Pediatric Human Olfactory Epithelium Mirrors Adult Structure and Function in a Human Olfactory Organoid Model.

OBJECTIVE

This study investigated the developmental differences in structure, gene expression, and function of human olfactory epithelium (OE) using pediatric and adult specimens and human olfactory organoids.

BACKGROUND

Olfactory dysfunction (OD) is characterized by loss or alterations in the sense of smell and has an age-related increase in prevalence. Murine models have demonstrated stable expression of olfactory receptors in the OE over time, pointing toward OE cell density as a potential driver of age-related OD. Developmental changes in human OE remain poorly characterized. Herein we assess the structure and function of human OE across the lifespan to better understand normal maturation and age-related degeneration.

METHODS

Superior turbinate biopsies from pediatric and adult subjects were obtained for the culture of three-dimensional olfactory organoids. Immunofluorescence (IF) and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) were performed to confirm the structural make-up and gene expression of expected OE cell types. Live-cell calcium imaging was performed to assess organoid response to odorants, a surrogate of function.

RESULTS

IF confirmed that pediatric and adult organoids contain major OE cell populations (e.g., horizontal and globose basal cells, sustentacular cells, and immature and mature olfactory sensory neurons). There was no statistical difference in OE cell gene expression between pediatric and adult tissue. Calcium imaging demonstrated no significant difference in odorant-evoked responses (peak amplitude, area under the curve).

CONCLUSION

Human OE appears structurally, transcriptionally, and functionally stable across the lifespan under the conditions assessed in this organoid model. Further research is needed to better understand age-related OD, which may stem from non-OE-derived changes.