Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2016, Vol. 10 Issue (2) : 143-151     DOI: 10.1007/s11684-016-0451-1
Regeneration of hair cells in the mammalian vestibular system
Wenyan Li1,2,Dan You1,2,Yan Chen1,2,3,Renjie Chai4,5,*(),Huawei Li1,2,6,*()
1. Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China
2. Key Laboratory of Hearing Medicine of the National Health and Family Planning Commission, Shanghai 200031, China
3. Research Center, Affiliated Eye and ENT Hospital, Fudan University, Shanghai 200031, China
4. MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China
5. Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
6. Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Download: PDF(314 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicin-induced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

Keywords utricle      hair cell      regeneration      Atoh1      Notch      Wnt     
Corresponding Authors: Renjie Chai,Huawei Li   
Online First Date: 17 May 2016    Issue Date: 27 May 2016
URL:     OR
Fig.1  Schematic of hair cell regeneration via proliferation and transdifferentiation of recruited Lgr5+ progenitors following hair cell loss in mammalian utricle.
1 Lambert PR. Inner ear hair cell regeneration in a mammal: identification of a triggering factor. Laryngoscope 1994; 104(6 Pt 1): 701–718
pmid: 8196445
2 Fan C, Zou S, Wang J, Zhang B, Song J. Neomycin damage and regeneration of hair cells in both mechanoreceptor and electroreceptor lateral line organs of the larval Siberian sturgeon (Acipenser baerii). J Comp Neurol 2016; 524(7): 1443–1456
doi: 10.1002/cne.23918 pmid: 26502298
3 Sedó-Cabezón L, Jedynak P, Boadas-Vaello P, Llorens J. Transient alteration of the vestibular calyceal junction and synapse in response to chronic ototoxic insult in rats. Dis Model Mech 2015; 8(10): 1323–1337
doi: 10.1242/dmm.021436 pmid: 26398945
4 Slattery EL, Oshima K, Heller S, Warchol ME. Cisplatin exposure damages resident stem cells of the mammalian inner ear. Dev Dyn 2014; 243(10): 1328–1337
doi: 10.1002/dvdy.24150 pmid: 24888499
5 Balak KJ, Corwin JT, Jones JE. Regenerated hair cells can originate from supporting cell progeny: evidence from phototoxicity and laser ablation experiments in the lateral line system. J Neurosci 1990; 10(8): 2502–2512
pmid: 2388077
6 Burns JC, Cox BC, Thiede BR, Zuo J, Corwin JT. In vivo proliferative regeneration of balance hair cells in newborn mice. J Neurosci 2012; 32(19): 6570–6577
doi: 10.1523/JNEUROSCI.6274-11.2012 pmid: 22573679
7 Roberson DF, Weisleder P, Bohrer PS, Rubel EW. Ongoing production of sensory cells in the vestibular epithelium of the chick. Hear Res 1992; 57(2): 166–174
doi: 10.1016/0378-5955(92)90149-H pmid: 1733910
8 Weisleder P, Rubel EW. Hair cell regeneration in the avian vestibular epithelium. Exp Neurol 1992; 115(1): 2–6
doi: 10.1016/0014-4886(92)90211-8 pmid: 1728567
9 Brosel S, Laub C, Averdam A, Bender A, Elstner M. Molecular aging of the mammalian vestibular system. Ageing Res Rev 2016; 26: 72–80
doi: 10.1016/j.arr.2015.12.007 pmid: 26739358
10 Rüsch A, Lysakowski A, Eatock RA. Postnatal development of type I and type II hair cells in the mouse utricle: acquisition of voltage-gated conductances and differentiated morphology. J Neurosci 1998; 18(18): 7487–7501
