Stem Cells of the Adult Olfactory Epithelium

Intranasal administration is a promising route of delivery of stem cells to the central nervous system (CNS). Reports on this mode of stem cell delivery have not yet focused on the route across the cribriform plate by which cells move from the nasal cavity into the CNS. In the current experiments, human mesenchymal stem cells (MSCs) were isolated from Wharton’s jelly of umbilical cords and were labeled with extremely bright quantum dots (QDs) in order to track the cells efficiently. At 2 h after intranasal delivery in immunodeficient mice, the labeled cells were found under the olfactory epithelium, crossing the cribriform plate adjacent to the fila olfactoria, and associated with the meninges of the olfactory bulb. At all times, the cells were separate from actual nerve tracts; this location is consistent with them being in the subarachnoid space (SAS) and its extensions through the cribriform plate into the nasal mucosa. In their location under the olfactory epithelium, they appear to be within an expansion of a potential space adjacent to the turbinate bone periosteum. Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.

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Effects of Systemic Transplantation of Adipose Tissue-Derived Stem Cells on Olfactory Epithelium Regeneration

Yearbook of Otolaryngology-Head and Neck Surgery ◽

10.1016/s1041-892x(10)79636-0 ◽

2010 ◽

Vol 2010 ◽

pp. 195-198

Author(s):

R. Sindwani

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Olfactory Epithelium ◽

Epithelium Regeneration

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Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1620664114 ◽

2017 ◽

Vol 114 (30) ◽

pp. 8089-8094 ◽

Cited By ~ 26

Author(s):

Mengfei Chen ◽

Randall R. Reed ◽

Andrew P. Lane

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Olfactory Epithelium ◽

Acute Inflammation ◽

Basal Layer ◽

Basal Cells ◽

Genetic Ablation ◽

Molecular Events ◽

Tnf Α ◽

Horizontal Basal Cells

Adult neural stem cells/progenitor cells residing in the basal layer of the olfactory epithelium are capable of reconstituting the neuroepithelium even after severe damage. The molecular events underlying this regenerative capacity remain elusive. Here we show that the repair of neuroepithelium after lesioning is accompanied by an acute, but self-limited, inflammatory process. Attenuation of inflammatory cell recruitment and cytokine production by dexamethasone impairs proliferation of progenitor horizontal basal cells (HBCs) and subsequent neuronal differentiation. Using TNF-α receptor-deficient mice, we identify TNF-α signaling as an important contributor to this inflammatory and reparative process, mainly through TNF-α receptor 1. HBC-selective genetic ablation of RelA (p65), the transcriptional activator of the NF-κB pathway, retards inflammation and impedes proliferation at the early stages of regeneration and suggests HBCs directly participate in cross-talk between immune response and neurogenesis. Loss of RelA in the regenerating neuroepithelium perturbs the homeostasis between proliferation and apoptosis while enhancing JNK signaling. Together, our results support a model in which acute inflammation after injury initiates important regenerative signals in part through NF-κB–mediated signaling that activates neural stem cells to reconstitute the olfactory epithelium.

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Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1512272112 ◽

2015 ◽

Vol 112 (36) ◽

pp. E5068-E5077 ◽

Cited By ~ 37

Author(s):

Nikolai Schnittke ◽

Daniel B. Herrick ◽

Brian Lin ◽

Jesse Peterson ◽

Julie H. Coleman ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Olfactory Epithelium ◽

Tissue Injury ◽

Cell Types ◽

Stem Cell Population ◽

Basal Cells ◽

Loss Of Function ◽

Down Regulation ◽

Horizontal Basal Cells

Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs.

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Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures

Gene Expression Patterns ◽

10.1016/j.gep.2015.12.002 ◽

2016 ◽

Vol 20 (1) ◽

pp. 71-79 ◽

Cited By ~ 2

Author(s):

Jennifer L. Baker ◽

Bernard Wood ◽

Beverly A. Karpinski ◽

Anthony-S. LaMantia ◽

Thomas M. Maynard

Keyword(s):

Stem Cells ◽

Olfactory Epithelium ◽

Skeletal Structures ◽

Testicular Receptor

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Centrioles are amplified via rosette formation in cycling progenitors of olfactory sensory neurons

10.1101/695098 ◽

2019 ◽

Author(s):

Kaitlin Ching ◽

Tim Stearns

Keyword(s):

Stem Cells ◽

Embryonic Development ◽

Sensory Neurons ◽

Olfactory Epithelium ◽

Rosette Formation ◽

Olfactory Sensory Neurons ◽

Centriole Duplication ◽

Neuronal Precursors ◽

Neuron Regeneration

AbstractOlfaction in most animals is mediated by neurons bearing cilia that are accessible to the environment. Olfactory sensory neurons (OSNs) in chordates usually have multiple cilia, each with a centriole at its base. OSNs differentiate from stem cells in the olfactory epithelium, and how the epithelium generates cells with many centrioles—about 16 in mouse—is not yet understood. We show that centrioles are amplified via centriole rosette formation in both embryonic development and turnover of the olfactory epithelium in adults, and rosette-bearing cells often have free centrioles in addition. Cells with amplified centrioles can go on to divide, with centrioles clustered at each pole. Additionally, we found that immediate neuronal precursors amplify centrioles concomitantly with elevation of mRNA for Plk4 and Stil, key regulators of centriole duplication. Our findings highlight the importance of accounting for centriole amplification in neuron regeneration therapies derived from olfactory epithelia.

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