title: The challenge of hair cell regeneration.
abstract: Sensory hair cells of the inner ear are responsible for translating auditory or vestibular stimuli into electrical energy that can be perceived by the nervous system. Although hair cells are exquisitely mechanically sensitive, they can be easily damaged by excessive stimulation by ototoxic drugs and by the effects of aging. In mammals, auditory hair cells are never replaced, such that cumulative damage to the ear causes progressive and permanent deafness. In contrast, non-mammalian vertebrates are capable of replacing lost hair cells, which has led to efforts to understand the molecular and cellular basis of regenerative responses in different vertebrate species. In this review, we describe recent progress in understanding the limits to hair cell regeneration in mammals and discuss the obstacles that currently exist for therapeutic approaches to hair cell replacement.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, BCM 295, 1 Baylor Plaza, Houston, TX 77030, USA. akgroves@bcm.edu
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Groves
mesh_terms: D000818:Animals; D001001:Anura / Q000502:physiology; D001717:Birds / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003051:Cochlea / Q000166:cytology / Q000502:physiology; D005399:Fishes / Q000502:physiology; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007760:Labyrinth Supporting Cells / Q000166:cytology / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology
references.citation: Hear Res. 2008 Jun;240(1-2):52-6
references.pmid: 18430530
references.citation: J Comp Neurol. 2008 Nov 20;511(3):396-414
references.pmid: 18803241
references.citation: Int J Audiol. 2008 Nov;47(11):702-7
references.pmid: 19031229
references.citation: J Neurocytol. 1999 Oct-Nov;28(10-11):863-76
references.pmid: 10900090
references.citation: BMC Dev Biol. 2008 Feb 26;8:20
references.pmid: 18302773
references.citation: Nat Med. 2003 Oct;9(10):1293-9
references.pmid: 12949502
references.citation: Panminerva Med. 2008 Mar;50(1):41-53
references.pmid: 18427387
references.citation: Development. 2005 Oct;132(19):4353-62
references.pmid: 16141228
references.citation: J Assoc Res Otolaryngol. 2008 Jun;9(2):225-40
references.pmid: 18449604
references.citation: J Neurosci. 1995 Apr;15(4):3013-26
references.pmid: 7722642
references.citation: Eur J Neurosci. 2007 Apr;25(8):2307-18
references.pmid: 17445229
references.citation: Mech Dev. 1998 Nov;78(1-2):159-63
references.pmid: 9858718
references.citation: J Assoc Res Otolaryngol. 2005 Dec;6(4):341-54
references.pmid: 16208453
references.citation: Science. 1988 Jun 24;240(4860):1772-4
references.pmid: 3381100
references.citation: J Comp Neurol. 2003 Aug 18;463(2):177-95
references.pmid: 12815755
references.citation: Exp Neurol. 1992 Jan;115(1):44-9
references.pmid: 1728572
references.citation: Development. 1999 Feb;126(5):961-73
references.pmid: 9927597
references.citation: J Neurosci. 2001 Feb 1;21(3):974-82
references.pmid: 11157083
references.citation: Nat Med. 2005 Mar;11(3):271-6
references.pmid: 15711559
references.citation: J Neurobiol. 2006 Mar;66(4):319-31
references.pmid: 16408287
references.citation: Development. 2006 Apr;133(7):1277-86
references.pmid: 16495313
references.citation: Curr Top Dev Biol. 2003;57:449-66
references.pmid: 14674489
references.citation: Drug Discov Today. 2005 Oct 1;10(19):1323-30
references.pmid: 16214677
references.citation: Nat Neurosci. 2000 Jun;3(6):580-6
references.pmid: 10816314
references.citation: Science. 1995 Feb 3;267(5198):701-7