pmid: 9736667
11 Lopez I, Honrubia V, Lee SC, Schoeman G, Beykirch K. Quantification of the process of hair cell loss and recovery in the chinchilla crista ampullaris after gentamicin treatment. Int J Dev Neurosci 1997; 15(4-5): 447–461
doi: 10.1016/S0736-5748(96)00103-7 pmid: 9263025
12 Forge A, Li L, Corwin JT, Nevill G. Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science 1993; 259(5101): 1616–1619
doi: 10.1126/science.8456284 pmid: 8456284
13 Warchol ME, Lambert PR, Goldstein BJ, Forge A, Corwin JT. Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans. Science 1993; 259(5101): 1619–1622
doi: 10.1126/science.8456285 pmid: 8456285
14 Rubel EW, Dew LA, Roberson DW. Mammalian vestibular hair cell regeneration. Science 1995; 267(5198): 701–707
doi: 10.1126/science.7839150 pmid: 7839150
15 Corwin JT, Warchol ME, Saffer LD, Finley JE, Gu R, Lamber PR. Growth factors as potential drugs for the sensory epithelia of the ear. Ciba Found Symp 1996; 196:167–182, discussion182–187
16 Saffer LD, Gu R, Corwin JT. An RT-PCR analysis of mRNA for growth factor receptors in damaged and control sensory epithelia of rat utricles. Hear Res 1996; 94(1-2): 14–23
doi: 10.1016/0378-5955(95)00228-6 pmid: 8789807
17 Yamashita H, Oesterle EC. Induction of cell proliferation in mammalian inner-ear sensory epithelia by transforming growth factor α and epidermal growth factor. Proc Natl Acad Sci USA 1995; 92(8): 3152–3155
doi: 10.1073/pnas.92.8.3152 pmid: 7724532
18 Kuntz AL, Oesterle EC. Transforming growth factor-α with insulin induces proliferation in rat utricular extrasensory epithelia. Otolaryngol Head Neck Surg 1998; 118(6): 816–824
doi: 10.1016/S0194-5998(98)70275-X pmid: 9627243
19 Zheng JL, Helbig C, Gao WQ. Induction of cell proliferation by fibroblast and insulin-like growth factors in pure rat inner ear epithelial cell cultures. J Neurosci 1997; 17(1): 216–226
pmid: 8987750
20 Kuntz AL, Oesterle EC. Transforming growth factor α with insulin stimulates cell proliferation in vivo in adult rat vestibular sensory epithelium. J Comp Neurol 1998; 399(3): 413–423
doi: 10.1002/(SICI)1096-9861(19980928)399:3<413::AID-CNE9>3.0.CO;2-3 pmid: 9733087
21 Zheng JL, Stewart RR, Gao WQ. Neurotrophin-4/5, brain-derived neurotrophic factor, and neurotrophin-3 promote survival of cultured vestibular ganglion neurons and protect them against neurotoxicity of ototoxins. J Neurobiol 1995; 28(3): 330–340
doi: 10.1002/neu.480280306 pmid: 8568514
22 Kopke RD, Jackson RL, Li G, Rasmussen MD, Hoffer ME, Frenz DA, Costello M, Schultheiss P, Van De Water TR. Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function. Proc Natl Acad Sci USA 2001; 98(10): 5886–5891
doi: 10.1073/pnas.101120898 pmid: 11331776
23 Marchionni MA, Goodearl AD, Chen MS, Bermingham-McDonogh O, Kirk C, Hendricks M, Danehy F, Misumi D, Sudhalter J, Kobayashi K, Wroblewski D, Lynch C, Baldassare M, Hiles Ian, Davis JB, Hsuan JJ, Totty NF, Otsu Masayuki, McBurney RN, Waterfield MD, Stroobant P, Gwynne D. Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature 1993; 362(6418): 312–318
doi: 10.1038/362312a0 pmid: 8096067
