Anatomy and Cellular Constituents of the Human Olfactory Mucosa: A Review

 

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Abstract

Studies using animal models have recently suggested that the olfactory mucosa may be a source of cells capable of stimulating and contributing to complex neurologic regeneration. Several groups have already transplanted cell derivatives from the olfactory mucosa into injury models, and the results so far have been promising. To fully appreciate the meaning of these experiments, a better understanding of the cellular biology and physiology of the olfactory system is necessary. It is therefore of utmost importance for us to first identify and understand its constituents.

• References

• 1 Nordin S, Brämerson A. Complaints of olfactory disorders: epidemiology, assessment and clinical implications. Curr Opin Allergy Clin Immunol 2008; 8 (1) 10-15
  CrossrefPubMedGoogle Scholar
• 2 Keyvan-Fouladi N, Raisman G, Li Y. Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing cells in adult rats. J Neurosci 2003; 23 (28) 9428-9434
  PubMedGoogle Scholar
• 3 Raisman G. Olfactory ensheathing cells—another miracle cure for spinal cord injury?. Nat Rev Neurosci 2001; 2 (5) 369-375
  CrossrefPubMedGoogle Scholar
• 4 Mackay-Sim A, Féron F, Cochrane J , et al. Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain 2008; 131 (Pt 9) 2376-2386
  CrossrefPubMedGoogle Scholar
• 5 Seiden AM. Taste and Smell Disorders. New York, NY: Thieme; 1997
  Google Scholar
• 6 Féron F, Perry C, McGrath JJ, Mackay-Sim A. New techniques for biopsy and culture of human olfactory epithelial neurons. Arch Otolaryngol Head Neck Surg 1998; 124 (8) 861-866
  CrossrefPubMedGoogle Scholar
• 7 Leopold DA, Hummel T, Schwob JE, Hong SC, Knecht M, Kobal G. Anterior distribution of human olfactory epithelium. Laryngoscope 2000; 110 (3 Pt 1) 417-421
  CrossrefPubMedGoogle Scholar
• 8 Paik SI, Lehman MN, Seiden AM, Duncan HJ, Smith DV. Human olfactory biopsy. The influence of age and receptor distribution. Arch Otolaryngol Head Neck Surg 1992; 118 (7) 731-738
  CrossrefPubMedGoogle Scholar
• 9 Watelet JB, Strolin-Benedetti M, Whomsley R. Defence mechanisms of olfactory neuro-epithelium: mucosa regeneration, metabolising enzymes and transporters. B-ENT 2009; 5 (Suppl 13): 21-37
  PubMedGoogle Scholar
• 10 Holbrook EH, Leopold DA, Schwob JE. Abnormalities of axon growth in human olfactory mucosa. Laryngoscope 2005; 115 (12) 2144-2154
  CrossrefPubMedGoogle Scholar
• 11 Cuschieri A, Bannister LH. The development of the olfactory mucosa in the mouse: light microscopy. J Anat 1975; 119 (Pt 2) 277-286
  PubMedGoogle Scholar
• 12 Cuschieri A, Bannister LH. The development of the olfactory mucosa in the mouse: electron microscopy. J Anat 1975; 119 (Pt 3) 471-498
  PubMedGoogle Scholar
• 13 Getchell TV, Bartoshuk LM, Doty RL, Snow JB. Smell and Taste in Health and Disease. New York, NY: Raven Press; 1991
  Google Scholar
• 14 Farbman AI, Squinto LM. Early development of olfactory receptor cell axons. Brain Res 1985; 351 (2) 205-213
  PubMedGoogle Scholar
• 15 Marin-Padilla M, Amieva MR. Early neurogenesis of the mouse olfactory nerve: Golgi and electron microscopic studies. J Comp Neurol 1989; 288 (2) 339-352
  CrossrefPubMedGoogle Scholar