references.pmid: 7839150
references.citation: Cell. 2008 Feb 22;132(4):598-611
references.pmid: 18295578
references.citation: Nat Cell Biol. 2003 May;5(5):422-6
references.pmid: 12717441
references.citation: Semin Cell Dev Biol. 2003 Apr;14(2):113-9
references.pmid: 12651094
references.citation: Exp Neurol. 2006 Mar;198(1):12-24
references.pmid: 16376874
references.citation: J Neurobiol. 2006 Nov;66(13):1489-500
references.pmid: 17013931
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4084-8
references.pmid: 10097167
references.citation: Acta Otolaryngol Suppl. 2004 Mar;(551):48-52
references.pmid: 15078078
references.citation: Development. 2002 May;129(10):2495-505
references.pmid: 11973280
references.citation: Brain Res Bull. 2003 Jun 15;60(5-6):397-422
references.pmid: 12787864
references.citation: J Comp Neurol. 1994 Mar 1;341(1):50-67
references.pmid: 8006223
references.citation: J Neurosci. 2003 Jun 1;23(11):4395-400
references.pmid: 12805278
references.citation: J Neurocytol. 1999 Oct-Nov;28(10-11):925-37
references.pmid: 10900095
references.citation: PLoS Genet. 2006 Jan;2(1):e4
references.pmid: 16410827
references.citation: Curr Med Chem. 2007;14(27):2937-43
references.pmid: 18045139
references.citation: Int J Dev Biol. 2007;51(6-7):571-83
references.pmid: 17891718
references.citation: Nature. 2005 Apr 21;434(7036):1031-5
references.pmid: 15846349
references.citation: Hear Res. 1990 Sep;48(1-2):161-82
references.pmid: 2249958
references.citation: Laryngoscope. 2006 Aug;116(8):1363-7
references.pmid: 16885736
references.citation: Hear Res. 1999 Jul;133(1-2):53-60
references.pmid: 10416864
references.citation: Rev Laryngol Otol Rhinol (Bord). 1993;114(3):171-5
references.pmid: 8191059
references.citation: J Neurosci. 1995 Jun;15(6):4618-28
references.pmid: 7790928
references.citation: Neuroreport. 2003 Sep 15;14(13):1677-81
references.pmid: 14512836
references.citation: Proc Natl Acad Sci U S A. 1985 Jun;82(11):3911-5
references.pmid: 3923484
references.citation: J Comp Neurol. 2000 Jan 31;417(1):1-16
references.pmid: 10660884
references.citation: Neuroreport. 2006 Feb 6;17(2):121-4
references.pmid: 16407756
references.citation: Br Med Bull. 2002;63:25-38
references.pmid: 12324382
references.citation: J Comp Neurol. 1998 Jul 20;397(1):69-88
references.pmid: 9671280
references.citation: Gastroenterology. 2009 Aug;137(2):466-81
references.pmid: 19470389
references.citation: J Neurosci. 1992 Nov;12(11):4565-74
references.pmid: 1432110
references.citation: Exp Neurol. 2005 Jun;193(2):326-33
references.pmid: 15869935
references.citation: Science. 1999 Jun 11;284(5421):1837-41
references.pmid: 10364557
references.citation: Otol Neurotol. 2007 Feb;28(2):223-31
references.pmid: 17255891
references.citation: Development. 2005 May;132(10):2377-88
references.pmid: 15843406
references.citation: Cell Tissue Res. 2008 Sep;333(3):373-9
references.pmid: 18575894
references.citation: BMC Dev Biol. 2007 Oct 12;7:112
references.pmid: 17935626
references.citation: Adv Otorhinolaryngol. 2009;66:64-86
references.pmid: 19494573
references.citation: Eur J Neurosci. 2007 Feb;25(4):985-98
references.pmid: 17331195
references.citation: Science. 2008 Aug 29;321(5893):1218-21
references.pmid: 18669821
references.citation: Hear Res. 2009 Mar;249(1-2):15-22
references.pmid: 19185606
references.citation: Eur J Neurosci. 2007 Mar;25(5):1363-72
references.pmid: 17425563
references.citation: Hear Res. 1997 Nov;113(1-2):117-32
references.pmid: 9387991
references.citation: Audiol Neurootol. 2006;11(6):343-56
