim ST, Airavaara M, Harvey BK (2010) Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS. Pharmacol Res 61(1):14–26.  https://doi.org/10.1016/j.phrs.2009.10.002CrossRefPubMedGoogle Scholar
  74. 74.
    Shu Y, Tao Y, Wang Z, Tang Y, Li H, Dai P, Gao G, Chen ZY (2016) Identification of adeno-associated viral vectors that target neonatal and adult mammalian inner ear cell subtypes. Hum Gene Ther 27(9):687–699.  https://doi.org/10.1089/hum.2016.053CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Landegger LD, Pan B, Askew C, Wassmer SJ, Gluck SD, Galvin A, Taylor R, Forge A, Stankovic KM, Holt JR, Vandenberghe LH (2017) A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear. Nat Biotechnol 35(3):280–284.  https://doi.org/10.1038/nbt.3781CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Stone IM, Lurie DI, Kelley MW, Poulsen DJ (2005) Adeno-associated virus-mediated gene transfer to hair cells and support cells of the murine cochlea. Mol Ther 11(6):843–848.  https://doi.org/10.1016/j.ymthe.2005.02.005CrossRefPubMedGoogle Scholar
  77. 77.
    Li Duan M, Bordet T, Mezzina M, Kahn A, Ulfendahl M (2002) Adenoviral and adeno-associated viral vector mediated gene transfer in the Guinea pig cochlea. Neuroreport 13(10):1295–1299CrossRefPubMedGoogle Scholar
  78. 78.
    Luebke AE, Foster PK, Muller CD, Peel AL (2001) Cochlear function and transgene expression in the guinea pig cochlea, using adenovirus- and adeno-associated virus-directed gene transfer. Hum Gene Ther 12(7):773–781.  https://doi.org/10.1089/104303401750148702CrossRefPubMedGoogle Scholar
  79. 79.
    Gyorgy B, Sage C, Indzhykulian AA, Scheffer DI, Brisson AR, Tan S, Wu X, Volak A, Mu D, Tamvakologos PI, Li Y, Fitzpatrick Z, Ericsson M, Breakefield XO, Corey DP, Maguire CA (2017) Rescue of hearing by gene delivery to inner-ear hair cells using exosome-associated AAV. Mol Ther 25(2):379–391.  https://doi.org/10.1016/j.ymthe.2016.12.010CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Gu X, Chai R, Guo L, Dong B, Li W, Shu Y, Huang X, Li H (2019) Transduction of adeno-associated virus vectors targeting hair cells and supporting cells in the neonatal mouse cochlea. Front Cell Neurosci 13:8.  https://doi.org/10.3389/fncel.2019.00008CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Oesterle EC, Chien WM, Campbell S, Nellimarla P, Fero ML (2011) p27(Kip1) is required to maintain proliferative quiescence in the adult cochlea and pituitary. Cell Cycle 10(8):1237–1248.  https://doi.org/10.4161/cc.10.8.15301CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Lowenheim H, Furness DN, Kil J, Zinn C, Gultig K, Fero ML, Frost D, Gummer AW, Roberts JM, Rubel EW, Hackney CM, Zenner HP (1999) Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti. Proc Natl Acad Sci U S A 96(7):4084–4088CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Sage C, Huang M, Karimi K, Gutierrez G, Vollrath MA, Zhang DS, Garcia-Anoveros J, Hinds PW, Corwin JT, Corey DP, Chen ZY (2005) Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein. Science 307(5712):1114–1118.  https://doi.org/10.1126/science.1106642CrossRefPubMedGoogle Scholar
  84. 84.
    Cunningham JJ, Levine EM, Zindy F, Goloubeva O, Roussel MF, Smeyne RJ (2002) The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively to control cell cycle exit. Mol Cell Neurosci 19(3):359–374.  https://doi.org/10.1006/mcne.2001.1090CrossRefPubMedGoogle Scholar
  85. 85.
    Jansson L, Kim GS, Cheng AG (2015) Making sense of Wnt signaling-linking hair cell regeneration to development. Front Cell Neurosci 9:66.  https://doi.org/10.3389/fncel.2015.00066CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Waqas M, Zhang S, He Z, Tang M, Chai R (2016) Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea. Front Med 10(3):237–249CrossRefPubMedGoogle Scholar
  87. 87.