• 16 Valverde F, Santacana M, Heredia M. Formation of an olfactory glomerulus: morphological aspects of development and organization. Neuroscience 1992; 49 (2) 255-275
  CrossrefPubMedGoogle Scholar
• 17 Bossy J. Development of olfactory and related structures in staged human embryos. Anat Embryol (Berl) 1980; 161 (2) 225-236
  CrossrefPubMedGoogle Scholar
• 18 Pyatkina GA. Development of the olfactory epithelium in man. Z Mikrosk Anat Forsch 1982; 96 (2) 361-372
  PubMedGoogle Scholar
• 19 Johnson EW, Eller PM, Jafek BW. Distribution of OMP-, PGP 9.5- and CaBP-like immunoreactive chemoreceptor neurons in the developing human olfactory epithelium. Anat Embryol (Berl) 1995; 191 (4) 311-317
  CrossrefPubMedGoogle Scholar
• 20 Chuah MI, Zheng DR. The human primary olfactory pathway: fine structural and cytochemical aspects during development and in adults. Microsc Res Tech 1992; 23 (1) 76-85
  CrossrefPubMedGoogle Scholar
• 21 Sarnat HB. Olfactory reflexes in the newborn infant. J Pediatr 1978; 92 (4) 624-626
  CrossrefPubMedGoogle Scholar
• 22 Winberg J, Porter RH. Olfaction and human neonatal behaviour: clinical implications. Acta Paediatr 1998; 87 (1) 6-10
  CrossrefPubMedGoogle Scholar
• 23 Farbman AI, Margolis FL. Olfactory marker protein during ontogeny: immunohistochemical localization. Dev Biol 1980; 74 (1) 205-215
  CrossrefPubMedGoogle Scholar
• 24 Weiler E, Benali A. Olfactory epithelia differentially express neuronal markers. J Neurocytol 2005; 34 (3–5) 217-240
  CrossrefPubMedGoogle Scholar
• 25 Kimura M, Umehara T, Udagawa J, Kawauchi H, Otani H. Development of olfactory epithelium in the human fetus: scanning electron microscopic observations. Congenit Anom (Kyoto) 2009; 49 (3) 102-107
  CrossrefPubMedGoogle Scholar
• 26 Gu J, Su T, Chen Y, Zhang QY, Ding X. Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity. Toxicol Appl Pharmacol 2000; 165 (2) 158-162
  CrossrefPubMedGoogle Scholar
• 27 Heydel J-M, Holsztynska EJ, Legendre A, Thiebaud N, Artur Y, Le Bon A-M. UDP-glucuronosyltransferases (UGTs) in neuro-olfactory tissues: expression, regulation, and function. Drug Metab Rev 2010; 42 (1) 74-97
  CrossrefPubMedGoogle Scholar
• 28 Smithson LJ, Kawaja MD. Microglial/macrophage cells in mammalian olfactory nerve fascicles. J Neurosci Res 2010; 88 (4) 858-865
  PubMedGoogle Scholar
• 29 Kelly DE, Wood RL, Enders AC. Bailey's Textbook of Microscopic Anatomy. Baltimore, MD: Williams and Wilkins; 1984
  Google Scholar
• 30 Jafek BW, Murrow B, Michaels R, Restrepo D, Linschoten M. Biopsies of human olfactory epithelium. Chem Senses 2002; 27 (7) 623-628
  CrossrefPubMedGoogle Scholar
• 31 Ross MH, Kaye GI, Pawlina W. Histology: A Text and Atlas. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003
  Google Scholar
• 32 Standring S, Borley NR. Gray's Anatomy: The Anatomical Basis of Clinical Practice. Madrid, Spain: Churchill Livingstone; 2008
  Google Scholar
• 33 Carnicelli V, Santoro A, Sellari-Franceschini S, Berrettini S, Zucchi R. Expression of trace amine-associated receptors in human nasal mucosa. Chemosens Percep 2010; 3 (2) 99-107
  PubMedGoogle Scholar
• 34 Elmas C, Erdoğan D, Ozoğul C. Expression of growth factors in fetal human olfactory mucosa during development. Growth Dev Aging 2003; 67 (1) 11-25
  PubMedGoogle Scholar