references.pmid: 16988498
references.citation: J Cell Physiol. 2003 Mar;194(3):237-55
references.pmid: 12548545
references.citation: Audiol Neurootol. 1999 Nov-Dec;4(6):286-302
references.pmid: 10516389
references.citation: Nat Neurosci. 2009 Jun;12(6):679-85
references.pmid: 19471265
references.citation: Gene Expr Patterns. 2003 Aug;3(4):389-95
references.pmid: 12915300
references.citation: Hear Res. 1992 Jan;57(2):166-74
references.pmid: 1733910
references.citation: J Neurosci Res. 2004 Nov 15;78(4):461-71
references.pmid: 15372572
references.citation: Dev Neurobiol. 2008 Apr;68(5):669-84
references.pmid: 18278797
references.citation: J Mol Med (Berl). 2006 Jan;84(1):37-45
references.pmid: 16283144
references.citation: Otol Neurotol. 2009 Apr;30(3):418-422
references.pmid: 19326501
references.citation: Development. 2000 Nov;127(21):4551-60
references.pmid: 11023859
references.citation: Science. 1992 Mar 27;255(5052):1707-10
references.pmid: 1553558
references.citation: J Comp Neurol. 1998 Sep 28;399(3):413-23
references.pmid: 9733087
references.citation: Otol Neurotol. 2006 Dec;27(8):1146-51
references.pmid: 16885783
references.citation: Development. 1999 Apr;126(8):1581-90
references.pmid: 10079221
references.citation: Nat Genet. 1999 Mar;21(3):289-92
references.pmid: 10080181
references.citation: Physiol Rev. 2001 Jul;81(3):1305-52
references.pmid: 11427697
references.citation: Annu Rev Genet. 2009;43:411-37
references.pmid: 19694516
references.citation: Exp Cell Res. 2005 Jun 10;306(2):309-16
references.pmid: 15925585
references.citation: Dev Biol. 2007 Jul 1;307(1):165-78
references.pmid: 17531970
references.citation: Cell Motil Cytoskeleton. 1991;18(3):215-27
references.pmid: 1711932
references.citation: Science. 1988 Jun 24;240(4860):1774-6
references.pmid: 3381101
references.citation: J Assoc Res Otolaryngol. 2009 Sep;10(3):321-40
references.pmid: 19373512
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):781-5
references.pmid: 18178626
references.citation: Semin Cell Dev Biol. 1998 Dec;9(6):583-9
references.pmid: 9892564
references.citation: J Neurosci Res. 2008 Nov 1;86(14):3075-85
references.pmid: 18543340
references.citation: Acta Otolaryngol Suppl. 2004 Mar;(551):31-3
references.pmid: 15078074
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16675-80
references.pmid: 17895386
references.citation: Dev Cell. 2009 Jan;16(1):58-69
references.pmid: 19154718
references.citation: Arch Histol Cytol. 2006 Dec;69(4):209-25
references.pmid: 17287576
references.citation: Mol Cell Neurosci. 2007 Jan;34(1):59-68
references.pmid: 17113786
references.citation: Hear Res. 2008 Nov;245(1-2):5-17
references.pmid: 18790034
references.citation: Dev Biol. 2008 Apr 1;316(1):87-99
references.pmid: 18291358
references.citation: Cell Transplant. 2008;17(6):665-78
references.pmid: 18819255
references.citation: Dev Dyn. 2005 Jun;233(2):570-83
references.pmid: 15844198
references.citation: Drug Discov Today. 2005 Oct 1;10(19):1307-12
references.pmid: 16214675
references.citation: Int J Dev Biol. 2007;51(6-7):633-47
references.pmid: 17891722
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14206-10
references.pmid: 9391178
references.citation: J Neurosci. 2007 Apr 18;27(16):4313-25
references.pmid: 17442815
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2005 Oct;13(5):294-300
references.pmid: 16160524
references.citation: J Assoc Res Otolaryngol. 2007 Mar;8(1):18-31
references.pmid: 17171473
references.citation: Curr Opin Genet Dev. 2009 Aug;19(4):368-73
references.pmid: 19604683
references.citation: Noise Health. 2003 Jul-Sep;5(20):19-28
