Human Salivary Gland Stem/Progenitor Cells for Tissue Engineering, SARS-CoV-2 Susceptibility, and Neurointegration

<p>Salivary glands and the saliva they secrete are important for digestion, chewing, and maintaining oral health. Reduced saliva production leads to a decreased quality of life for patients experiencing hyposalivation as a result of disease or injury, thus a large effort has been dedicated to developing materials and medium to recapitulate the structure of the gland for regenerative medicine. In doing so, we have come closer to developing a more complex model to study disease. These models, however, do not yet fully recapitulate the gland. In this dissertation, we describe a new cell source that can be used to develop tissue engineered salivary glands that are readily accessible through a minor incision of the lip. We then use these minor-gland derived salivary gland stem progenitor cells (hS/PCs) along with those isolated from major glands to understand salivary gland susceptibility to SARS-CoV-2, while also contributing data on mechanisms that might explain the ability of coronaviruses to infect salivary glands in the absence of its canonical receptor ACE2, which we conclusively showed is not present in salivary tissue or the basal cells of the ducts. Finally, we detail methods for co-culture of neural cells and salivary cells, including two different stem cell sources that can be differentiated into neural cells. This work also details methods used to create hyaluronic acid (HA) hydrogels that support the co-culture of hS/PCs and neural cells, with a focus on modifications to the hydrogels that allow forming neurites to traverse the material to form neural networks. Taken together, this work contributes new cell types and new methods for increasing the complexity of 3D tissue engineered salivary glands that can be used to better understand the normal functions and pathology of salivary glands.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2025

Authors dc:creator

• Barrows, Caitlynn
• <p>https://orcid.org/0000-0003-4696-9354</p>

Contributors dc:contributor

• Simon Young
• Mary C. Farach-Carson
• Kartik Venkatachalam

• Salivary Glands
• SARS-CoV-2
• Innervation
• Stem Cells
• Biology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1464

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2521