• 35 Petruson B, Hansson HA, Karlsson G. Structural and functional aspects of cells in the nasal mucociliary system. Arch Otolaryngol 1984; 110 (9) 576-581
  CrossrefPubMedGoogle Scholar
• 36 Fawcett DW, Raviola E. Bloom and Fawcett, a Textbook of Histology. New York, NY: Chapman & Hall; 1994
  Google Scholar
• 37 Kratzing JE. The anatomy and histology of the nasal cavity of the koala (Phascolarctos cinereus). J Anat 1984; 138 (Pt 1) 55-65
  PubMedGoogle Scholar
• 38 Lovell MA, Jafek BW, Moran DT, Rowley III JC. Biopsy of human olfactory mucosa. An instrument and a technique. Arch Otolaryngol 1982; 108 (4) 247-249
  CrossrefPubMedGoogle Scholar
• 39 Feng WH, Kauer JS, Adelman L, Talamo BR. New structure, the “olfactory pit,” in human olfactory mucosa. J Comp Neurol 1997; 378 (4) 443-453
  CrossrefPubMedGoogle Scholar
• 40 Nakashima T, Kimmelman CP, Snow Jr JB. Structure of human fetal and adult olfactory neuroepithelium. Arch Otolaryngol 1984; 110 (10) 641-646
  CrossrefPubMedGoogle Scholar
• 41 Polyzonis BM, Kafandaris PM, Gigis PI, Demetriou T. An electron microscopic study of human olfactory mucosa. J Anat 1979; 128 (Pt 1) 77-83
  PubMedGoogle Scholar
• 42 Moran DT, Rowley III JC, Jafek BW. Electron microscopy of human olfactory epithelium reveals a new cell type: the microvillar cell. Brain Res 1982; 253 (1–2) 39-46
  CrossrefPubMedGoogle Scholar
• 43 Morrison EE, Costanzo RM. Morphology of olfactory epithelium in humans and other vertebrates. Microsc Res Tech 1992; 23 (1) 49-61
  CrossrefPubMedGoogle Scholar
• 44 Ota Y. Study of the fifth-type cell in the olfactory epithelium. [in Japanese]. Nippon Jibiinkoka Gakkai Kaiho 1998; 101 (10) 1234-1249
  CrossrefPubMedGoogle Scholar
• 45 Schwob JE. Neural regeneration and the peripheral olfactory system. Anat Rec 2002; 269 (1) 33-49
  CrossrefPubMedGoogle Scholar
• 46 Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990; 297 (1) 1-13
  CrossrefPubMedGoogle Scholar
• 47 Bloom G, Engström H. The structure of the epithelial surface in the olfactory region. Exp Cell Res 1952; 3 (4) 699-701
  CrossrefPubMedGoogle Scholar
• 48 Ganong WF. Review of Medical Physiology. 22nd ed. New Yori, NY: McGraw-Hill Medical; 2005
  Google Scholar
• 49 Delay RJ, Dionne VE. Coupling between sensory neurons in the olfactory epithelium. Chem Senses 2003; 28 (9) 807-815
  CrossrefPubMedGoogle Scholar
• 50 Smutzer G, Lee VM, Trojanowski JQ, Arnold SE. Human olfactory mucosa in schizophrenia. Ann Otol Rhinol Laryngol 1998; 107 (4) 349-355
  PubMedGoogle Scholar
• 51 Lee VM, Pixley SK. Age and differentiation-related differences in neuron-specific tubulin immunostaining of olfactory sensory neurons. Brain Res Dev Brain Res 1994; 83 (2) 209-215
  CrossrefPubMedGoogle Scholar
• 52 Choi D, Li D, Law S, Powell M, Raisman G. A prospective observational study of the yield of olfactory ensheathing cells cultured from biopsies of septal nasal mucosa. Neurosurgery 2008; 62 (5) 1140-1144 ; discussion 1144–1145
  CrossrefPubMedGoogle Scholar
• 53 Hahn CG, Han LY, Rawson NE , et al. In vivo and in vitro neurogenesis in human olfactory epithelium. J Comp Neurol 2005; 483 (2) 154-163
  CrossrefPubMedGoogle Scholar
• 54 Takahashi S, Iwanaga T, Takahashi Y, Nakano Y, Fujita T. Neuron-specific enolase, neurofilament protein and S-100 protein in the olfactory mucosa of human fetuses. An immunohistochemical study. Cell Tissue Res 1984; 238 (2) 231-234