24 Gu R, Montcouquiol M, Marchionni M, Corwin JT. Proliferative responses to growth factors decline rapidly during postnatal maturation of mammalian hair cell epithelia. Eur J Neurosci 2007; 25(5): 1363–1372
doi: 10.1111/j.1460-9568.2007.05414.x pmid: 17425563
25 Montcouquiol M, Corwin JT. Intracellular signals that control cell proliferation in mammalian balance epithelia: key roles for phosphatidylinositol-3 kinase, mammalian target of rapamycin, and S6 kinases in preference to calcium, protein kinase C, and mitogen-activated protein kinase. J Neurosci 2001; 21(2): 570–580
pmid: 11160436
26 Navaratnam DS, Su HS, Scott SP, Oberholtzer JC. Proliferation in the auditory receptor epithelium mediated by a cyclic AMP-dependent signaling pathway. Nat Med 1996; 2(10): 1136–1139
doi: 10.1038/nm1096-1136 pmid: 8837614
27 Montcouquiol M, Corwin JT. Brief treatments with forskolin enhance s-phase entry in balance epithelia from the ears of rats. J Neurosci 2001; 21(3): 974–982
pmid: 11157083
28 Burns JC, On D, Baker W, Collado MS, Corwin JT. Over half the hair cells in the mouse utricle first appear after birth, with significant numbers originating from early postnatal mitotic production in peripheral and striolar growth zones. J Assoc Res Otolaryngol 2012; 13(5): 609–627
doi: 10.1007/s10162-012-0337-0 pmid: 22752453
29 Davies D, Magnus C, Corwin JT. Developmental changes in cell-extracellular matrix interactions limit proliferation in the mammalian inner ear. Eur J Neurosci 2007; 25(4): 985–998
doi: 10.1111/j.1460-9568.2007.05355.x pmid: 17331195
30 Meyers JR, Corwin JT. Shape change controls supporting cell proliferation in lesioned mammalian balance epithelium. J Neurosci 2007; 27(16): 4313–4325
doi: 10.1523/JNEUROSCI.5023-06.2007 pmid: 17442815
31 Burns JC, Christophel JJ, Collado MS, Magnus C, Carfrae M, Corwin JT. Reinforcement of cell junctions correlates with the absence of hair cell regeneration in mammals and its occurrence in birds. J Comp Neurol 2008; 511(3): 396–414
doi: 10.1002/cne.21849 pmid: 18803241
32 Burns JC, Collado MS, Oliver ER, Corwin JT. Specializations of intercellular junctions are associated with the presence and absence of hair cell regeneration in ears from six vertebrate classes. J Comp Neurol 2013; 521(6): 1430–1448
doi: 10.1002/cne.23250 pmid: 23124808
33 Burns JC, Corwin JT. Responses to cell loss become restricted as the supporting cells in mammalian vestibular organs grow thick junctional actin bands that develop high stability. J Neurosci 2014; 34(5): 1998–2011
doi: 10.1523/JNEUROSCI.4355-13.2014 pmid: 24478379
34 Whitlon DS. E-cadherin in the mature and developing organ of Corti of the mouse. J Neurocytol 1993; 22(12): 1030–1038
doi: 10.1007/BF01235747 pmid: 8106878
35 Hackett L, Davies D, Helyer R, Kennedy H, Kros C, Lawlor P, Rivolta MN, Holley M. E-cadherin and the differentiation of mammalian vestibular hair cells. Exp Cell Res 2002; 278(1): 19–30
doi: 10.1006/excr.2002.5574 pmid: 12126954
36 Lu Z, Corwin JT. The influence of glycogen synthase kinase 3 in limiting cell addition in the mammalian ear. Dev Neurobiol 2008; 68(8): 1059–1075
doi: 10.1002/dneu.20635 pmid: 18470861
