Stem Cell Niches for Olfactory Regeneration and Their Therapeutic Applications

Olfactory dysfunction affects many individuals and may result from infections, trauma, neurodegenerative diseases, or genetic disorders. Unlike most neurons in the mammalian nervous system, olfactory sensory neurons (OSNs) continuously regenerate throughout life, a process facilitated by specialized stem cell niches in the olfactory epithelium. Horizontal basal cells are typically dormant under normal conditions but become activated following injury, differentiating into globose basal cells (GBCs) and other cell types. GBCs serve as the primary source for OSN regeneration and are regulated by key transcription factors such as Sox2, Pax6, and Ascl1. Olfactory ensheathing cells play a vital role in regeneration by guiding newly formed axons toward the olfactory bulb and secreting neurotrophic factors, including glial cell-derived neurotrophic factor. In addition, the olfactory bulb synthesizes trophic factors like brain-derived neurotrophic factor and nerve growth factor, which support neuronal survival and integration. Despite this intrinsic regenerative capacity, many cases of olfactory dysfunction remain challenging to treat. Current therapeutic strategies include corticosteroids, biologics, surgical interventions, and olfactory training, although their effectiveness varies. Advances in molecular and cellular research have provided insights into the regulatory mechanisms of olfactory neurogenesis, underscoring the need for further exploration of stem cell activation, neuronal survival, and olfactory circuit reorganization. Future research should focus on optimizing regenerative therapies-including stem cell-based approaches and neurotrophic factor modulation-to improve outcomes for patients with severe olfactory impairment.