본문 바로가기
KERD
논문KCI 등재

와우 줄기세포 연구의 과거와 현재

The Past and Present of the Research on Cochlear Stem Cell

이동희
대한이비인후과학회 (Korean Society of Otorhinolaryngology-Head and Neck Surgery)|2011.04|대한이비인후과학회지 두경부외과학 (Korean Journal of Otorhinolaryngology-Head and Neck Surgery)|제54권 제4호|pp. 247-256

1

조회

0

다운로드

2

인용

0

참고문헌

주제분류이비인후과학

초록

Hearing loss is the most frequent sensory deficit in the human population and can occur at any age. Hearing loss ranges from mild to profound, can be conductive, sensorineural or mixed type and may be congenital or acquired. Sometimes, some of hearing loss can be cured by medical or surgical interventions but most of hearing loss is irreversible and many patients struggle in their daily activities and their quality of life suffers. Although hearing aids as well as cochlear implants can give good solution to patients with a hearing loss that cannot be cured, both of them have some limitations and cannot solve the hearing problem perfectly. Recent scientific achievements in cochlear stem cell research and regenerative medicine can suggest ultimate solution to researchers as well as doctors and can give a hope to patients with a hearing loss and their family. Until now, mammalian cochlear hair cells have been known to be never replaced or regenerated, such that insults to the cochlea cause progressive and permanent hearing loss of variable degree. However, non-mammalian vertebrates are capable of replacing lost hair cells and have stem cells in their cochlea, which has recently led to efforts to understand the molecular and cellular basis of regenerative responses in different vertebrate species. In this article, I review the development of mammalian cochlea, focusing on the molecular events related with the development and regeneration. I also introduce the progress in overcoming the limits to mammalian cochlear hair cell regeneration and recent efforts to cochlear regenerative medicine.

Abstract

Hearing loss is the most frequent sensory deficit in the human population and can occur at any age. Hearing loss ranges from mild to profound, can be conductive, sensorineural or mixed type and may be congenital or acquired. Sometimes, some of hearing loss can be cured by medical or surgical interventions but most of hearing loss is irreversible and many patients struggle in their daily activities and their quality of life suffers. Although hearing aids as well as cochlear implants can give good solution to patients with a hearing loss that cannot be cured, both of them have some limitations and cannot solve the hearing problem perfectly. Recent scientific achievements in cochlear stem cell research and regenerative medicine can suggest ultimate solution to researchers as well as doctors and can give a hope to patients with a hearing loss and their family. Until now, mammalian cochlear hair cells have been known to be never replaced or regenerated, such that insults to the cochlea cause progressive and permanent hearing loss of variable degree. However, non-mammalian vertebrates are capable of replacing lost hair cells and have stem cells in their cochlea, which has recently led to efforts to understand the molecular and cellular basis of regenerative responses in different vertebrate species. In this article, I review the development of mammalian cochlea, focusing on the molecular events related with the development and regeneration. I also introduce the progress in overcoming the limits to mammalian cochlear hair cell regeneration and recent efforts to cochlear regenerative medicine.

참고문헌 (68)

