The HBCs are stimulated by pharmacological agents and transplanted into the
nose, where they regenerate the damaged tissues.
published in Stem Cell Reports
led by Dr. James E. Schwob, MD, PhD, who is a Professor of Developmental,
Molecular & Chemical Biology at the Sackler School of Graduate Biomedical
Sciences, Tufts University, Massachusetts, USA.
The first author
of the study was Dr. Jesse Peterson, PhD, who is currently a Postdoctoral
Scientist at the MRC Laboratory of Molecular Biology, Cambridge, UK. Peterson
conducted the study as part of his doctoral thesis while at the Sackler School of
Graduate Biomedical Sciences, Tufts University, working under the supervision
What's Unique About the Nerve Cells in the
The uniqueness of
the neuronal cells responsible for the sense of smell lies in the fact that
they have an inherent capacity to regenerate, following an injury. No other
nerve cells in the nervous system exhibit this property. This regenerative
capacity arises from the presence of two types of stem cells in the olfactory
epithelium - globose basal cells (GBC)
The GBCs can be
easily cultured and their primary role is to repopulate cells that have been
lost by the natural process of cell turnover. The HBCs normally remain dormant
and are only activated following an injury. Contrary to GBCs, it has not been possible
to culture HBCs as they cannot be expanded and maintained in culture.
In this study,
team has succeeded in culturing healthy HBCs by establishing
the optimal conditions required for expanding and maintaining these cells in
culture. This was made possible by following a protocol similar to that used
for culturing respiratory stem cells.
"Once we determined that we could grow HBCs in the
lab, and that they expressed the same identifying molecular markers found in
vivo, we sought to confirm whether they would work as well as the in vivo HBCs
- can they regenerate tissue that has been injured - and they did!"
What are the Reasons for Alteration of the
Sense of Smell?
Despite the high
regenerative capacity of the olfactory epithelium, dysfunctions in the sense of smell
can occur. It has been reported in the OLFACAT Study (2012) that the prevalence
of smell dysfunction is 19.4 percent - 0.3 percent with a complete loss of smell (anosmia)
19.1 percent with a partial loss of smell (hyposmia).
factors have been found to be responsible for smell dysfunction:
respiratory tract infection
- Polyps in the nasal cavity
of certain medicines
How Did the Stem Cells Differentiate into
The researchers found
that the cultured HBCs were capable for repopulating the olfactory lesions by
regenerating multiple cell types of the olfactory epithelium, including
sustentacular (Sus) cells, basal cells, microvillar (MV) cells, and olfactory
sensory neurons (OSN).
Retinoic acid was
used to stimulate the HBCs to undergo differentiation, by lowering the levels
on an intracellular protein called P63 present within the HBCs, which resulted
in their activation. The P63 protein functions as a 'Master Switch' as
fluctuation in its level within cells can produce different physiological
effects. For example, following injury, P63 levels decrease, which switches the
HBCs from a dormant to an active state.
In this regard,
Peterson says: "The HBCs in culture
remained quiescent, pretty much as they do in vivo, but we were able to trigger
them into an active state to start the process of differentiation into various
olfactory epithelial cells just before engrafting them into injured tissue."
could open new avenues for developing novel therapies based on stem cell
transplantation that could, in the future, be able to restore the sense of
smell in persons where it has been lost due to degeneration or injury.
"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 - using the patient's own stem
cells for culturing and transplantation, or pharmacological interventions to
activate the patient's own dormant stem cells within the nose."
The study was
funded by the National Institutes of Health's National Institute on Deafness
and Other Communication Disorders (NIDCD), Bethesda, Maryland, USA. Reference :
- Cultured Stem Cells Reconstruct Sensory Nerve and Tissue Structure in the Nose - (https://now.tufts.edu/news-releases/cultured-stem-cells-reconstruct-sensory-nerve-and-tissue-structure-nose)