  PubMedGoogle Scholar
• 55 Calof AL, Bonnin A, Crocker C , et al. Progenitor cells of the olfactory receptor neuron lineage. Microsc Res Tech 2002; 58 (3) 176-188
  CrossrefPubMedGoogle Scholar
• 56 Pixley SK. CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells. Neuron 1992; 8 (6) 1191-1204
  CrossrefPubMedGoogle Scholar
• 57 Hosaka Y, Yanase H, Iwanaga T. Morphological analysis of olfactory receptor cells using whole-mount preparations of the rat nasal mucosa. J Vet Med Sci 1998; 60 (8) 897-904
  CrossrefPubMedGoogle Scholar
• 58 Witt M, Bormann K, Gudziol V , et al. Biopsies of olfactory epithelium in patients with Parkinson's disease. Mov Disord 2009; 24 (6) 906-914
  CrossrefPubMedGoogle Scholar
• 59 Margolis FL. Olfactory marker protein (OMP). Scand J Immunol Suppl 1982; 9: 181-199
  PubMedGoogle Scholar
• 60 Nakashima T, Kimmelman CP, Snow Jr JB. Olfactory marker protein in the human olfactory pathway. Arch Otolaryngol 1985; 111 (5) 294-297
  CrossrefPubMedGoogle Scholar
• 61 Chuah MI, Zheng DR. Olfactory marker protein is present in olfactory receptor cells of human fetuses. Neuroscience 1987; 23 (1) 363-370
  CrossrefPubMedGoogle Scholar
• 62 Sakai M, Ashihara M, Nishimura T, Nagatsu I. Carnosine-like immunoreactivity in human olfactory mucosa. Acta Otolaryngol 1990; 109 (5–6) 450-453
  CrossrefPubMedGoogle Scholar
• 63 Weiler E, Farbman AI. Supporting cell proliferation in the olfactory epithelium decreases postnatally. Glia 1998; 22 (4) 315-328
  CrossrefPubMedGoogle Scholar
• 64 Hegg CC, Irwin M, Lucero MT. Calcium store-mediated signaling in sustentacular cells of the mouse olfactory epithelium. Glia 2009; 57 (6) 634-644
  CrossrefPubMedGoogle Scholar
• 65 Hempstead JL, Morgan JI. Monoclonal antibodies to the rat olfactory sustentacular cell. Brain Res 1983; 288 (1–2) 289-295
  CrossrefPubMedGoogle Scholar
• 66 Goldstein BJ, Schwob JE. Analysis of the globose basal cell compartment in rat olfactory epithelium using GBC-1, a new monoclonal antibody against globose basal cells. J Neurosci 1996; 16 (12) 4005-4016
  PubMedGoogle Scholar
• 67 Pixley SK, Farbman AI, Menco BP. Monoclonal antibody marker for olfactory sustentacular cell microvilli. Anat Rec 1997; 248 (3) 307-321
  CrossrefPubMedGoogle Scholar
• 68 Minovi A, Witt M, Prescher A , et al. Expression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium. Histol Histopathol 2010; 25 (2) 177-187
  PubMedGoogle Scholar
• 69 Mellert TK, Getchell ML, Sparks L, Getchell TV. Characterization of the immune barrier in human olfactory mucosa. Otolaryngol Head Neck Surg 1992; 106 (2) 181-188
  PubMedGoogle Scholar
• 70 Golgi C. Sulla fina anatomia del bulbi olfattorii. Ti Rivista Sperimentale di Freniatria 1875; 1: 403-425
  PubMedGoogle Scholar
• 71 Blanes T. Sobre algunos puntos dudosos de la estructura del bulbo olfatorio. Rev Trim Micrograf 1898; 3: 99-127
  PubMedGoogle Scholar
• 72 Valverde F, Lopez-Mascaraque L. Neuroglial arrangements in the olfactory glomeruli of the hedgehog. J Comp Neurol 1991; 307 (4) 658-674
  CrossrefPubMedGoogle Scholar
• 73 Doucette R. Glial cells in the nerve fiber layer of the main olfactory bulb of embryonic and adult mammals. Microsc Res Tech 1993; 24 (2) 113-130