37 Collado MS, Thiede BR, Baker W, Askew C, Igbani LM, Corwin JT. The postnatal accumulation of junctional E-cadherin is inversely correlated with the capacity for supporting cells to convert directly into sensory hair cells in mammalian balance organs. J Neurosci 2011; 31(33): 11855–11866
doi: 10.1523/JNEUROSCI.2525-11.2011 pmid: 21849546
38 Kawamoto K, Izumikawa M, Beyer LA, Atkin GM, Raphael Y. Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity. Hear Res 2009; 247(1): 17–26
doi: 10.1016/j.heares.2008.08.010 pmid: 18809482
39 Collado MS, Burns JC, Meyers JR, Corwin JT. Variations in shape-sensitive restriction points mirror differences in the regeneration capacities of avian and mammalian ears. PLoS ONE 2011; 6(8): e23861
doi: 10.1371/journal.pone.0023861 pmid: 21909368
40 Li H, Liu H, Heller S. Pluripotent stem cells from the adult mouse inner ear. Nat Med 2003; 9(10): 1293–1299
doi: 10.1038/nm925 pmid: 12949502
41 Chai R, Xia A, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, Cheng AG. Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. J Assoc Res Otolaryngol 2011; 12(4): 455–469
doi: 10.1007/s10162-011-0267-2 pmid: 21472479
42 Chai R, Kuo B, Wang T, Liaw EJ, Xia A, Jan TA, Liu Z, Taketo MM, Oghalai JS, Nusse R, Zuo J, Cheng AG. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci USA 2012; 109(21): 8167–8172
doi: 10.1073/pnas.1202774109 pmid: 22562792
43 Shi F, Hu L, Edge ASB. Generation of hair cells in neonatal mice by b-catenin overexpression in Lgr5-positive cochlear progenitors. Proc Natl Acad Sci USA 2013; 110(34): 13851–13856
doi: 10.1073/pnas.1219952110 pmid: 23918377
44 Bramhall NF, Shi F, Arnold K, Hochedlinger K, Edge ASB. Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea. Stem Cell Rep 2014; 2(3): 311–322
doi: 10.1016/j.stemcr.2014.01.008 pmid: 24672754
45 Li W, Wu J, Yang J, Sun S, Chai R, Chen ZY, Li H. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci USA 2015; 112(1): 166–171
doi: 10.1073/pnas.1415901112 pmid: 25535395
46 Wang T, Chai R, Kim GS, Pham N, Jansson L, Nguyen DH, Kuo B, May LA, Zuo J, Cunningham LL, Cheng AG. Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Nat Commun 2015; 6: 6613
doi: 10.1038/ncomms7613 pmid: 25849379
47 Lin J, Zhang X, Wu F, Lin W. Hair cell damage recruited Lgr5-expressing cells are hair cell progenitors in neonatal mouse utricle. Front Cell Neurosci 2015; 9: 113
doi: 10.3389/fncel.2015.00113 pmid: 25883551
48 Forge A, Li L, Nevill G. Hair cell recovery in the vestibular sensory epithelia of mature guinea pigs. J Comp Neurol 1998; 397(1): 69–88
doi: 10.1002/(SICI)1096-9861(19980720)397:1<69::AID-CNE6>3.0.CO;2-G pmid: 9671280
49 Golub JS, Tong L, Ngyuen TB, Hume CR, Palmiter RD, Rubel EW, Stone JS. Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin. J Neurosci 2012; 32(43): 15093–15105
doi: 10.1523/JNEUROSCI.1709-12.2012 pmid: 23100430
50 Bermingham NA, Hassan BA, Price SD, Vollrath MA, Ben-Arie N, Eatock RA, Bellen HJ, Lysakowski A, Zoghbi HY. Math1: an essential gene for the generation of inner ear hair cells. Science 1999; 284(5421): 1837–1841
doi: 10.1126/science.284.5421.1837 pmid: 10364557
51 Zheng JL, Gao WQ. Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears. Nat Neurosci 2000; 3(6): 580–586
