title: Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.
abstract: Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice.
authors.affiliation: UCL Ear Institute, London, UK. Electronic address: ruth.r.taylor@ucl.ac.uk.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Taylor
authors.affiliation: UCL Ear Institute, London, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jagger
authors.affiliation: UCL Ear Institute, London, UK; Royal National Throat Nose and Ear Hospital, UCLH NHS Foundation Trust, London, UK.
authors.forename: Shakeel R
authors.initials: SR
authors.lastname: Saeed
authors.affiliation: Addenbrooke's Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Axon
authors.affiliation: Addenbrooke's Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Donnelly
authors.affiliation: Addenbrooke's Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK.
authors.forename: James
authors.initials: J
authors.lastname: Tysome
authors.affiliation: Addenbrooke's Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Moffatt
authors.affiliation: Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Medical Centre, Birmingham, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Irving
authors.affiliation: Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Medical Centre, Birmingham, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Monksfield
authors.affiliation: Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Medical Centre, Birmingham, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Coulson
authors.affiliation: Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester, UK; Salford Royal Infirmary, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Freeman
authors.affiliation: Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester, UK; Salford Royal Infirmary, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Lloyd
authors.affiliation: UCL Ear Institute, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Forge
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D018069:Hair Cells, Vestibular / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009416:Nerve Regeneration; D044968:Regenerative Medicine; D059547:Stereocilia; D014722:Vestibule, Labyrinth / Q000166:cytology* / Q000473:pathology* / Q000502:physiology
keywords: Aging pathologies; Hair cells; Human vestibular; Stereocilia; Supporting cells; Utricle
references.citation: PLoS One. 2012;7(1):e30577
references.pmid: 22299045
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4473-8
references.pmid: 22396594
references.citation: Science. 1993 Mar 12;259(5101):1619-22
references.pmid: 8456285
references.citation: Science. 1993 Mar 12;259(5101):1616-9
references.pmid: 8456284
references.citation: Otol Neurotol. 2007 Feb;28(2):223-31
references.pmid: 17255891
references.citation: Hear Res. 1987;30(2-3):181-95
references.pmid: 3680064
references.citation: J Neurosci. 2014 Nov 26;34(48):15851-60
references.pmid: 25429127
references.citation: Brain Res. 2006 May 26;1091(1):277-81
references.pmid: 16569399
references.citation: Naturwissenschaften. 1988 Jun;75(6):319-20
references.pmid: 3205314
references.citation: J Assoc Res Otolaryngol. 2015 Feb;16(1):67-80
references.pmid: 25261194
references.citation: J Neurocytol. 1999 Oct-Nov;28(10-11):821-35
references.pmid: 10900087
references.citation: Am J Otol. 1983 Jan;4(3):203-13
references.pmid: 6829735
references.citation: Science. 1988 Jun 24;240(4860):1774-6
references.pmid: 3381101
references.citation: Otol Neurotol. 2005 Nov;26(6):1191-5
references.pmid: 16272940
references.citation: Brain Res. 1995 Dec 15;704(1):135-40
references.pmid: 8750975
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2008 Oct;16(5):465-71
references.pmid: 18797290
references.citation: Nature. 2002 Apr 25;416(6883):874-8
references.pmid: 11976689
references.citation: J Comp Neurol. 1995 May 8;355(3):405-17
references.pmid: 7636022
references.citation: Laryngoscope. 2008 May;118(5):821-31
references.pmid: 18300702
references.citation: Acta Otolaryngol Suppl. 1987;444:1-48
references.pmid: 3482777
references.citation: Int J Dev Biol. 2007;51(6-7):597-608
references.pmid: 17891720
references.citation: Science. 1988 Jun 24;240(4860):1772-4
references.pmid: 3381100
references.citation: Hear Res. 1989 Nov;42(2-3):143-56
references.pmid: 2606800
references.citation: Anat Rec (Hoboken). 2012 Nov;295(11):1837-50
references.pmid: 23045231
references.citation: Clin Otolaryngol Allied Sci. 1983 Feb;8(1):53-63
references.pmid: 6131759
references.citation: J Neurosci. 2011 Oct 26;31(43):15329-39
references.pmid: 22031879
references.citation: J Neurosci. 2014 Jan 29;34(5):1998-2011
references.pmid: 24478379
references.citation: J Neurobiol. 2002 Feb 5;50(2):81-92
references.pmid: 11793356
references.citation: Anat Embryol (Berl). 1989;179(5):457-63
