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European Archives of... Nov 2009Studies of the tissues of the human olfactory mucosa have been performed to investigate olfactory dysfunction and, more recently, olfactory mucosa has attracted a novel... (Review)
Review
Studies of the tissues of the human olfactory mucosa have been performed to investigate olfactory dysfunction and, more recently, olfactory mucosa has attracted a novel interest of investigators because it can be used as an early marker of neurodegenerative conditions of the brain and as a source of multipotent neural stem cells, with applications in regenerative medicine. The olfactory mucosa is readily available to the otolaryngologist, but the harvesting of this tissue must be safe, effective, and reliable, obtaining as little tissue as necessary, while avoiding unnecessary harm to the remaining olfactory tissue and function. The purpose of this review is to summarize the results of the most important studies and knowledge with regard to the human olfactory mucosa and its applications, emphasizing the issue of the distribution of the olfactory mucosa in the nasal cavities.
Topics: Humans; Olfactory Mucosa
PubMed: 19714350
DOI: 10.1007/s00405-009-1073-x -
Glia Jan 2010Damage to the brain and spinal cord leads to permanent functional disability because of the very limited capacity of the central nervous system (CNS) for repair.... (Review)
Review
Damage to the brain and spinal cord leads to permanent functional disability because of the very limited capacity of the central nervous system (CNS) for repair. Transplantation of cells into regions of CNS damage represents one approach to enhancing this repair. At present, the ideal cell type for transplant-mediated repair has not been identified but autologous transplantation would be advantageous. Olfactory tissue, in part because of its capacity for regeneration, has emerged as a promising source of cells and several clinical centers are using olfactory cells or tissues in the treatment of CNS damage. Until now, the olfactory ensheathing cell, a specialized glial cell of the olfactory system has been the main focus of attention. Transplants of this cell have been shown to have a neuroprotective function, support axonal regeneration, and remyelinate demyelinated axons. However, the olfactory mucosa is a heterogeneous tissue, composed of a variety of cells supporting both its normal function and its regenerative capacity. It is therefore possible that it contains several cell types that could participate in CNS repair including putative stem cells as well as glia. Here we review the cellular composition of the olfactory tissue and the evidence that equivalent cell types exist in both rodent and human olfactory mucosa suggesting that it is potentially a rich source of autologous cells for transplant-mediated repair of the CNS.
Topics: Animals; Brain Injuries; Humans; Nerve Regeneration; Olfactory Mucosa; Olfactory Pathways; Spinal Cord Injuries
PubMed: 19606497
DOI: 10.1002/glia.20917 -
Nature Neuroscience Mar 2020The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying...
The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying input to the olfactory bulbs of the brain. Using single-cell RNA sequencing analyzing 28,726 cells, we identified neural stem cell and neural progenitor cell pools and neurons. Additionally, we detailed the expression of 140 olfactory receptors. These data from the olfactory neuroepithelium niche provide evidence that neuron production may continue for decades in humans.
Topics: Adult; Aging; Humans; Neural Stem Cells; Neurogenesis; Olfactory Mucosa; Olfactory Receptor Neurons; Sequence Analysis, RNA; Single-Cell Analysis; Smell
PubMed: 32066986
DOI: 10.1038/s41593-020-0587-9 -
Microscopy Research and Technique Oct 1992The mucus at the surface of the olfactory mucosa constitutes the milieu in which perireceptor events associated with olfactory transduction occur. In this review, the... (Review)
Review
The mucus at the surface of the olfactory mucosa constitutes the milieu in which perireceptor events associated with olfactory transduction occur. In this review, the ultrastructure of olfactory mucus and of the secretory cells that synthesize and secrete olfactory mucus in the vertebrate olfactory mucosa is described. Bowman's glands are present in the olfactory mucosa of all vertebrates except fish. They consist of acini, which may contain mucous or serous cells or both, and ducts that traverse the olfactory epithelium to deliver secretions to the epithelial surface. Sustentacular cells are present in the olfactory epithelium of all vertebrates. In fish, amphibia, reptiles, and birds, they are secretory; in mammals, they generally are considered to be "non-secretory," although they may participate in the regulation of the mucous composition through micropinocytotic secretion and uptake. Goblet cells occur in the olfactory epithelium of fish and secrete a mucous product. Secretion from Bowman's glands and vasomotor activity in the olfactory mucosa are regulated by neural elements extrinsic to the primary olfactory neurons. Nerve fibers described in early anatomical studies and characterized by immunohistochemical studies contain a variety of neuroactive peptides and have several targets within the olfactory mucosa. Ultrastructural studies of nerve terminals in the olfactory mucosa have demonstrated the presence of adrenergic, cholinergic and peptidergic input to glands, blood vessels, and melanocytes in the lamina propria and of peptidergic terminals in the olfactory epithelium. The neural origins of the extrinsic nerve fibers and terminals are the trigeminal, terminal, and autonomic systems.
