The challenge of hair cell regeneration.
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.
Groves
Andrew K
AK
Department of Neuroscience, Baylor College of Medicine, BCM 295, 1 Baylor Plaza, Houston, TX 77030, USA. akgroves@bcm.edu
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
Hear Res. 2008 Jun;240(1-2):52-6
18430530
J Comp Neurol. 2008 Nov 20;511(3):396-414
18803241
Int J Audiol. 2008 Nov;47(11):702-7
19031229
J Neurocytol. 1999 Oct-Nov;28(10-11):863-76
10900090
BMC Dev Biol. 2008 Feb 26;8:20
18302773
Nat Med. 2003 Oct;9(10):1293-9
12949502
Panminerva Med. 2008 Mar;50(1):41-53
18427387
Development. 2005 Oct;132(19):4353-62
16141228
J Assoc Res Otolaryngol. 2008 Jun;9(2):225-40
18449604
J Neurosci. 1995 Apr;15(4):3013-26
7722642
Eur J Neurosci. 2007 Apr;25(8):2307-18
17445229
Mech Dev. 1998 Nov;78(1-2):159-63
9858718
J Assoc Res Otolaryngol. 2005 Dec;6(4):341-54
16208453
Science. 1988 Jun 24;240(4860):1772-4
3381100
J Comp Neurol. 2003 Aug 18;463(2):177-95
12815755
Exp Neurol. 1992 Jan;115(1):44-9
1728572
Development. 1999 Feb;126(5):961-73
9927597
J Neurosci. 2001 Feb 1;21(3):974-82
11157083
Nat Med. 2005 Mar;11(3):271-6
15711559
J Neurobiol. 2006 Mar;66(4):319-31
16408287
Development. 2006 Apr;133(7):1277-86
16495313
Curr Top Dev Biol. 2003;57:449-66
14674489
Drug Discov Today. 2005 Oct 1;10(19):1323-30
16214677
Nat Neurosci. 2000 Jun;3(6):580-6
10816314
Science. 1995 Feb 3;267(5198):701-7
7839150
Cell. 2008 Feb 22;132(4):598-611
18295578
Nat Cell Biol. 2003 May;5(5):422-6
12717441
Semin Cell Dev Biol. 2003 Apr;14(2):113-9
12651094
Exp Neurol. 2006 Mar;198(1):12-24
16376874
J Neurobiol. 2006 Nov;66(13):1489-500
17013931
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4084-8
10097167
Acta Otolaryngol Suppl. 2004 Mar;(551):48-52
15078078
Development. 2002 May;129(10):2495-505
11973280
Brain Res Bull. 2003 Jun 15;60(5-6):397-422
12787864
J Comp Neurol. 1994 Mar 1;341(1):50-67
8006223
J Neurosci. 2003 Jun 1;23(11):4395-400
12805278
J Neurocytol. 1999 Oct-Nov;28(10-11):925-37
10900095
PLoS Genet. 2006 Jan;2(1):e4
16410827
Curr Med Chem. 2007;14(27):2937-43
18045139
Int J Dev Biol. 2007;51(6-7):571-83
17891718
Nature. 2005 Apr 21;434(7036):1031-5
15846349
Hear Res. 1990 Sep;48(1-2):161-82
2249958
Laryngoscope. 2006 Aug;116(8):1363-7
16885736
Hear Res. 1999 Jul;133(1-2):53-60
10416864
Rev Laryngol Otol Rhinol (Bord). 1993;114(3):171-5
8191059
J Neurosci. 1995 Jun;15(6):4618-28
7790928
Neuroreport. 2003 Sep 15;14(13):1677-81
14512836
Proc Natl Acad Sci U S A. 1985 Jun;82(11):3911-5
3923484
J Comp Neurol. 2000 Jan 31;417(1):1-16
10660884
Neuroreport. 2006 Feb 6;17(2):121-4
16407756
Br Med Bull. 2002;63:25-38
12324382
J Comp Neurol. 1998 Jul 20;397(1):69-88
9671280
Gastroenterology. 2009 Aug;137(2):466-81
19470389
J Neurosci. 1992 Nov;12(11):4565-74
1432110
Exp Neurol. 2005 Jun;193(2):326-33
15869935
Science. 1999 Jun 11;284(5421):1837-41
10364557
Otol Neurotol. 2007 Feb;28(2):223-31
17255891
Development. 2005 May;132(10):2377-88
15843406
Cell Tissue Res. 2008 Sep;333(3):373-9
18575894
BMC Dev Biol. 2007 Oct 12;7:112
17935626
Adv Otorhinolaryngol. 2009;66:64-86
19494573
Eur J Neurosci. 2007 Feb;25(4):985-98
17331195
