Olfactory models as a platform for neuroscience research

The capacity of the olfactory epithelium (OE) to sustain adult neurogenesis offers an unprecedented opportunity to investigate the mechanisms of neural lineage specification, cellular turnover, and tissue regeneration in a human context. Unlike conventional brain organoids, which predominantly model embryonic or fetal neurodevelopment, olfactory organoid systems uniquely provide experimental access to active adult human neurogenic and regenerative dynamics. As the only accessible adult neural stem cell niche that can be repeatedly sampled from living patients, this neuroepithelium opens new paths for generating patient-specific, non-reprogrammed neural models. This review provides an overview of OE-derived in vitro systems, detailing their evolution from early neurospheres to advanced three-dimensional (3D) organoids, highlighting their capacity to preserve donor genetic, epigenetic, transcriptomic and proteomic signatures, establishing them as a powerful platform for personalized medicine, disease modeling, and “nose-to-brain” therapeutic discovery.