  CrossrefPubMedGoogle Scholar
• 74 Barber PC, Lindsay RM. Schwann cells of the olfactory nerves contain glial fibrillary acidic protein and resemble astrocytes. Neuroscience 1982; 7 (12) 3077-3090
  CrossrefPubMedGoogle Scholar
• 75 De Lorenzo AJ. Electron microscopic observations of the olfactory mucosa and olfactory nerve. J Biophys Biochem Cytol 1957; 3 (6) 839-850
  CrossrefPubMedGoogle Scholar
• 76 Peters A, Palay SL, Webster Hde F, de Webster HF. The Fine Structure of the Nervous System: Neurons and Their Supporting Cells. 3th rev. ed. New York, NY: Oxford University Press; 1991
  Google Scholar
• 77 Raisman G. Specialized neuroglial arrangement may explain the capacity of vomeronasal axons to reinnervate central neurons. Neuroscience 1985; 14 (1) 237-254
  CrossrefPubMedGoogle Scholar
• 78 Doucette R. Development of the nerve fiber layer in the olfactory bulb of mouse embryos. J Comp Neurol 1989; 285 (4) 514-527
  CrossrefPubMedGoogle Scholar
• 79 Doucette JR. The glial cells in the nerve fiber layer of the rat olfactory bulb. Anat Rec 1984; 210 (2) 385-391
  CrossrefPubMedGoogle Scholar
• 80 Doucette R. Glial influences on axonal growth in the primary olfactory system. Glia 1990; 3 (6) 433-449
  CrossrefPubMedGoogle Scholar
• 81 Doucette R. PNS-CNS transitional zone of the first cranial nerve. J Comp Neurol 1991; 312 (3) 451-466
  CrossrefPubMedGoogle Scholar
• 82 Mori S, Leblond CP. Electron microscopic features and proliferation of astrocytes in the corpus callosum of the rat. J Comp Neurol 1969; 137 (2) 197-225
  CrossrefPubMedGoogle Scholar
• 83 Kott JN, Westrum LE, Raines EW, Sasahara M, Ross R. Olfactory ensheathing glia and platelet-derived growth factor B-chain reactivity in the transplanted rat olfactory bulb. Int J Dev Neurosci 1994; 12 (4) 315-323
  CrossrefPubMedGoogle Scholar
• 84 Ubink R, Halasz N, Zhang X, Dagerlind Å, Hökfelt T. Neuropeptide tyrosine is expressed in ensheathing cells around the olfactory nerves in the rat olfactory bulb. Neuroscience 1994; 60 (3) 709-726
  CrossrefPubMedGoogle Scholar
• 85 Cummings DM, Brunjes PC. Migrating luteinizing hormone-releasing hormone (LHRH) neurons and processes are associated with a substrate that expresses S100. Brain Res Dev Brain Res 1995; 88 (2) 148-157
  CrossrefPubMedGoogle Scholar
• 86 Gong Q, Bailey MS, Pixley SK, Ennis M, Liu W, Shipley MT. Localization and regulation of low affinity nerve growth factor receptor expression in the rat olfactory system during development and regeneration. J Comp Neurol 1994; 344 (3) 336-348
  CrossrefPubMedGoogle Scholar
• 87 Guenther J, Nick H, Monard D. A glia-derived neurite-promoting factor with protease inhibitory activity. EMBO J 1985; 4 (8) 1963-1966
  PubMedGoogle Scholar
• 88 Zurn AD, Nick H, Monard D. A glia-derived nexin promotes neurite outgrowth in cultured chick sympathetic neurons. Dev Neurosci 1988; 10 (1) 17-24
  CrossrefPubMedGoogle Scholar
• 89 Miragall F, Kadmon G, Husmann M, Schachner M. Expression of cell adhesion molecules in the olfactory system of the adult mouse: presence of the embryonic form of N-CAM. Dev Biol 1988; 129 (2) 516-531
  CrossrefPubMedGoogle Scholar
• 90 Doucette R. Immunohistochemical localization of laminin, fibronectin and collagen type IV in the nerve fiber layer of the olfactory bulb. Int J Dev Neurosci 1996; 14 (7–8) 945-959
