Restoring a sense of smell with stem cells

Activated HBCs differentiate into neurons (red) and non-neuronal supporting cells (gold) of the olfactory epithelium. (Jim Schwob/Tufts University in Stem Cell Reports)

The sense of smell is important for people: It helps us detect harmful odors, affects our appetite, and induces reactions such as memories and emotions. But all of that can be hampered by aging, injury, chronic sinus diseases and neurodegenerative disorders.

The inability or decreased ability to smell, known as anosmia and hyposmia respectively, is not always treatable. Now researchers at Tufts University School of Medicine have shown they can restore the sense of smell by growing and activating olfactory stem cells in culture. The technique could be used to regenerate nose tissue, including sensory neurons, they say.

The olfactory epithelium, which is the sheet of tissue with neurons and supporting cells that lines the nasal cavity, has two types of stem cells: globose basal cells (GBCs) and horizontal basal cells (HBCs). GBCs mainly play a role in the routine replenishment of nasal cells, and they have been successfully cultured. HBCs, on the other hand, remain dormant unless activated by tissue injury. HBCs have proven difficult to maintain in culture, limiting scientists' ability to research them. The Tufts team described how to culture HBCs in a study published in the journal Stem Cell Reports.

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The researchers took their lead from the conditions used to culture respiratory stem cells. From there, they directed the stem cells to differentiate into olfactory epithelial cells such as Sus cells, basal cells and olfactory sensory neurons, before engrafting them into injured tissue. 

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Even though the olfactory epithelium has a natural ability to regenerate, serious injuries can trigger a permanent loss of smell. A 2016 NIH-backed study based on the U.S. National Health and Nutrition Examination Survey found that smell dysfunction affects around 12.4% of adults, and that 3.2% of people have a complete or severe loss.

The Tufts research was led by James Schwob, M.D., Ph.D., a professor of developmental molecular and chemical biology, who previously led a team that showed that a protein called p63 is “a master regulator” involved in the activation of HBCs. They discovered that lowering levels of p63 is necessary for HBC activation, so for this study they used retinoic acid to dial down levels of the protein. 

Schwob and colleagues believe their findings open the door to future research into stem cell therapies that could help patients suffering from a loss of smell.

“Now that we can create a reserve of dormant stem cells, we see this as a useful tool for exploring ways to guide cell differentiation toward specific cell types, and develop new stem cell therapies for tissue and sensory regeneration […] or pharmacological interventions to activate the patient's own dormant stem cells within the nose,” Schwob said in a statement.

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