Science. 2008 Aug 29;321(5893):1218-21
18669821
Hear Res. 2009 Mar;249(1-2):15-22
19185606
Eur J Neurosci. 2007 Mar;25(5):1363-72
17425563
Hear Res. 1997 Nov;113(1-2):117-32
9387991
Audiol Neurootol. 2006;11(6):343-56
16988498
J Cell Physiol. 2003 Mar;194(3):237-55
12548545
Audiol Neurootol. 1999 Nov-Dec;4(6):286-302
10516389
Nat Neurosci. 2009 Jun;12(6):679-85
19471265
Gene Expr Patterns. 2003 Aug;3(4):389-95
12915300
Hear Res. 1992 Jan;57(2):166-74
1733910
J Neurosci Res. 2004 Nov 15;78(4):461-71
15372572
Dev Neurobiol. 2008 Apr;68(5):669-84
18278797
J Mol Med (Berl). 2006 Jan;84(1):37-45
16283144
Otol Neurotol. 2009 Apr;30(3):418-422
19326501
Development. 2000 Nov;127(21):4551-60
11023859
Science. 1992 Mar 27;255(5052):1707-10
1553558
J Comp Neurol. 1998 Sep 28;399(3):413-23
9733087
Otol Neurotol. 2006 Dec;27(8):1146-51
16885783
Development. 1999 Apr;126(8):1581-90
10079221
Nat Genet. 1999 Mar;21(3):289-92
10080181
Physiol Rev. 2001 Jul;81(3):1305-52
11427697
Annu Rev Genet. 2009;43:411-37
19694516
Exp Cell Res. 2005 Jun 10;306(2):309-16
15925585
Dev Biol. 2007 Jul 1;307(1):165-78
17531970
Cell Motil Cytoskeleton. 1991;18(3):215-27
1711932
Science. 1988 Jun 24;240(4860):1774-6
3381101
J Assoc Res Otolaryngol. 2009 Sep;10(3):321-40
19373512
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):781-5
18178626
Semin Cell Dev Biol. 1998 Dec;9(6):583-9
9892564
J Neurosci Res. 2008 Nov 1;86(14):3075-85
18543340
Acta Otolaryngol Suppl. 2004 Mar;(551):31-3
15078074
Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16675-80
17895386
Dev Cell. 2009 Jan;16(1):58-69
19154718
Arch Histol Cytol. 2006 Dec;69(4):209-25
17287576
Mol Cell Neurosci. 2007 Jan;34(1):59-68
17113786
Hear Res. 2008 Nov;245(1-2):5-17
18790034
Dev Biol. 2008 Apr 1;316(1):87-99
18291358
Cell Transplant. 2008;17(6):665-78
18819255
Dev Dyn. 2005 Jun;233(2):570-83
15844198
Drug Discov Today. 2005 Oct 1;10(19):1307-12
16214675
Int J Dev Biol. 2007;51(6-7):633-47
17891722
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14206-10
9391178
J Neurosci. 2007 Apr 18;27(16):4313-25
17442815
Curr Opin Otolaryngol Head Neck Surg. 2005 Oct;13(5):294-300
16160524
J Assoc Res Otolaryngol. 2007 Mar;8(1):18-31
17171473
Curr Opin Genet Dev. 2009 Aug;19(4):368-73
19604683
Noise Health. 2003 Jul-Sep;5(20):19-28
14558889
Hear Res. 1987;30(2-3):181-95
3680064
Hear Res. 1984 Aug;15(2):133-42
6490539
Neuroreport. 2005 Sep 28;16(14):1545-9
16148742
Neurosci Lett. 1996 Feb 16;205(1):17-20
8867010
Dev Biol. 2009 Feb 1;326(1):86-100
19013445
Neuron. 1993 Nov;11(5):951-66
8240816
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18396-401
19011097
Hear Res. 1990 Jun;46(1-2):29-40
2380125
J Assoc Res Otolaryngol. 2007 Jun;8(2):194-204
17334849
Acta Otolaryngol. 2001 Jan;121(2):140-2
11349765
J Neurosci. 2009 May 6;29(18):5711-2
19420238
Naturwissenschaften. 1988 Jun;75(6):319-20
3205314
J Comp Neurol. 2006 Dec 10;499(5):691-701
17048225
Hear Res. 2008 Aug;242(1-2):110-6
18585449
Am J Otol. 1994 Jan;15(1):28-34
8109626
Acta Otolaryngol Suppl. 2004 Mar;(551):53-5
15078079
J Neurosci. 2002 Feb 1;22(3):612-3
11826087
J Neurocytol. 1999 Oct-Nov;28(10-11):809-19
10900086