    Weber T, Corbett MK, Chow LM, Valentine MB, Baker SJ, Zuo J (2008) Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells. Proc Natl Acad Sci U S A 105(2):781–785.  https://doi.org/10.1073/pnas.0708061105CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Yu Y, Weber T, Yamashita T, Liu Z, Valentine MB, Cox BC, Zuo J (2010) In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice. J Neurosci 30(17):5927–5936.  https://doi.org/10.1523/jneurosci.5989-09.2010CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Chen P, Zindy F, Abdala C, Liu F, Li X, Roussel MF, Segil N (2003) Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nat Cell Biol 5(5):422–426.  https://doi.org/10.1038/ncb976CrossRefPubMedGoogle Scholar
  90. 90.
    Samarajeewa A, Lenz DR, Xie L, Chiang H, Kirchner R, Mulvaney JF, Edge ASB, Dabdoub A (2018) Transcriptional response to Wnt activation regulates the regenerative capacity of the mammalian cochlea. Development 145(23):166579.  https://doi.org/10.1242/dev.166579CrossRefGoogle Scholar
  91. 91.
    Shi F, Hu L, Edge AS (2013) Generation of hair cells in neonatal mice by beta-catenin overexpression in Lgr5-positive cochlear progenitors. Proc Natl Acad Sci U S A 110(34):13851–13856.  https://doi.org/10.1073/pnas.1219952110CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    NIH CTUNLoM (2019) Safety, tolerability and efficacy for CGF166 in patients with unilateral or bilateral severe-to-profound hearing loss. NIH. https://clinicaltrials.gov/ct2/show/NCT02132130
  93. 93.
    Zhong C, Fu Y, Pan W, Yu J, Wang J (2019) Atoh1 and other related key regulators in the development of auditory sensory epithelium in the mammalian inner ear: function and interplay. Dev Biol 446(2):133–141.  https://doi.org/10.1016/j.ydbio.2018.12.025CrossRefPubMedGoogle Scholar
  94. 94.
    Bermingham NA, Hassan BA, Price SD, Vollrath MA, Ben-Arie N, Eatock RA, Bellen HJ, Lysakowski A, Zoghbi HY (1999) Math1: an essential gene for the generation of inner ear hair cells. Science 284(5421):1837–1841CrossRefPubMedGoogle Scholar
  95. 95.
    Woods C, Montcouquiol M, Kelley MW (2004) Math1 regulates development of the sensory epithelium in the mammalian cochlea. Nat Neurosci 7(12):1310–1318.  https://doi.org/10.1038/nn1349CrossRefPubMedGoogle Scholar
  96. 96.
    Zheng JL, Gao WQ (2000) Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears. Nat Neurosci 3(6):580–586.  https://doi.org/10.1038/75753CrossRefPubMedGoogle Scholar
  97. 97.
    Chen Y, Yu H, Zhang Y, Li W, Lu N, Ni W, He Y, Li J, Sun S, Wang Z, Li H (2013) Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult. Sci Rep 3:2996.  https://doi.org/10.1038/srep02996CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Duran Alonso MB, Lopez Hernandez I, de la Fuente MA, Garcia-Sancho J, Giraldez F, Schimmang T (2018) Transcription factor induced conversion of human fibroblasts towards the hair cell lineage. PLoS One 13(7):e0200210.  https://doi.org/10.1371/journal.pone.0200210CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Shou J, Zheng JL, Gao WQ (2003) Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1. Mol Cell Neurosci 23(2):169–179CrossRefPubMedGoogle Scholar
  100. 100.
    Izumikawa M, Minoda R, Kawamoto K, Abrashkin KA, Swiderski DL, Dolan DF, Brough DE, Raphael Y (2005) Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat Med 11(3):271–276.  https://doi.org/10.1038/nm1193CrossRefPubMedGoogle Scholar
  101. 101.
    Gubbels SP, Woessner DW, Mitchell JC, Ricci AJ, Brigande JV (2008) Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature 455(7212):537–541.  https://doi.org/10.1038/nature07265CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Atkinson PJ, Wise AK, Flynn BO, Nayagam BA, Richardson RT (2014) Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs. PLoS One 9(7):e102077.  https://doi.org/10.1371/journal.pone.0102077CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Kraft S, Hsu C, Brough DE, Staecker H (2013) Atoh1 induces auditory hair cell recovery in mice after ototoxic injury. Laryngoscope 123(4):992–999.  https://doi.org/10.1002/lary.22171CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Liu Z, Dearman JA, Cox BC, Walters BJ, Zhang L, Ayrault O, Zindy F, Gan L, Roussel MF, Zuo J (2012) Age-dependent in vivo conversion of mouse cochlear pillar and Deiters’ cells to immature hair cells by Atoh1 ectopic expression. J Neurosci 32(19):6600–6610.  https://doi.org/10.1523/jneurosci.0818-12.2012CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Ono K, Nakagawa T, Kojima K, Matsumoto M, Kawauchi T, Hoshino M, Ito J (2009) Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae. Mol Cell Neurosci 42(4):391–398.  https://doi.org/10.1016/j.mcn.2009.08.011CrossRefPubMedGoogle Scholar
  106. 106.