  CrossrefPubMedGoogle Scholar
• 91 Kafitz KW, Greer CA. Role of laminin in axonal extension from olfactory receptor cells. J Neurobiol 1997; 32 (3) 298-310
  CrossrefPubMedGoogle Scholar
• 92 Liesi P. Laminin-immunoreactive glia distinguish regenerative adult CNS systems from non-regenerative ones. EMBO J 1985; 4 (10) 2505-2511
  PubMedGoogle Scholar
• 93 Franceschini IA, Barnett SC. Low-affinity NGF-receptor and E-N-CAM expression define two types of olfactory nerve ensheathing cells that share a common lineage. Dev Biol 1996; 173 (1) 327-343
  CrossrefPubMedGoogle Scholar
• 94 Barnett SC, Hutchins A-M, Noble M. Purification of olfactory nerve ensheathing cells from the olfactory bulb. Dev Biol 1993; 155 (2) 337-350
  CrossrefPubMedGoogle Scholar
• 95 Vickland H, Westrum LE, Kott JN, Patterson SL, Bothwell MA. Nerve growth factor receptor expression in the young and adult rat olfactory system. Brain Res 1991; 565 (2) 269-279
  CrossrefPubMedGoogle Scholar
• 96 Boyd JG, Doucette R, Kawaja MD. Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord. FASEB J 2005; 19 (7) 694-703
  CrossrefPubMedGoogle Scholar
• 97 Tomé M, Siladzic E, Santos-Silva A, Barnett SC. Calponin is expressed by subpopulations of connective tissue cells but not olfactory ensheathing cells in the neonatal olfactory mucosa. BMC Neurosci 2007; 8: 74
  CrossrefPubMedGoogle Scholar
• 98 Guérout N, Derambure C, Drouot L , et al. Comparative gene expression profiling of olfactory ensheathing cells from olfactory bulb and olfactory mucosa. Glia 2010; 58 (13) 1570-1580
  PubMedGoogle Scholar
• 99 Rela L, Bordey A, Greer CA. Olfactory ensheathing cell membrane properties are shaped by connectivity. Glia 2010; 58 (6) 665-678
  PubMedGoogle Scholar
• 100 Lakatos A, Franklin RJ, Barnett SC. Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia 2000; 32 (3) 214-225
  CrossrefPubMedGoogle Scholar
• 101 Santos-Silva A, Fairless R, Frame MC , et al. FGF/heparin differentially regulates Schwann cell and olfactory ensheathing cell interactions with astrocytes: a role in astrocytosis. J Neurosci 2007; 27 (27) 7154-7167
  CrossrefPubMedGoogle Scholar
• 102 Tang ZP, Liu N, Li ZW , et al. In vitro evaluation of the compatibility of a novel collagen-heparan sulfate biological scaffold with olfactory ensheathing cells. Chin Med J (Engl) 2010; 123 (10) 1299-1304
  PubMedGoogle Scholar
• 103 Anton ES, Weskamp G, Reichardt LF, Matthew WD. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci U S A 1994; 91 (7) 2795-2799
  CrossrefPubMedGoogle Scholar
• 104 Caggiano M, Kauer JS, Hunter DD. Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron 1994; 13 (2) 339-352
  CrossrefPubMedGoogle Scholar
• 105 Schwob JE. Restoring olfaction: a view from the olfactory epithelium. Chem Senses 2005; 30 (Suppl. 01) i131-i132
  CrossrefPubMedGoogle Scholar
• 106 Farbman AI. Developmental biology of olfactory sensory neurons. Semin Cell Biol 1994; 5 (1) 3-10
  PubMedGoogle Scholar
• 107 Graziadei PPC. Cell dynamics in the olfactory mucosa. Tissue Cell 1973; 5 (1) 113-131
  CrossrefPubMedGoogle Scholar
• 108 Roisen FJ, Klueber KM, Lu CL , et al. Adult human olfactory stem cells. Brain Res 2001; 890 (1) 11-22
  CrossrefPubMedGoogle Scholar