references.pmid: 2786353
references.citation: J Neurosci. 2001 Sep 15;21(18):7013-25
references.pmid: 11549711
references.citation: J Neurosci. 2006 Jan 25;26(4):1260-8
references.pmid: 16436613
references.citation: BMJ. 2008 Jan 19;336(7636):124-6
references.pmid: 18202065
references.citation: J Neurosci. 2003 May 15;23(10):4054-65
references.pmid: 12764092
references.citation: Mol Cell Neurosci. 2003 Jun;23(2):169-79
references.pmid: 12812751
references.citation: Hear Res. 1985;19(2):171-82
references.pmid: 4055536
references.citation: Int J Dev Biol. 2007;51(6-7):633-47
references.pmid: 17891722
references.citation: Hear Res. 1991 Feb;51(2):173-83
references.pmid: 1709631
references.citation: Neurosci Lett. 1996 Feb 16;205(1):17-20
references.pmid: 8867010
references.citation: J Comp Neurol. 2013 Apr 15;521(6):1430-48
references.pmid: 23124808
references.citation: J Comp Neurol. 2003 Dec 8;467(2):207-31
references.pmid: 14595769
references.citation: PLoS Genet. 2011 Mar;7(3):e1002032
references.pmid: 21455486
references.citation: Int J Dev Neurosci. 1997 Jul;15(4-5):433-46
references.pmid: 9263024
references.citation: Hear Res. 2013 Mar;297:42-51
references.pmid: 23321648
references.citation: Ann N Y Acad Sci. 2001 Oct;942:210-9
references.pmid: 11710463
references.citation: Hum Mol Genet. 2015 Jan 1;24(1):37-49
references.pmid: 25124451
references.citation: Nature. 1965 Jul 10;207(993):171-4
references.pmid: 5886108
references.citation: Acta Otolaryngol Suppl. 1987;436:103-9
references.pmid: 2823525
references.citation: Neuroscience. 2012 Jul 26;215:209-16
references.pmid: 22546335
references.citation: J Comp Neurol. 1997 Dec 22;389(3):419-43
references.pmid: 9414004
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2005 Dec;13(6):343-8
references.pmid: 16282762
references.citation: Hear Res. 2009 Jan;247(1):17-26
references.pmid: 18809482
references.citation: J Comp Neurol. 1998 Jul 20;397(1):69-88
references.pmid: 9671280
references.citation: Audiol Neurootol. 2002 Sep-Oct;7(5):289-97
references.pmid: 12232498
references.citation: Science. 1999 Jun 11;284(5421):1837-41
references.pmid: 10364557
references.citation: BMJ. 2008 Jan 19;336(7636):130-3
references.pmid: 18089892
references.citation: Am J Otol. 2000 Nov;21(6):847-51
references.pmid: 11078074
references.citation: Cell Tissue Res. 2015 Jun;360(3):633-44
references.pmid: 25381570
references.citation: J Cell Sci. 2013 Apr 1;126(Pt 7):1703-12
references.pmid: 23424196
references.citation: Neuroscience. 2011 Apr 28;180:360-9
references.pmid: 21320575
references.citation: ORL J Otorhinolaryngol Relat Spec. 1980;42(6):336-45
references.pmid: 6109271
references.citation: Hear Res. 2014 Sep;315:49-60
references.pmid: 25016142
references.citation: Hear Res. 1994 Sep;79(1-2):26-38
references.pmid: 7528737
references.citation: Hear Res. 1992 Jan;57(2):166-74
references.pmid: 1733910
references.citation: Otolaryngol Head Neck Surg. 2005 Sep;133(3):323-5
references.pmid: 16143174
references.citation: Adv Otorhinolaryngol. 1973;20:125-41
references.pmid: 4710505
references.citation: J Neurosci. 1999 Mar 15;19(6):2161-70
references.pmid: 10066269
references.citation: Arch Otorhinolaryngol. 1982;236(1):1-6
references.pmid: 6889851
references.citation: Ann N Y Acad Sci. 2001 Oct;942:220-7
references.pmid: 11710464
references.citation: Hear Res. 2000 Jan;139(1-2):97-115
references.pmid: 10601716
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2004 Oct;12(5):439-43
references.pmid: 15377958
references.citation: Science. 1981 Jun 12;212(4500):1286-8
references.pmid: 7233219
references.citation: Annu Rev Physiol. 2011;73:311-34
references.pmid: 21073336
references.citation: Neuroscience. 1997 Aug;79(4):1137-44
references.pmid: 9219972
references.citation: J Microsc. 1987 Jul;147(Pt 1):89-101
references.pmid: 3305958
references.citation: J Comp Neurol. 2008 Nov 20;511(3):396-414
references.pmid: 18803241
references.citation: J Neurosci. 2003 Jun 1;23(11):4395-400
references.pmid: 12805278
references.citation: Nat Neurosci. 2004 Dec;7(12):1310-8
references.pmid: 15543141
references.citation: Clin Otolaryngol Allied Sci. 2004 Apr;29(2):179-82
references.pmid: 15113307
references.citation: J Assoc Res Otolaryngol. 2012 Oct;13(5):609-27
references.pmid: 22752453
references.citation: Drug Discov Today Dis Models. 2013;10(1):null
references.pmid: 24187569
references.citation: J Neurosci. 2002 May 15;22(10):3939-52
references.pmid: 12019313
references.citation: J Laryngol Otol. 1986 Dec;100(12):1367-74
references.pmid: 3492581
references.citation: J Neurosci. 2006 Feb 15;26(7):2115-23
references.pmid: 16481444
references.citation: J Comp Neurol. 2005 Mar 28;484(1):105-20
references.pmid: 15717301
references.citation: Arch Otorhinolaryngol. 1981;230(1):11-9
references.pmid: 7213191