references.pmid: 14558889
references.citation: Hear Res. 1987;30(2-3):181-95
references.pmid: 3680064
references.citation: Hear Res. 1984 Aug;15(2):133-42
references.pmid: 6490539
references.citation: Neuroreport. 2005 Sep 28;16(14):1545-9
references.pmid: 16148742
references.citation: Neurosci Lett. 1996 Feb 16;205(1):17-20
references.pmid: 8867010
references.citation: Dev Biol. 2009 Feb 1;326(1):86-100
references.pmid: 19013445
references.citation: Neuron. 1993 Nov;11(5):951-66
references.pmid: 8240816
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18396-401
references.pmid: 19011097
references.citation: Hear Res. 1990 Jun;46(1-2):29-40
references.pmid: 2380125
references.citation: J Assoc Res Otolaryngol. 2007 Jun;8(2):194-204
references.pmid: 17334849
references.citation: Acta Otolaryngol. 2001 Jan;121(2):140-2
references.pmid: 11349765
references.citation: J Neurosci. 2009 May 6;29(18):5711-2
references.pmid: 19420238
references.citation: Naturwissenschaften. 1988 Jun;75(6):319-20
references.pmid: 3205314
references.citation: J Comp Neurol. 2006 Dec 10;499(5):691-701
references.pmid: 17048225
references.citation: Hear Res. 2008 Aug;242(1-2):110-6
references.pmid: 18585449
references.citation: Am J Otol. 1994 Jan;15(1):28-34
references.pmid: 8109626
references.citation: Acta Otolaryngol Suppl. 2004 Mar;(551):53-5
references.pmid: 15078079
references.citation: J Neurosci. 2002 Feb 1;22(3):612-3
references.pmid: 11826087
references.citation: J Neurocytol. 1999 Oct-Nov;28(10-11):809-19
references.pmid: 10900086
references.citation: Audiol Neurootol. 2007;12(6):345-58
references.pmid: 17664866
references.citation: Cell Cycle. 2007 Mar 1;6(5):612-9
references.pmid: 17351334
references.citation: Nature. 2008 Sep 25;455(7212):537-41
references.pmid: 18754012
references.citation: Neuroreport. 2007 Dec 3;18(18):1911-4
references.pmid: 18007185
references.citation: Laryngoscope. 2007 Sep;117(9):1629-35
references.pmid: 17632425
references.citation: Adv Otorhinolaryngol. 2009;66:52-63
references.pmid: 19494572
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13495-500
references.pmid: 14593207
references.citation: BMC Dev Biol. 2005 Aug 17;5:16
references.pmid: 16107213
references.citation: Arch Otolaryngol Head Neck Surg. 1987 Oct;113(10):1058-62
references.pmid: 3620125
references.citation: J Neurosci. 2007 Feb 7;27(6):1434-44
references.pmid: 17287518
references.citation: Science. 1999 Apr 30;284(5415):770-6
references.pmid: 10221902
references.citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7345-50
references.pmid: 16648263
references.citation: Curr Opin Genet Dev. 2006 Oct;16(5):518-24
references.pmid: 16919447
references.citation: J Neurosci. 1990 Aug;10(8):2502-12
references.pmid: 2388077
references.citation: Science. 2000 Feb 25;287(5457):1433-8
references.pmid: 10688783
references.citation: Curr Opin Neurobiol. 2003 Feb;13(1):119-26
references.pmid: 12593990
references.citation: Dev Dyn. 2007 Jan;236(1):156-70
references.pmid: 17096404
references.citation: Am J Otolaryngol. 2009 Jan-Feb;30(1):8-16
references.pmid: 19027507
references.citation: Artif Organs. 2006 Oct;30(10):743-55
references.pmid: 17026573
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3152-5
references.pmid: 7724532
references.citation: Mech Dev. 1999 Jun;84(1-2):169-72
references.pmid: 10473135
references.citation: J Neurosci. 1998 Oct 1;18(19):7811-21
references.pmid: 9742150
references.citation: Development. 2000 Aug;127(15):3373-83
references.pmid: 10887092
