Faculty, Staff and Student Publications

Publication Date

7-1-2022

Journal

Journal of Dental Research

Abstract

Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar cells, and K19 is the classical ductal marker in salivary tissue. We found that early ductal progenitors derived from hS/PCs do not express K19, and thus earlier markers were needed to distinguish these cells from acinar progenitors. Salivary ductal cells express distinct polarity complex proteins that we hypothesized could serve as lineage biomarkers to distinguish ductal cells from acinar cells in differentiating hS/PC populations. Based on our studies of primary salivary tissue, both parotid and submandibular glands, and differentiating hS/PCs, we conclude that the apical marker MUC1 along with the polarity markers INADL/PATJ and SCRIB reliably can identify ductal cells in salivary glands and in ductal progenitor populations of hS/PCs being used for salivary tissue engineering. Other markers of epithelial maturation, including E-cadherin, ZO-1, and partition complex component PAR3, are present in both ductal and acinar cells, where they can serve as general markers of differentiation but not lineage markers.

Keywords

Acinar Cells, Biomarkers, Cell Differentiation, Cells, Cultured, Epithelial Cells, Humans, Membrane Proteins, Mucin-1, Salivary Glands, Tight Junction Proteins, Tumor Suppressor Proteins, Xerostomia, epithelial cells, glandular, tissue engineering, adult stem cells, cell differentiation, tissue regeneration

DOI

10.1177/00220345221076122

PMID

35259994

PMCID

PMC9266355

PubMedCentral® Posted Date

3-8-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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