Strategies towards development of regenerative medicine approaches for olfactory disorders.

Abstract

Olfactory loss impacts >12% of the population and increases with aging. Multiple conditions can cause loss of smell (hyposmia or anosmia), including post-viral damage from COVID-19 or influenza, head injuries, sinusitis, or neurodegenerative conditions such as Alzheimer's or Parkinson's disease. While treatments including surgery, anti-inflammatories or olfactory training may be of benefit in specific cases, there is an unmet need for effective therapies for many common causes of olfactory dysfunction, especially those thought to be due to damage to the olfactory neurons that have failed to recover spontaneously. Regenerative medicine approaches, to either stimulate re-growth of sensory neural structures or to replace them via cell-based therapies, have been a subject of interest for many neurologic disorders, including olfactory loss. Here, we summarize the normal regenerative properties of the peripheral olfactory system and focus on current research strategies, along with barriers to be addressed for successful translational applications. A major unmet need for the field involves establishment of well-accepted culture models to expand and differentiate olfactory stem or progenitor cells from rodents and humans, for both in vitro assays and potential material for cell-based therapies.