• 109 Lendahl U, Zimmerman LB, McKay RDG. CNS stem cells express a new class of intermediate filament protein. Cell 1990; 60 (4) 585-595
  CrossrefPubMedGoogle Scholar
• 110 Doyle KL, Khan M, Cunningham AM. Expression of the intermediate filament protein nestin by sustentacular cells in mature olfactory neuroepithelium. J Comp Neurol 2001; 437 (2) 186-195
  CrossrefPubMedGoogle Scholar
• 111 Marshall CT, Lu C, Winstead W , et al. The therapeutic potential of human olfactory-derived stem cells. Histol Histopathol 2006; 21 (6) 633-643
  PubMedGoogle Scholar
• 112 Arnold SE, Han L-Y, Moberg PJ , et al. Dysregulation of olfactory receptor neuron lineage in schizophrenia. Arch Gen Psychiatry 2001; 58 (9) 829-835
  CrossrefPubMedGoogle Scholar
• 113 Carter LA, MacDonald JL, Roskams AJ. Olfactory horizontal basal cells demonstrate a conserved multipotent progenitor phenotype. J Neurosci 2004; 24 (25) 5670-5683
  CrossrefPubMedGoogle Scholar
• 114 Leung CT, Coulombe PA, Reed RR. Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci 2007; 10 (6) 720-726
  CrossrefPubMedGoogle Scholar
• 115 Mackay-Sim A, Kittel P. Cell dynamics in the adult mouse olfactory epithelium: a quantitative autoradiographic study. J Neurosci 1991; 11 (4) 979-984
  PubMedGoogle Scholar
• 116 Mumm JS, Shou J, Calof AL. Colony-forming progenitors from mouse olfactory epithelium: evidence for feedback regulation of neuron production. Proc Natl Acad Sci U S A 1996; 93 (20) 11167-11172
  CrossrefPubMedGoogle Scholar
• 117 Graziadei PPC, Graziadei GA. Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons. J Neurocytol 1979; 8 (1) 1-18
  CrossrefPubMedGoogle Scholar
• 118 Huard JM, Youngentob SL, Goldstein BJ, Luskin MB, Schwob JE. Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells. J Comp Neurol 1998; 400 (4) 469-486
  CrossrefPubMedGoogle Scholar
• 119 Lindsay SL, Riddell JS, Barnett SC. Olfactory mucosa for transplant-mediated repair: a complex tissue for a complex injury?. Glia 2010; 58 (2) 125-134
  CrossrefPubMedGoogle Scholar
• 120 Duggan CD, Ngai J. Scent of a stem cell. Nat Neurosci 2007; 10 (6) 673-674
  CrossrefPubMedGoogle Scholar
• 121 Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 2000; 287 (5457) 1442-1446
  CrossrefPubMedGoogle Scholar
• 122 Yamagishi M, Nakamura H, Takahashi S, Nakano Y, Iwanaga T. Olfactory receptor cells: immunocytochemistry for nervous system-specific proteins and re-evaluation of their precursor cells. Arch Histol Cytol 1989; 52 (Suppl): 375-381
  CrossrefPubMedGoogle Scholar
• 123 Jang W, Youngentob SL, Schwob JE. Globose basal cells are required for reconstitution of olfactory epithelium after methyl bromide lesion. J Comp Neurol 2003; 460 (1) 123-140
  CrossrefPubMedGoogle Scholar
• 124 Chen X, Fang H, Schwob JE. Multipotency of purified, transplanted globose basal cells in olfactory epithelium. J Comp Neurol 2004; 469 (4) 457-474
  CrossrefPubMedGoogle Scholar
• 125 Yamagishi M, Nakamura H, Nakano Y, Kuwano R. Immunohistochemical study of the fourth cell type in the olfactory epithelium in guinea pigs and in a patient. ORL J Otorhinolaryngol Relat Spec 1992; 54 (2) 85-90
  CrossrefPubMedGoogle Scholar
• 126 Rowley III JC, Moran DT, Jafek BW. Peroxidase backfills suggest the mammalian olfactory epithelium contains a second morphologically distinct class of bipolar sensory neuron: the microvillar cell. Brain Res 1989; 502 (2) 387-400