doi: 10.1038/75753 pmid: 10816314
52 Shou J, Zheng JL, Gao WQ. Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1. Mol Cell Neurosci 2003; 23(2): 169–179
doi: 10.1016/S1044-7431(03)00066-6 pmid: 12812751
53 Staecker H, Praetorius M, Baker K, Brough DE. Vestibular hair cell regeneration and restoration of balance function induced by math1 gene transfer. Otol Neurotol 2007; 28(2): 223–231
doi: 10.1097/MAO.0b013e31802b3225 pmid: 17255891
54 Staecker H, Schlecker C, Kraft S, Praetorius M, Hsu C, Brough DE. Optimizing atoh1-induced vestibular hair cell regeneration. Laryngoscope 2014; 124(Suppl 5): S1–S12
doi: 10.1002/lary.24775 pmid: 24938696
55 Schlecker C, Praetorius M, Brough DE, Presler RG Jr, Hsu C, Plinkert PK, Staecker H. Selective atonal gene delivery improves balance function in a mouse model of vestibular disease. Gene Ther 2011; 18(9): 884–890
doi: 10.1038/gt.2011.33 pmid: 21472006
56 Xu JC, Huang DL, Hou ZH, Guo WW, Sun JH, Zhao LD, Yu N, Young WY, He DZ, Yang SM. Type I hair cell regeneration induced by Math1 gene transfer following neomycin ototoxicity in rat vestibular sensory epithelium. Acta Otolaryngol 2012; 132(8): 819–828
pmid: 22668196
57 Gao Z, Kelly MC, Yu D, Wu H, Lin X, Chi FL, Chen P. Spatial and age-dependent hair cell generation in the postnatal mammalian utricle. Mol Neurobiol 2016; 53(3): 1601–1612
pmid: 25666161
58 Slowik AD, Bermingham-McDonogh O. Hair cell generation by notch inhibition in the adult mammalian cristae. J Assoc Res Otolaryngol 2013; 14(6): 813–828
doi: 10.1007/s10162-013-0414-z pmid: 23989618
59 Lanford PJ, Lan Y, Jiang R, Lindsell C, Weinmaster G, Gridley T, Kelley MW. Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat Genet 1999; 21(3): 289–292
doi: 10.1038/6804 pmid: 10080181
60 Wang GP, Chatterjee I, Batts SA, Wong HT, Gong TW, Gong SS, Raphael Y. Notch signaling and Atoh1 expression during hair cell regeneration in the mouse utricle. Hear Res 2010; 267(1-2): 61–70
doi: 10.1016/j.heares.2010.03.085 pmid: 20433915
61 Mizutari K, Fujioka M, Hosoya M, Bramhall N, Okano HJ, Okano H, Edge AS. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron 2013; 77(1): 58–69
doi: 10.1016/j.neuron.2012.10.032 pmid: 23312516
62 Lin V, Golub JS, Nguyen TB, Hume CR, Oesterle EC, Stone JS. Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles. J Neurosci 2011; 31(43): 15329–15339
doi: 10.1523/JNEUROSCI.2057-11.2011 pmid: 22031879
63 Jung JY, Avenarius MR, Adamsky S, Alpert E, Feinstein E, Raphael Y. siRNA targeting Hes5 augments hair cell regeneration in aminoglycoside-damaged mouse utricle. Mol Ther 2013; 21(4): 834–841
doi: 10.1038/mt.2013.18 pmid: 23439501
64 Brigande JV, Heller S. Quo vadis, hair cell regeneration? Nat Neurosci 2009; 12(6): 679–685
doi: 10.1038/nn.2311 pmid: 19471265
65 Chen P, Segil N. p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development 1999; 126(8): 1581–1590
pmid: 10079221
66 Löwenheim H, Furness DN, Kil J, Zinn C, Gültig K, Fero ML, Frost D, Gummer AW, Roberts JM, Rubel EW, Hackney CM, Zenner HP. Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti. Proc Natl Acad Sci USA 1999; 96(7): 4084–4088
doi: 10.1073/pnas.96.7.4084 pmid: 10097167
