Olfactory Swab-Derived Human Neuroepithelium Cell Culture as a Novel Model to Study Neurodegeneration-Related Proteins.
- 1Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.
- 2Department of Surgery, Dentistry, Paediatrics and Gynaecology, Otolaryngology Section, University of Verona, 37134 Verona, Italy.
Abstract
The olfactory neuroepithelium (ON) collected with nasal swabs (NS) is a valuable source for studying brain processes in physiological and pathological conditions, due to its anatomical proximity to the brain and heterogeneous neural cell population. In this proof-of-concept study, we developed a protocol for co-culturing distinct cellular populations from ON, establishing a human olfactory neuroepithelium cell culture (hON) model from healthy individuals (HIs) without differentiation factors. We characterized the cellular composition of ON samples at harvesting, identifying sustentacular cells (Pan-CK⁺), neuronal cells (PGP9.5⁺), and ciliated respiratory cells (βIV-tubulin⁺) by immunofluorescence and flow cytometry. We assessed the expression and distribution of TDP-43, Tau, and α-synuclein, together with their phosphorylated isoforms, to establish a physiological reference profile. Furthermore, Seeding Amplification Assay (SAA) analysis, including disease-positive and healthy control cohorts, confirmed the absence of aggregated protein species in HIs. While p-Tau and p-α-syn localization was preserved between collection and culture, p-TDP-43 displayed neuron-specific nuclear redistribution upon culture, suggesting distinct regulatory dynamics. Longitudinal monitoring revealed that hON cultures maintain a stable neuronal population for up to 21 days, after which cells transition toward a fibroblast-like phenotype. This study establishes NS-derived hON as a feasible model for investigating neurodegenerative mechanisms, providing a baseline for disease comparisons.
Related
- Staphylococcus aureus‐derived xanthine exacerbates allergic rhinitis‐induced olfactory dysfunction through promoting Th17 cell differentiation and IL‐17A production
- Transcriptional coupling of metabolism and cell mechanics controls human neuroepithelium morphogenesis
- Increased EV yield and bioactivity of matrix-bound nanovesicles compared to conditioned culture medium-derived extracellular vesicles
- Roles of endogenous retrovirus- and other LTR retrotransposon-derived proteins and peptides in neurological disorders, oncogenesis, and host defense
- Characterization of stereolithography 3D-printed chips with different resins and post-treatments for the culture of hiPSC-derived motor neurons
BibTeX
@article{silvestri2026olfactory,
title = {{Olfactory Swab-Derived Human Neuroepithelium Cell Culture as a Novel Model to Study Neurodegeneration-Related Proteins.}},
author = {Francesco Silvestri and Erika Bronzato and Ilaria Scambi and Valerio Arietti and Luca Sacchetto and Raffaella Mariotti and Gianluigi Zanusso and Matilde Bongianni and Ermanna Turano},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15191824},
url = {https://europepmc.org/article/MED/42882522},
note = {CC BY},
}
RIS
TY - JOUR
TI - Olfactory Swab-Derived Human Neuroepithelium Cell Culture as a Novel Model to Study Neurodegeneration-Related Proteins.
AU - Francesco Silvestri
AU - Erika Bronzato
AU - Ilaria Scambi
AU - Valerio Arietti
AU - Luca Sacchetto
AU - Raffaella Mariotti
AU - Gianluigi Zanusso
AU - Matilde Bongianni
AU - Ermanna Turano
PY - 2026
DA - 2026/10/07
JO - Cells
DO - 10.3390/cells15191824
UR - https://europepmc.org/article/MED/42882522
AB - The olfactory neuroepithelium (ON) collected with nasal swabs (NS) is a valuable source for studying brain processes in physiological and pathological conditions, due to its anatomical proximity to the brain and heterogeneous neural cell population. In this proof-of-concept study, we developed a protocol for co-culturing distinct cellular populations from ON, establishing a human olfactory neuroepithelium cell culture (hON) model from healthy individuals (HIs) without differentiation factors. We characterized the cellular composition of ON samples at harvesting, identifying sustentacular cells (Pan-CK⁺), neuronal cells (PGP9.5⁺), and ciliated respiratory cells (βIV-tubulin⁺) by immunofluorescence and flow cytometry. We assessed the expression and distribution of TDP-43, Tau, and α-synuclein, together with their phosphorylated isoforms, to establish a physiological reference profile. Furthermore, Seeding Amplification Assay (SAA) analysis, including disease-positive and healthy control cohorts, confirmed the absence of aggregated protein species in HIs. While p-Tau and p-α-syn localization was preserved between collection and culture, p-TDP-43 displayed neuron-specific nuclear redistribution upon culture, suggesting distinct regulatory dynamics. Longitudinal monitoring revealed that hON cultures maintain a stable neuronal population for up to 21 days, after which cells transition toward a fibroblast-like phenotype. This study establishes NS-derived hON as a feasible model for investigating neurodegenerative mechanisms, providing a baseline for disease comparisons.
SN - 2073-4409
ER -