Topics: Animals; Humans; Mucus; Olfactory Mucosa
PubMed: 1421551
DOI: 10.1002/jemt.1070230203 -
PloS One 2019Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following...
Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following transplantation, improved locomotion has been detected in many laboratory models and in dogs with naturally-occurring spinal cord injury; safety trials in humans have also been completed. For widespread clinical implementation, it will be necessary to derive large numbers of these cells from an accessible and, preferably, autologous, source making olfactory mucosa a good candidate. Here, we compared the yield of olfactory ensheathing cells from the olfactory mucosa using 3 different techniques: rhinotomy, frontal sinus keyhole approach and rhinoscopy. From canine clinical cases with spinal cord injury, 27 biopsies were obtained by rhinotomy, 7 by a keyhole approach and 1 with rhinoscopy. Biopsy via rhinoscopy was also tested in 13 cadavers and 7 living normal dogs. After 21 days of cell culture, the proportions and populations of p75-positive (presumed to be olfactory ensheathing) cells obtained by the keyhole approach and rhinoscopy were similar (~4.5 x 106 p75-positive cells; ~70% of the total cell population), but fewer were obtained by frontal sinus rhinotomy. Cerebrospinal fluid rhinorrhea was observed in one dog and emphysema in 3 dogs following rhinotomy. Blepharitis occurred in one dog after the keyhole approach. All three biopsy methods appear to be safe for harvesting a suitable number of olfactory ensheathing cells from the olfactory mucosa for transplantation within the spinal cord but each technique has specific advantages and drawbacks.
Topics: Animals; Cell Transplantation; Cells, Cultured; Dogs; Locomotion; Nerve Regeneration; Olfactory Mucosa; Recovery of Function; Spinal Cord Injuries
PubMed: 30840687
DOI: 10.1371/journal.pone.0213252 -
Translational Neurodegeneration Jul 2022In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not...
BACKGROUND
In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.
METHODS
NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.
RESULTS
In the first round, 72 OM samples were collected by NS, from AN (NS) or from MT (NS), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NS samples and in 10/23 (44%) NS samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NS compared to NS. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.
CONCLUSION
In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.
Topics: Humans; Olfactory Mucosa; Parkinson Disease; Smell; Synucleinopathies; alpha-Synuclein
PubMed: 35902902
DOI: 10.1186/s40035-022-00311-3 -
Theranostics 2021Olfactory dysfunctions, including hyposmia and anosmia, affect ~100 million people around the world and the underlying causes are not fully understood. Degeneration of...
Olfactory dysfunctions, including hyposmia and anosmia, affect ~100 million people around the world and the underlying causes are not fully understood. Degeneration of olfactory sensory neurons and incapacity of globose basal cells to generate olfactory sensory neurons are found in elder people and patients with smell disorders. Thus, olfactory stem cell may function as a promising tool to replace inactivated globose basal cells and to generate sensory neurons. We established clonal expansion of cells from the murine olfactory epithelium as well as colony growth from human olfactory mucosa using Matrigel-based three-dimensional system. These colonies were characterized by immunostaining against olfactory epithelium cellular markers and by calcium imaging of responses to odors. Chemical addition was optimized to promote Lgr5 expression, colony growth and sensory neuron generation, tested by quantitative PCR and immunostaining against progenitor and neuronal markers. The differential transcriptomes in multiple signaling pathways between colonies under different base media and chemical cocktails were determined by RNA-Seq. In defined culture media, we found that VPA and CHIR99021 induced the highest Lgr5 expression level, while LY411575 resulted in the most abundant yield of OMP mature sensory neurons in murine colonies. Different base culture media with drug cocktails led to apparent morphological alteration from filled to cystic appearance, accompanied with massive transcriptional changes in multiple signaling pathways. Generation of sensory neurons in human colonies was affected through TGF-β signaling, while Lgr5 expression and cell proliferation was regulated by VPA. Our findings suggest that targeting expansion of olfactory epithelium/mucosa colonies potentially results in discovery of new source to cell replacement-based therapy against smell loss.