  CrossrefPubMedGoogle Scholar
• 127 Miller ML, Andringa A, Evans JE, Hastings L. Microvillar cells of the olfactory epithelium: morphology and regeneration following exposure to toxic compounds. Brain Res 1995; 669 (1) 1-9
  CrossrefPubMedGoogle Scholar
• 128 Murrell W, Féron F, Wetzig A , et al. Multipotent stem cells from adult olfactory mucosa. Dev Dyn 2005; 233 (2) 496-515
  CrossrefPubMedGoogle Scholar
• 129 Delorme B, Nivet E, Gaillard J , et al. The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties. Stem Cells Dev 2010; 19 (6) 853-866
  CrossrefPubMedGoogle Scholar
• 130 Murrell W, Wetzig A, Donnellan M , et al. Olfactory mucosa is a potential source for autologous stem cell therapy for Parkinson's disease. Stem Cells 2008; 26 (8) 2183-2192
  CrossrefPubMedGoogle Scholar
• 131 Gomez G, Rawson NE, Hahn CG, Michaels R, Restrepo D. Characteristics of odorant elicited calcium changes in cultured human olfactory neurons. J Neurosci Res 2000; 62 (5) 737-749
  CrossrefPubMedGoogle Scholar
• 132 Audisio C, Raimondo S, Nicolino S , et al. Morphological and biomolecular characterization of the neonatal olfactory bulb ensheathing cell line. J Neurosci Methods 2009; 185 (1) 89-98
  CrossrefPubMedGoogle Scholar
• 133 Thompson RJ, Roberts B, Alexander CL, Williams SK, Barnett SC. Comparison of neuregulin-1 expression in olfactory ensheathing cells, Schwann cells and astrocytes. J Neurosci Res 2000; 61 (2) 172-185
  CrossrefPubMedGoogle Scholar
• 134 Ramón-Cueto A, Avila J. Olfactory ensheathing glia: properties and function. Brain Res Bull 1998; 46 (3) 175-187
  CrossrefPubMedGoogle Scholar
• 135 Doucette R. Glial progenitor cells of the nerve fiber layer of the olfactory bulb: effect of astrocyte growth media. J Neurosci Res 1993; 35 (3) 274-287
  CrossrefPubMedGoogle Scholar
• 136 Goodman MN, Silver J, Jacobberger JW. Establishment and neurite outgrowth properties of neonatal and adult rat olfactory bulb glial cell lines. Brain Res 1993; 619 (1–2) 199-213
  CrossrefPubMedGoogle Scholar
• 137 Pixley SK. The olfactory nerve contains two populations of glia, identified both in vivo and in vitro. Glia 1992; 5 (4) 269-284
  CrossrefPubMedGoogle Scholar
• 138 Pixley SK. Characterization of olfactory receptor neurons and other cell types in dissociated rat olfactory cell cultures. Int J Dev Neurosci 1996; 14 (7–8) 823-839
  CrossrefPubMedGoogle Scholar
• 139 Chuah MI, Au C. Olfactory Schwann cells are derived from precursor cells in the olfactory epithelium. J Neurosci Res 1991; 29 (2) 172-180
  CrossrefPubMedGoogle Scholar
• 140 Devon R, Doucette R. Olfactory ensheathing cells myelinate dorsal root ganglion neurites. Brain Res 1992; 589 (1) 175-179
  CrossrefPubMedGoogle Scholar
• 141 Gong Q, Liu W-L, Srodon M, Foster TD, Shipley MT. Olfactory epithelial organotypic slice cultures: a useful tool for investigating olfactory neural development. Int J Dev Neurosci 1996; 14 (7–8) 841-852
  CrossrefPubMedGoogle Scholar
• 142 Ramón-Cueto A, Pérez J, Nieto-Sampedro M. In vitro enfolding of olfactory neurites by p75 NGF receptor positive ensheathing cells from adult rat olfactory bulb. Eur J Neurosci 1993; 5 (9) 1172-1180
  CrossrefPubMedGoogle Scholar