    Walters BJ, Liu Z, Crabtree M, Coak E, Cox BC, Zuo J (2014) Auditory hair cell-specific deletion of p27Kip1 in postnatal mice promotes cell-autonomous generation of new hair cells and normal hearing. J Neurosci 34(47):15751–15763.  https://doi.org/10.1523/jneurosci.3200-14.2014CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Walters BJ, Coak E, Dearman J, Bailey G, Yamashita T, Kuo B, Zuo J (2017) In vivo interplay between p27(Kip1), GATA3, ATOH1, and POU4F3 converts non-sensory cells to hair cells in adult mice. Cell Rep 19(2):307–320.  https://doi.org/10.1016/j.celrep.2017.03.044CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Mantela J, Jiang Z, Ylikoski J, Fritzsch B, Zacksenhaus E, Pirvola U (2005) The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear. Development (Cambridge, England) 132(10):2377–2388.  https://doi.org/10.1242/dev.01834CrossRefGoogle Scholar
  109. 109.
    Sage C, Huang M, Vollrath MA, Brown MC, Hinds PW, Corey DP, Vetter DE, Chen ZY (2006) Essential role of retinoblastoma protein in mammalian hair cell development and hearing. Proc Natl Acad Sci U S A 103(19):7345–7350.  https://doi.org/10.1073/pnas.0510631103CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Wemeau JL, Kopp P (2017) Pendred syndrome. Best Pract Res Clin Endocrinol Metab 31(2):213–224.  https://doi.org/10.1016/j.beem.2017.04.011CrossRefPubMedGoogle Scholar
  111. 111.
    White JA, Burgess BJ, Hall RD, Nadol JB (2000) Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse. Hear Res 141(1–2):12–18CrossRefPubMedGoogle Scholar
  112. 112.
    Dabdoub A, Nishimura K (2017) Cochlear implants meet regenerative biology: state of the science and future research directions. Otol Neurotol 38(8):e232–e236.  https://doi.org/10.1097/mao.0000000000001407CrossRefPubMedGoogle Scholar
  113. 113.
    Shibata SB, Cortez SR, Beyer LA, Wiler JA, Di Polo A, Pfingst BE, Raphael Y (2010) Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae. Exp Neurol 223(2):464–472.  https://doi.org/10.1016/j.expneurol.2010.01.011CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Suzuki J, Corfas G, Liberman MC (2016) Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure. Sci Rep 6:24907.  https://doi.org/10.1038/srep24907CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Wise AK, Tu T, Atkinson PJ, Flynn BO, Sgro BE, Hume C, O’Leary SJ, Shepherd RK, Richardson RT (2011) The effect of deafness duration on neurotrophin gene therapy for spiral ganglion neuron protection. Hear Res 278(1–2):69–76.  https://doi.org/10.1016/j.heares.2011.04.010CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Waqas M, Sun S, Xuan C, Fang Q, Zhang X, Islam IU, Qi J, Zhang S, Gao X, Tang M, Shi H, Li H, Chai R (2017) Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro. Sci Rep 7(1):3506.  https://doi.org/10.1038/s41598-017-03810-wCrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Treutlein B, Lee QY, Camp JG, Mall M, Koh W, Shariati SA, Sim S, Neff NF, Skotheim JM, Wernig M, Quake SR (2016) Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq. Nature 534(7607):391–395.  https://doi.org/10.1038/nature18323CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Chanda S, Ang CE, Davila J, Pak C, Mall M, Lee QY, Ahlenius H, Jung SW, Sudhof TC, Wernig M (2014) Generation of induced neuronal cells by the single reprogramming factor ASCL1. Stem Cell Rep 3(2):282–296.  https://doi.org/10.1016/j.stemcr.2014.05.020CrossRefGoogle Scholar
  119. 119.