references.citation: Science. 1995 Feb 3;267(5198):707-11
references.pmid: 7839151
references.citation: Development. 2004 Mar;131(5):965-73
references.pmid: 14973298
references.citation: Hear Res. 1990 Jul;46(3):229-37
references.pmid: 2394635
references.citation: Int J Dev Biol. 2007;51(6-7):463-72
references.pmid: 17891709
references.citation: Exp Cell Res. 2005 Jan 1;302(1):40-7
references.pmid: 15541724
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):8-9
references.pmid: 19118205
references.citation: Am J Pathol. 2007 Jul;171(1):214-26
references.pmid: 17591967
references.citation: Hear Res. 1997 Nov;113(1-2):14-28
references.pmid: 9387983
references.citation: Ann N Y Acad Sci. 2009 Jul;1170:28-33
references.pmid: 19686102
references.citation: Hear Res. 2007 Oct;232(1-2):29-43
references.pmid: 17659854
references.citation: Nature. 2006 Jun 22;441(7096):984-7
references.pmid: 16791196
references.citation: Oncogene. 2001 Dec 20;20(58):8342-57
references.pmid: 11840327
references.citation: Development. 2006 Aug;133(15):2817-26
references.pmid: 16790479
references.citation: Science. 2005 Feb 18;307(5712):1114-8
references.pmid: 15653467
references.citation: J Comp Neurol. 1981 Oct 1;201(4):541-53
references.pmid: 7287934
references.citation: Science. 1993 Mar 12;259(5101):1616-9
references.pmid: 8456284
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):21000-5
references.pmid: 19064919
references.citation: Ciba Found Symp. 1991;160:25-39; discussion 40-53
references.pmid: 1752167
references.citation: Acta Otolaryngol Suppl. 2004 Mar;(551):65-8
references.pmid: 15078082
references.citation: Annu Rev Cell Dev Biol. 2009;25:253-75
references.pmid: 19575663
references.citation: Nat Neurosci. 2004 Dec;7(12):1310-8
references.pmid: 15543141
references.citation: Int J Dev Biol. 2007;51(6-7):447-61
references.pmid: 17891708
references.citation: J Assoc Res Otolaryngol. 2000 Sep;1(2):161-71
references.pmid: 11545143
references.citation: J Assoc Res Otolaryngol. 2009 Jun;10(2):173-90
references.pmid: 19247714
references.citation: J Neurosci. 2001 Jul 1;21(13):4712-20
references.pmid: 11425898
references.citation: Exp Neurol. 2001 May;169(1):30-5
references.pmid: 11312555
references.citation: Eur J Neurosci. 2007 Dec;26(11):3016-23
references.pmid: 18005071
references.citation: J Assoc Res Otolaryngol. 2003 Sep;4(3):422-43
references.pmid: 14690060
references.citation: J Clin Invest. 2000 Jun;105(11):1493-9
references.pmid: 10841502
references.citation: Hear Res. 2006 Apr;214(1-2):28-36
references.pmid: 16513305
references.citation: J Comp Neurol. 1993 May 1;331(1):75-96
references.pmid: 8320349
references.citation: Ann Otol Rhinol Laryngol. 1989 Jun;98(6):411-6
references.pmid: 2729822
references.citation: Int J Dev Biol. 2007;51(6-7):649-54
references.pmid: 17891723
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2008 Oct;16(5):465-71
references.pmid: 18797290
references.citation: Hear Res. 1991 Feb;51(2):173-83
references.pmid: 1709631
references.citation: Science. 1993 Mar 12;259(5101):1619-22
references.pmid: 8456285
references.citation: J Neurosci. 2001 Jan 15;21(2):570-80
references.pmid: 11160436
references.citation: Cell Transplant. 2006;15(5):369-80
references.pmid: 16970279
references.citation: Nat Rev Neurosci. 2006 Nov;7(11):837-49
references.pmid: 17053809
references.citation: Int J Dev Biol. 2007;51(6-7):585-95
references.pmid: 17891719
references.citation: Brain Res. 2006 May 26;1091(1):172-85
references.pmid: 16626654
references.citation: Curr Opin Neurobiol. 2008 Aug;18(4):377-82
references.pmid: 18929656