Audiol Neurootol. 2007;12(6):345-58
17664866
Cell Cycle. 2007 Mar 1;6(5):612-9
17351334
Nature. 2008 Sep 25;455(7212):537-41
18754012
Neuroreport. 2007 Dec 3;18(18):1911-4
18007185
Laryngoscope. 2007 Sep;117(9):1629-35
17632425
Adv Otorhinolaryngol. 2009;66:52-63
19494572
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13495-500
14593207
BMC Dev Biol. 2005 Aug 17;5:16
16107213
Arch Otolaryngol Head Neck Surg. 1987 Oct;113(10):1058-62
3620125
J Neurosci. 2007 Feb 7;27(6):1434-44
17287518
Science. 1999 Apr 30;284(5415):770-6
10221902
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7345-50
16648263
Curr Opin Genet Dev. 2006 Oct;16(5):518-24
16919447
J Neurosci. 1990 Aug;10(8):2502-12
2388077
Science. 2000 Feb 25;287(5457):1433-8
10688783
Curr Opin Neurobiol. 2003 Feb;13(1):119-26
12593990
Dev Dyn. 2007 Jan;236(1):156-70
17096404
Am J Otolaryngol. 2009 Jan-Feb;30(1):8-16
19027507
Artif Organs. 2006 Oct;30(10):743-55
17026573
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3152-5
7724532
Mech Dev. 1999 Jun;84(1-2):169-72
10473135
J Neurosci. 1998 Oct 1;18(19):7811-21
9742150
Development. 2000 Aug;127(15):3373-83
10887092
Science. 1995 Feb 3;267(5198):707-11
7839151
Development. 2004 Mar;131(5):965-73
14973298
Hear Res. 1990 Jul;46(3):229-37
2394635
Int J Dev Biol. 2007;51(6-7):463-72
17891709
Exp Cell Res. 2005 Jan 1;302(1):40-7
15541724
Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):8-9
19118205
Am J Pathol. 2007 Jul;171(1):214-26
17591967
Hear Res. 1997 Nov;113(1-2):14-28
9387983
Ann N Y Acad Sci. 2009 Jul;1170:28-33
19686102
Hear Res. 2007 Oct;232(1-2):29-43
17659854
Nature. 2006 Jun 22;441(7096):984-7
16791196
Oncogene. 2001 Dec 20;20(58):8342-57
11840327
Development. 2006 Aug;133(15):2817-26
16790479
Science. 2005 Feb 18;307(5712):1114-8
15653467
J Comp Neurol. 1981 Oct 1;201(4):541-53
7287934
Science. 1993 Mar 12;259(5101):1616-9
8456284
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):21000-5
19064919
Ciba Found Symp. 1991;160:25-39; discussion 40-53
1752167
Acta Otolaryngol Suppl. 2004 Mar;(551):65-8
15078082
Annu Rev Cell Dev Biol. 2009;25:253-75
19575663
Nat Neurosci. 2004 Dec;7(12):1310-8
15543141
Int J Dev Biol. 2007;51(6-7):447-61
17891708
J Assoc Res Otolaryngol. 2000 Sep;1(2):161-71
11545143
J Assoc Res Otolaryngol. 2009 Jun;10(2):173-90
19247714
J Neurosci. 2001 Jul 1;21(13):4712-20
11425898
Exp Neurol. 2001 May;169(1):30-5
11312555
Eur J Neurosci. 2007 Dec;26(11):3016-23
18005071
J Assoc Res Otolaryngol. 2003 Sep;4(3):422-43
14690060
J Clin Invest. 2000 Jun;105(11):1493-9
10841502
Hear Res. 2006 Apr;214(1-2):28-36
16513305
J Comp Neurol. 1993 May 1;331(1):75-96
8320349
Ann Otol Rhinol Laryngol. 1989 Jun;98(6):411-6
2729822
Int J Dev Biol. 2007;51(6-7):649-54
17891723
Curr Opin Otolaryngol Head Neck Surg. 2008 Oct;16(5):465-71
18797290
Hear Res. 1991 Feb;51(2):173-83
1709631
Science. 1993 Mar 12;259(5101):1619-22
8456285
J Neurosci. 2001 Jan 15;21(2):570-80
11160436
Cell Transplant. 2006;15(5):369-80
16970279
Nat Rev Neurosci. 2006 Nov;7(11):837-49
17053809
Int J Dev Biol. 2007;51(6-7):585-95
17891719
Brain Res. 2006 May 26;1091(1):172-85
16626654
Curr Opin Neurobiol. 2008 Aug;18(4):377-82
18929656