Strategies to Develop Regenerative Medicine Approaches for Olfactory Disorders

Olfactory loss affects more than 12% of the population, with prevalence increasing in aging individuals. Multiple conditions can lead to a loss of smell (hyposmia or anosmia), including post-viral damage from coronavirus disease 2019 (COVID-19) or influenza, head injuries, sinusitis, or neurodegenerative conditions such as Alzheimer or Parkinson disease. Although treatments like surgery, anti-inflammatory medications, or olfactory training can be beneficial in certain cases, there remains an unmet need for effective therapies addressing many common causes of olfactory dysfunction. This is particularly true for cases attributed to damage of olfactory neurons that fail to spontaneously recover. Regenerative medicine approaches, aimed at either stimulating the regrowth of sensory neural structures or replacing them through cell-based therapies, have attracted considerable interest for treating various neurological disorders, including olfactory loss. Here, we summarize the intrinsic regenerative capabilities of the peripheral olfactory system, focusing on current research strategies and the existing barriers that must be overcome for successful translational applications. A major unmet need in this field involves the establishment of reliable and widely accepted culture models for expanding and differentiating olfactory stem or progenitor cells from rodents and humans, both for use in vitro assays and as potential material for cell-based therapies.