  1. Groves AK, "The challenge of hair cell regeneration", Exp Biol Med(Maywood), 235(4), pp.434~446 (2010)
  2. Merchant SN, "Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss", Otol Neurotol, 26(2), pp.151~160 (2005)
  3. Nadol JB Jr, "Histopathology and molecular genetics of hearing loss in the human", Int J Pediatr Otorhinolaryngol, 61(1), pp.1~15 (2001)
  4. Bhatt KA, "Morphometric analysis of age-related changes in the human basilar membrane", Ann Otol Rhinol Laryngol, 110(12), pp.1147~1153 (2001)
  5. Barald KF, "From placode to polarization:new tunes in inner ear development", Development, 131(17), pp.4119~4130 (2004)
  6. Ladher RK, "FGF8 initiates inner ear induction in chick and mouse", Genes Dev, 19(5), pp.603~613 (2005)
  7. Fritzsch B, "The molecular basis of neurosensory cell formation in ear development:a blueprint for hair cell and sensory neuron regeneration", Bioessays, 28(12), pp.1181~1193 (2006)
  8. Fritzsch B, "Cells,molecules and morphogenesis:the making of the vertebrate ear", Brain Res, 1091(1), pp.151~171 (2006)
  9. Puligilla C, "Building the world’s best hearing aid; regulation of cell fate in the cochlea", Curr Opin Genet Dev, 19(4), pp.368~373 (2009)
  10. Driver EC, "Specification of cell fate in the mammalian cochlea", Birth Defects Res C Embryo Today, 87(3), pp.212~221 (2009)
  11. Kelley MW, "Regulation of cell fate and patterning in the developing mammalian cochlea", Curr Opin Otolaryngol Head Neck Surg, 17(5), pp.381~387 (2009)
  12. Savary E, "Distinct population of hair cell progenitors can be isolated from the postnatal mouse cochlea using side population analysis", Stem Cells, 25(2), pp.332~339 (2007)
  13. Zhai S, "Isolation and culture of hair cell progenitors from postnatal rat cochleae", J Neurobiol, 65(3), pp.282~293 (2005)
  14. White PM, "Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells", Nature, 441(7096), pp.984~987 (2006)
  15. Izumikawa M, "Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals", Nat Med, 11(3), pp.271~276 (2005)
  16. Bermingham-McDonogh O, "Hair cell regeneration:winging our way towards a sound future", Curr Opin Neurobiol, 13(1), pp.119~126 (2003)
  17. Yamamoto N, "Inhibition of Notch", RBP-J signaling induces hair cell formation in neonate mouse cochleas, 2006, pp.84(1), 37~45
  18. Takebayashi S, "Multiple roles of Notch signaling in cochlear development", Dev Biol, 307(1), pp.165~178 (2007)
  19. Zine A,, "Notch signaling regulates the pattern of auditory hair cell differentiation in mammals", Development, 127(15), pp.3373~3383 (2000)
  20. Hori R, "Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea", Neuroreport, 18(18), pp.1911~1914 (2007)
  21. Chen P, "p27(Kip1)links cell proliferation to morphogenesis in the developing organ of Corti", Development, 126(8), pp.1581~1590 (1999)
  22. Corwin JT, "Regeneration in the auditory system", Exp Neurol, 115(1), pp.7~12 (1992)
  23. Ryals BM, "Hair cell regeneration after acoustic trauma in adult Coturnix quail", Science, 240(4860), pp.1774~1776 (1988)
  24. Cotanche DA, "Regeneration of hair cell stereociliary bundles in the chick cochlea following severe acoustic trauma", Hear Res, 30(2), pp.181~195 (1987)
  25. Cruz RM, "Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea", Arch Otolaryngol Head Neck Surg, 113(10), pp.1058~1062 (1987)
  26. Smolders JW, "Functional recovery in the avian ear after hair cell regeneration", Audiol Neurootol, 4(6), pp.286~302 (1999)
  27. Corwin JT, "Hair cell regeneration: the identities of progenitor cells, potential triggers and instructive cues", Ciba Found Symp, 160, pp.103~120 (1991)
  28. Stone JS, "Hair cell regeneration in the avian auditory epithelium", Int J Dev Biol, 51(6), pp.633~647 (2007)
  29. Roberson DW, "Light microscopic evidence that direct transdifferentiation gives rise to new hair cells in regenerating avian auditory epithelium", Aud Neurosci, 2, pp.11~ (1996)
  30. Vater M, "Hearing organ evolution and specialization: early and later mammals", pp.256~ (2004), Springer-Verlag
  31. Warchol ME, "Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans", Science, 259(5101), pp.1619~1622 (1993)
  32. Forge A, "Ultrastructural evidence for hair cell regeneration in the mammalian inner ear", Science, 259(5101), pp.1616~1619 (1993)
  33. Hawkins JE Jr, "Hearing loss and cochlear pathology in monkeys after noise exposure", Acta Otolaryngol, 81(3), pp.337~343 (1976)
  34. Raphael Y, "Reorganization of cytoskeletal and junctional proteins during cochlear hair cell degeneration", Cell Motil Cytoskeleton, 18(3), pp.215~227 (1991)
  35. Oshima K, "Differential distribution of stem cells in the auditory and vestibular organs of the inner ear", J Assoc Res Otolaryngol, 8(1), pp.18~31 (2007)
  36. Oshima K, "Mechanosensitive hair cell-like cells from embryonic and induced pluripotent stem cells", Cell, 141(4), pp.704~716 (2010)
  37. Boyer LA, "Core transcriptional regulatory circuitry in human embryonic stem cells", Cell, 122(6), pp.947~956 (2005)
  38. Kelley MW, "Regulation of cell fate in the sensory epithelia of the inner ear", Nat Rev Neurosci, 7(11), pp.837~849 (2006)
  39. Kelley MW, "Cellular commitment and differentiation in the organ of Corti", Int J Dev Biol, 51(6), pp.571~583 (2007)
  40. Ryan AF, "The cell cycle and the development and regeneration of hair cells", Curr Top Dev Biol, 57, pp.449~466 (2003)
  41. Bermingham NA, "Math1:an essential gene for the generation of inner ear hair cells", Science, 284(5421), pp.1837~1841 (1999)
  42. Chen P, "The role of Math1 in inner ear development:Uncoupling the establishment of the sensory primordium from hair cell fate determination", Development, 129(10), pp.2495~2505 (2002)
  43. Kawamoto K, "Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo", J Neurosci, 23(11), pp.4395~4400 (2003)
  44. Zheng JL, "Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears", Nat Neurosci, 3(6), pp.580~586 (2000)
  45. Gubbels SP, "Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer", Nature, 455(7212), pp.537~541 (2008)
  46. Baker K, "Repair of the vestibular system via adenovector delivery of Atoh1:a potential treatment for balance disorders", Adv Otorhinolaryngol, 66, pp.52~63 (2009)
  47. Staecker H, "Vestibular hair cell regeneration and restoration of balance function induced by math1 gene transfer", Otol Neurotol, 28(2), pp.223~231 (2007)
  48. Lewis J, "Notch signalling and the control of cell fate choices in vertebrates", Semin Cell Dev Biol, 9(6), pp.583~589 (1998)
  49. Lewis J, "Rules for the production of sensory cells", Ciba Found Symp, 160, pp.25~39 (1991)
  50. Lanford PJ, "Notch signalling pathway mediates hair cell development in mammalian cochlea", Nat Genet, 21(3), pp.289~292 (1999)
  51. Lewis AK, "Distinct expression patterns of notch family receptors and ligands during development of the mammalian inner ear", Mech Dev, 78(1), pp.159~163 (1998)
  52. Morrison A, "Expression of Delta1 and Serrate1 (Jagged1) in the mouse inner ea", Mech Dev, 84(1), pp.169~172 (1999)
  53. Shailam R, "Expression of proneural and neurogenic genes in the embryonic mammalian vestibular system", J Neurocytol, 28(10), pp.809~819 (1999)
  54. Doetzlhofer A, "Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti", Dev Cell, 16(1), pp.58~69 (2009)
  55. Hayashi T, "Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea", Dev Biol, 316, pp.87~99 (2008)
  56. Lanford PJ, "Expression of Math1 and HES5 in the cochleae of wildtype and Jag2 mutant mice", J Assoc Res Otolaryngol, 1(2), pp.161~171 (2000)
  57. Zheng JL, "Hes1 is a negative regulator of inner ear hair cell differentiation", Development, 127(21), pp.4551~4560 (2000)
  58. Zine A, "Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear", J Neurosci, 21, pp.4712~4720 (2001)
  59. Brooker R, "Notch ligands with contrasting functions:Jagged1 and Delta1 in the mouse inner ear", Development, 133(7), pp.1277~1286 (2006)
  60. Kiernan AE, "The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear", Development, 132(19), pp.4353~4362 (2005)
  61. Oshima K, "Curing hearing loss:Patient expectations,health care practitioners,and basic science", J Commun Disord, 43(4), pp.311~318 (2010)
  62. Stone JS, "Delta1 expression during avian hair cell regeneration", Development, 126(5), pp.961~973 (1999)
  63. Takahashi K, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell, 126(4), pp.663~676 (2006)
  64. Freter S, "Progressive restriction of otic fate:the role of FGF and Wnt in resolving inner ear potential", Development, 135(20), pp.3415~3424 (2008)
  65. Phillips BT, "A direct role for Fgf but not Wnt in otic placode induction", Development, 131(4), pp.923~931 (2004)
  66. Pirvola U, "FGF", FGFR-2(IIIb)signaling is essential for inner ear morphogenesis, 2000, pp.20(16), 6125~34
  67. Pirvola U, "FGFR1 is required for the development of the auditory sensory epithelium", Neuron, 35(4), pp.671~680 (2002)
  68. Li H, "Generation of hair cells by stepwise differentiation of embryonic stem cells", Proc Natl Acad Sci U S A, 100(23), pp.13495~500 (2003)