67 White PM, Doetzlhofer A, Lee YS, Groves AK, Segil N. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 2006; 441(7096): 984–987
doi: 10.1038/nature04849 pmid: 16791196
68 Sage C, Huang M, Karimi K, Gutierrez G, Vollrath MA, Zhang DS, García-Añoveros J, Hinds PW, Corwin JT, Corey DP, Chen ZY. Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein. Science 2005; 307(5712): 1114–1118
doi: 10.1126/science.1106642 pmid: 15653467
69 Sage C, Huang M, Vollrath MA, Brown MC, Hinds PW, Corey DP, Vetter DE, Chen ZY. Essential role of retinoblastoma protein in mammalian hair cell development and hearing. Proc Natl Acad Sci USA 2006; 103(19): 7345–7350
doi: 10.1073/pnas.0510631103 pmid: 16648263
70 Weber T, Corbett MK, Chow LM, Valentine MB, Baker SJ, Zuo J. Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells. Proc Natl Acad Sci USA 2008; 105(2): 781–785
doi: 10.1073/pnas.0708061105 pmid: 18178626
71 Yu Y, Weber T, Yamashita T, Liu Z, Valentine MB, Cox BC, Zuo J. In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice. J Neurosci 2010; 30(17): 5927–5936
doi: 10.1523/JNEUROSCI.5989-09.2010 pmid: 20427652
72 Laine H, Sulg M, Kirjavainen A, Pirvola U. Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev Biol 2010; 337(1): 134–146
doi: 10.1016/j.ydbio.2009.10.027 pmid: 19854167
73 Loponen H, Ylikoski J, Albrecht JH, Pirvola U. Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression. PLoS ONE 2011; 6(11): e27360–e12
doi: 10.1371/journal.pone.0027360 pmid: 22073316
74 Burns JC, Yoo JJ, Atala A, Jackson JD. MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic supporting cells in vitro. PLoS ONE 2012; 7(10): e48704
doi: 10.1371/journal.pone.0048704 pmid: 23119091
75 Waqas M, Guo L, Zhang S, Chen Y. Zhang X, Wang L, Tang M, Shi H, Bird P I, Li H, Chai R. Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea. Oncotorget<Date> 2016 Apr 7.</Date> [Epub ahead of print] doi: 10.18632/oncotarget.8636
doi: 10.18632/oncotarget.8636 pmid: 27070092
[1] Yanfei Wang,Yueyue Liu,Hongyun Nie,Xin Ma,Zhigang Xu. Alternative splicing of inner-ear-expressed genes[J]. Front. Med., 2016, 10(3): 250-257.
[2] Muhammad Waqas,Shasha Zhang,Zuhong He,Mingliang Tang,Renjie Chai. Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea[J]. Front. Med., 2016, 10(3): 237-249.
[3] Aining Xu,Lin Cheng. Chemical transdifferentiation: closer to regenerative medicine[J]. Front. Med., 2016, 10(2): 152-165.
[4] Samuel Chege Gitau,Xuelian Li,Dandan Zhao,Zhenfeng Guo,Haihai Liang,Ming Qian,Lifang Lv,Tianshi Li,Bozhi Xu,Zhiguo Wang,Yong Zhang,Chaoqian Xu,Yanjie Lu,Zhiming Du,Hongli Shan,Baofeng Yang. Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling[J]. Front. Med., 2015, 9(4): 444-456.
[5] Siming Yang, Sha Huang, Changjiang Feng, Xiaobing Fu. Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration[J]. Front Med, 2012, 6(1): 41-47.
[6] Zhiyuan Zhang. Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region[J]. Front Med, 2011, 5(4): 401-413.
[7] ZHANG Xufeng, YU Liang, LU Yi. Wnt/β-catenin signaling pathway and its role in hepatocellular carcinoma[J]. Front. Med., 2008, 2(3): 216-228.
[8] GE Jian, LIU Jingbo. The stem cell and tissue engineering research in Chinese ophthalmology[J]. Front. Med., 2007, 1(1): 6-10.
Full text