    Noda T, Meas SJ, Nogami J, Amemiya Y, Uchi R, Ohkawa Y, Nishimura K, Dabdoub A (2018) Direct reprogramming of spiral ganglion non-neuronal cells into neurons: toward ameliorating Sensorineural hearing loss by gene therapy. Front Cell Dev Biol 6:16.  https://doi.org/10.3389/fcell.2018.00016CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Meas SJ, Zhang CL, Dabdoub A (2018) Reprogramming glia into neurons in the peripheral auditory system as a solution for Sensorineural hearing loss: lessons from the central nervous system. Front Mol Neurosci 11:77.  https://doi.org/10.3389/fnmol.2018.00077CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Akil O, Blits B, Lustig LR, Leake PA (2019) Virally mediated overexpression of glial-derived Neurotrophic factor elicits age- and dose-dependent neuronal toxicity and hearing loss. Hum Gene Ther 30(1):88–105.  https://doi.org/10.1089/hum.2018.028CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260(5111):1130–1132CrossRefPubMedGoogle Scholar
  123. 123.
    Buj-Bello A, Buchman VL, Horton A, Rosenthal A, Davies AM (1995) GDNF is an age-specific survival factor for sensory and autonomic neurons. Neuron 15(4):821–828CrossRefPubMedGoogle Scholar
  124. 124.
    Trupp M, Ryden M, Jornvall H, Funakoshi H, Timmusk T, Arenas E, Ibanez CF (1995) Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons. J Cell Biol 130(1):137–148.  https://doi.org/10.1083/jcb.130.1.137CrossRefPubMedGoogle Scholar
  125. 125.
    Nosrat CA, Tomac A, Lindqvist E, Lindskog S, Humpel C, Stromberg I, Ebendal T, Hoffer BJ, Olson L (1996) Cellular expression of GDNF mRNA suggests multiple functions inside and outside the nervous system. Cell Tissue Res 286(2):191–207CrossRefPubMedGoogle Scholar
  126. 126.
    Ylikoski J, Pirvola U, Virkkala J, Suvanto P, Liang XQ, Magal E, Altschuler R, Miller JM, Saarma M (1998) Guinea pig auditory neurons are protected by glial cell line-derived growth factor from degeneration after noise trauma. Hear Res 124(1–2):17–26CrossRefPubMedGoogle Scholar
  127. 127.
    Yagi M, Kanzaki S, Kawamoto K, Shin B, Shah PP, Magal E, Sheng J, Raphael Y (2000) Spiral ganglion neurons are protected from degeneration by GDNF gene therapy. J Assoc Res Otolaryngol 1(4):315–325.  https://doi.org/10.1007/s101620010011CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Maruyama J, Miller JM, Ulfendahl M (2008) Glial cell line-derived neurotrophic factor and antioxidants preserve the electrical responsiveness of the spiral ganglion neurons after experimentally induced deafness. Neurobiol Dis 29(1):14–21.  https://doi.org/10.1016/j.nbd.2007.07.026CrossRefPubMedGoogle Scholar
  129. 129.
    Glueckert R, Bitsche M, Miller JM, Zhu Y, Prieskorn DM, Altschuler RA, Schrott-Fischer A (2008) Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor. J Comp Neurol 507(4):1602–1621.  https://doi.org/10.1002/cne.21619CrossRefPubMedGoogle Scholar
  130. 130.
    Parker MA (2011) Biotechnology in the treatment of sensorineural hearing loss: foundations and future of hair cell regeneration. J Speech Lang Hear Res 54(6):1709–1731.  https://doi.org/10.1044/1092-4388(2011/10-0149)CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676.  https://doi.org/10.1016/j.cell.2006.07.024CrossRefPubMedGoogle Scholar
  132. 132.
    Johnson KR, Gagnon LH, Tian C, Longo-Guess CM, Low BE, Wiles MV, Kiernan AE (2018) Deletion of a long-range Dlx5 enhancer disrupts inner ear development in mice. Genetics 208(3):1165–1179.  https://doi.org/10.1534/genetics.117.300447CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Li H, Roblin G, Liu H, Heller S (2003) Generation of hair cells by stepwise differentiation of embryonic stem cells. Proc Natl Acad Sci U S A 100(23):13495–13500.  https://doi.org/10.1073/pnas.2334503100CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Oshima K, Shin K, Diensthuber M, Peng AW, Ricci AJ, Heller S (2010) Mechanosensitive hair cell-like cells from embryonic and induced pluripotent stem cells. Cell 141(4):704–716.  https://doi.org/10.1016/j.cell.2010.03.035CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Ouji Y, Sakagami M, Omori H, Higashiyama S, Kawai N, Kitahara T, Wanaka A, Yoshikawa M (2017) Efficient induction of inner ear hair cell-like cells from mouse ES cells using combination of Math1 transfection and conditioned medium from ST2 stromal cells. Stem Cell Res 23:50–56.  https://doi.org/10.1016/j.scr.2017.06.013CrossRefPubMedGoogle Scholar
  136. 136.