Topics: Alanine; Animals; Azepines; Cell Differentiation; Cell Proliferation; Female; Humans; Male; Mice; Neurogenesis; Olfactory Mucosa; Olfactory Receptor Neurons; Pyridines; Pyrimidines; Receptors, G-Protein-Coupled; Stem Cells
PubMed: 33391499
DOI: 10.7150/thno.46750 -
B-ENT 2009The olfactory neuro-epithelium is highly sensitive to chemicals and its direct microbiological environment. It also plays a role as an interface between the airways and... (Review)
Review
The olfactory neuro-epithelium is highly sensitive to chemicals and its direct microbiological environment. It also plays a role as an interface between the airways and the nervous system, and so it has developed several defence instruments for rapid regeneration or for the detoxification of the immediate environment. This review illustrates three of these defence mechanisms: regeneration of the epithelium, local production of metabolising enzymes and xenobiotic transporters. Toxicants can inflict damage by a direct toxic response. Alternatively, they may require metabolic activation to produce the proximate toxicant. In addition to detoxifying inhaled and systemically derived xenobiotics, the local olfactory metabolism may fulfil multiple functions such as the modification of inhaled odorant, the modulation of endogenous signalling molecules and the protection of other tissues such as the CNS and lungs from inhaled toxicants. Finally, the permeability of nasal and olfactory mucosa is an important efficacy parameter for some anti-allergic drugs delivered by intranasal administration or inhalation. Efflux or update transporters expressed in these tissues may therefore significantly influence the pharmacokinetics of drugs administered topically.
Topics: Enzymes; Humans; Membrane Transport Proteins; Neuroepithelial Cells; Olfactory Mucosa; Olfactory Pathways; Regeneration; Smell
PubMed: 20084803
DOI: No ID Found -
Brain, Behavior, and Immunity Jul 2019At the interface of the environment and the nervous system, the olfactory mucosa (OM) is a privileged pathway for environmental toxicants and pathogens towards the...
At the interface of the environment and the nervous system, the olfactory mucosa (OM) is a privileged pathway for environmental toxicants and pathogens towards the central nervous system. The OM is known to produce antimicrobial and immunological components but the mechanisms of action of the immune system on the OM remain poorly explored. IL-17c is a potent mediator of respiratory epithelial innate immune responses, whose receptors are highly expressed in the OM of mice. We first characterized the presence of the IL-17c and its receptors in the OM. While IL-17c was weakly expressed in the control condition, it was strongly expressed in vivo after intranasal administration of polyinosinic-polycytidylic (Poly I:C), a Toll Like Receptor 3 agonist, mimicking a viral infection. Using calcium imaging and electrophysiological recordings, we found that IL-17c can effectively activate OM cells through the release of ATP. In the longer term, intranasal chronic instillations of IL-17c increased the cellular dynamics of the epithelium and promoted immune cells infiltrations. Finally, IL-17c decreased cell death induced by Poly(I:C) in an OM primary culture. The OM is thus a tissue highly responsive to immune mediators, proving its central role as a barrier against airway pathogens.
Topics: Administration, Intranasal; Animals; Female; Immunity, Innate; Immunity, Mucosal; Interleukin-17; Male; Mice; Olfactory Mucosa; Poly I-C; Primary Cell Culture
PubMed: 30776474
DOI: 10.1016/j.bbi.2019.02.012 -
World Neurosurgery Feb 2015To assess clinical methods of sourcing human olfactory ensheathing cells (OECs), and the results of present day clinical studies in OEC transplantation. (Review)
Review
OBJECTIVE
To assess clinical methods of sourcing human olfactory ensheathing cells (OECs), and the results of present day clinical studies in OEC transplantation.
METHODS
Review of literature.
RESULTS
Present clinical studies of OEC transplantation have demonstrated the feasibility and safety of the technique, and no significant complications have occurred from harvest of the olfactory mucosa to culture OECs. These reported studies have not been designed to determine whether clinical outcome is improved by transplantation.
CONCLUSIONS
OEC transplantation strategies need to be studied further. At present clinical models for testing OECs vary in methodology and quality, and until high-quality, well-designed, and sufficiently powered studies have been performed, the true effect of OEC treatment for patients will remain unclear.
Topics: Cadaver; Cells, Cultured; Humans; Immunohistochemistry; Olfactory Mucosa; Spinal Cord Injuries; Tissue and Organ Harvesting
PubMed: 23891878
DOI: 10.1016/j.wneu.2013.07.016