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Updated: Jul 25, 2025
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Genetic Modification and Recombination of Salivary Gland Organ Cultures
Published on: January 28, 2013
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Matrix Degradability Contributes to the Development of Salivary Gland Progenitor Cells with Secretory Functions
Apoorva S Metkari1, Eric W Fowler1, Robert L Witt2
1Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716, United States.
ACS Applied Materials & Interfaces
|June 26, 2023
Summary
Synthetic hydrogels that degrade over time promote the growth and development of salivary gland stem cells. This cell-mediated matrix remodeling is crucial for engineering functional salivary gland constructs to treat dry mouth.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Development of implantable salivary gland constructs is needed to treat radiation-induced xerostomia.
- Cytocompatible, cell-adhesive, and cell-responsive synthetic matrices are essential for this purpose.
Purpose of the Study:
- To engineer hydrogels with varying degradability using bioorthogonal Michael-type addition reactions.
- To investigate the impact of matrix degradability on human salivary gland stem cell (hS/PC) proliferation, organization, and differentiation.
Main Methods:
- Synthesized hydrogels using thiolated hyaluronic acid (HA-SH), maleimide (MI)-conjugated RGD peptide (RGD-MI), and MI-functionalized peptide cross-linkers (protease-degradable GIW-bisMI or nondegradable GIQ-bisMI).
- Incorporated varying degrees of matrix metalloproteinase (MMP)-degradability (0%, 50%, 100%).
- Cultured primary human salivary gland stem cells (hS/PCs) within the hydrogels and analyzed cell proliferation, structure, and marker expression (CD44, K5, α-amylase, KIT, KRT5, ETV4/5, AMY, AQP5, SLC12A2) via immunocytochemistry, mRNA, and Western blot analyses.
Main Results:
- Organized multicellular structures formed in all hydrogels; increased matrix degradability promoted cell proliferation and larger, more lobular structures.
- Stem/progenitor cell markers (CD44, K5, KIT, KRT5, ETV4/5) were upregulated in degradable hydrogels compared to nondegradable ones.
- Degradable matrices (50% and 100%) supported the expression of the acinar marker α-amylase, indicating promotion of a secretory phenotype.
Conclusions:
- Cell-mediated matrix remodeling within MMP-degradable hydrogels is essential for the development of regenerative pro-acinar progenitor cells from hS/PCs.
- Tailoring hydrogel degradability offers a strategy to control stem cell behavior and engineer functional salivary gland constructs for xerostomia treatment.