    Koehler KR, Mikosz AM, Molosh AI, Patel D, Hashino E (2013) Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature 500(7461):217–221.  https://doi.org/10.1038/nature12298CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Costa A, Sanchez-Guardado L, Juniat S, Gale JE, Daudet N, Henrique D (2015) Generation of sensory hair cells by genetic programming with a combination of transcription factors. Development (Cambridge, England) 142(11):1948–1959.  https://doi.org/10.1242/dev.119149CrossRefGoogle Scholar
  138. 138.
    Schaefer SA, Higashi AY, Loomis B, Schrepfer T, Wan G, Corfas G, Dressler GR, Duncan RK (2018) From otic induction to hair cell production: Pax2(EGFP) cell line illuminates key stages of development in mouse inner ear organoid model. Stem Cells Dev 27(4):237–251.  https://doi.org/10.1089/scd.2017.0142CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Chen W, Jongkamonwiwat N, Abbas L, Eshtan SJ, Johnson SL, Kuhn S, Milo M, Thurlow JK, Andrews PW, Marcotti W, Moore HD, Rivolta MN (2012) Restoration of auditory evoked responses by human ES-cell-derived otic progenitors. Nature 490(7419):278–282.  https://doi.org/10.1038/nature11415CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Ronaghi M, Nasr M, Ealy M, Durruthy-Durruthy R, Waldhaus J, Diaz GH, Joubert LM, Oshima K, Heller S (2014) Inner ear hair cell-like cells from human embryonic stem cells. Stem Cells Dev 23(11):1275–1284.  https://doi.org/10.1089/scd.2014.0033CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Chen JR, Tang ZH, Zheng J, Shi HS, Ding J, Qian XD, Zhang C, Chen JL, Wang CC, Li L, Chen JZ, Yin SK, Shao JZ, Huang TS, Chen P, Guan MX, Wang JF (2016) Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation. Cell Death Differ 23(8):1347–1357.  https://doi.org/10.1038/cdd.2016.16CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Tang ZH, Chen JR, Zheng J, Shi HS, Ding J, Qian XD, Zhang C, Chen JL, Wang CC, Li L, Chen JZ, Yin SK, Huang TS, Chen P, Guan MX, Wang JF (2016) 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. Stem Cells Transl Med 5(5):561–571.  https://doi.org/10.5966/sctm.2015-0252CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Koehler KR, Nie J, Longworth-Mills E, Liu XP, Lee J, Holt JR, Hashino E (2017) Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells. Nat Biotechnol 35(6):583–589.  https://doi.org/10.1038/nbt.3840CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Chen J, Hong F, Zhang C, Li L, Wang C, Shi H, Fu Y, Wang J (2018) Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea. Stem Cell Res Ther 9(1):230.  https://doi.org/10.1186/s13287-018-0967-1CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Czajkowski A, Mounier A, Delacroix L, Malgrange B (2019) Pluripotent stem cell-derived cochlear cells: a challenge in constant progress. Cell Mol Life Sci 76(4):627–635.  https://doi.org/10.1007/s00018-018-2950-5CrossRefPubMedGoogle Scholar
  146. 146.
    Takeda H, Dondzillo A, Randall JA, Gubbels SP (2018) Challenges in cell-based therapies for the treatment of hearing loss. Trends Neurosci 41(11):823–837.  https://doi.org/10.1016/j.tins.2018.06.008CrossRefPubMedGoogle Scholar
  147. 147.
    Hildebrand MS, Dahl HH, Hardman J, Coleman B, Shepherd RK, de Silva MG (2005) Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea. J Assoc Res Otolaryngol 6(4):341–354.  https://doi.org/10.1007/s10162-005-0012-9CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Parker MA, Corliss DA, Gray B, Anderson JK, Bobbin RP, Snyder EY, Cotanche DA (2007) Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hear Res 232(1–2):29–43.  https://doi.org/10.1016/j.heares.2007.06.007CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of BiotechnologyFederal Urdu University of Arts, Science and Technology, Gulshan-e-Iqbal CampusKarachiPakistan
  2. 2.MOE Key Laboratory of Developmental Genes and Human DiseaseInstitute of Life Sciences, Southeast UniversityNanjingChina
  3. 3.Co-Innovation Center of Neuroregeneration, Nantong UniversityNantongChina

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