관련 논문AI추천

Stem Cell Therapy for Sensorineural Hearing Loss, Still Alive?박용호대한청각학회 · Journal of Audiology & Otology2015 · 제19권 제2호귀에 존재하는 내인성 성체줄기세포박경호대한이비인후과학회 · 대한이비인후과학회지 두경부외과학2013 · 제56권 제12호Hair Cell Regeneration: From Animals to HumansAlan G. Cheng, Julia M. Abitbol, Sung-Won Choi대한이비인후과학회 · Clinical and Experimental Otorhinolaryngology2024 · 제17권 제1호청각 오가노이드 연구 어디까지 진행되었나?이민영대한이비인후과학회 · 대한이비인후과학회지 두경부외과학2025 · 제68권 제8호전정기관과 와우의 발생황찬호대한이비인후과학회 · 대한이비인후과학회지 두경부외과학2010 · 제53권 제5호내이 유전자 치료의 발전과 기질로서의 지지세포의 중요성김영호대한이비인후과학회 · 대한이비인후과학회지 두경부외과학2007 · 제50권 제12호

이 간행물의 다른 논문 (3건)

두경부에 발생한 신경초종에 대한 임상적 고찰황병언, 이경석, 양윤수, 박희택, 임상호, 홍기환pp. 278-282충수돌기에 전이된 원발성 이하선 악성 흑색종 1예정기홍, 이준규, 김종승, 김재영pp. 283-287하악하 도서형 피판을 이용한 하구순 재건술김준식, 김호엽, 우승훈, 김진평pp. 293-296
원문 보기