Basement Membrane Mimetic Hydrogel Cooperates with Rho-Associated Protein Kinase Inhibitor to Promote the Development of Acini-Like Salivary Gland Spheroids

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Author(s)Fowler, Eric W.
Author(s)Witt, Robert L.
Author(s)Jia, Xinqiao
Date Accessioned2024-02-06T18:51:35Z
Date Available2024-02-06T18:51:35Z
Publication Date2023-11-20
DescriptionThis article was originally published in Advanced NanoBiomed Research. The version of record is available at: https://doi.org/10.1002/anbr.202300088. © 2023 The Authors. Advanced NanoBiomed Research published by Wiley-VCH GmbH.
AbstractSuccessful engineering of functional salivary glands necessitates the creation of cell-instructive environments for ex vivo expansion and lineage specification of primary human salivary gland stem cells (hS/PCs). Herein, basement membrane mimetic hydrogels are prepared using hyaluronic acid, cell adhesive peptides, and hyperbranched polyglycerol (HPG), with or without sulfate groups, to produce “hyperGel+” or “hyperGel”, respectively. Differential scanning fluorescence experiments confirm the ability of the sulfated HPG precursor to stabilize fibroblast growth factor 10. The hydrogels are nanoporous, cytocompatible, and cell-permissive, enabling the development of multicellular hS/PC spheroids in 14 days. The incorporation of sulfated HPG species in the hydrogel enhances cell proliferation. Culture of hS/PCs in hyperGel+ in the presence of a Rho kinase inhibitor Y-27632 (Y-27) leads to the development of spheroids with a central lumen, increases the expression of acinar marker aquaporin-3 at the transcript level (AQP3), and decreases the expression of ductal marker keratin 7 at both the transcript (KRT7) and the protein levels (K7). Reduced expression of transforming growth factor beta (TGF-β) targets SMAD2/3 is also observed in Y27-treated cultures, suggesting attenuation of TGF-β signaling. Thus, hyperGel+ cooperates with the Rho-associated protein kinase inhibitor to promote the development of lumened spheroids with enhanced expression of acinar markers.
SponsorThis work was supported in part by the National Institutes of Health (NIDCR R01 DE029655, NIDCD, R01DC014461), National Science Foundation (NSF, DMR 2243648), and Delaware Bioscience Center for Advanced Technology (DE-CAT 12A00448). The authors also acknowledge the use of facilities and instrumentation supported by NSF through the University of Delaware Materials Research Science and Engineering Center (DMR 2011824). Microscopy access was supported by grants from the NIH-NIGMS (P20 GM103446), the NSF (IIA-1301765), and the State of Delaware. The authors thank Drs. Jeffrey Caplan and Sylvain Le Marchand for their expert assistance in confocal imaging and image analysis. The authors thank Sanofi/Genzyme for generously providing HA.
CitationFowler, E.W., Witt, R.L. and Jia, X. (2023), Basement Membrane Mimetic Hydrogel Cooperates with Rho-Associated Protein Kinase Inhibitor to Promote the Development of Acini-Like Salivary Gland Spheroids. Adv. NanoBiomed Res., 3: 2300088. https://doi.org/10.1002/anbr.202300088
ISSN2699-9307
URLhttps://udspace.udel.edu/handle/19716/33948
Languageen_US
PublisherAdvanced NanoBiomed Research
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
Keywordshyaluronic acid
Keywordshyperbranched polyglycerol
KeywordsRho-associated protein kinase inhibitor
Keywordssalivary gland
Keywordsstem/progenitor cells
TitleBasement Membrane Mimetic Hydrogel Cooperates with Rho-Associated Protein Kinase Inhibitor to Promote the Development of Acini-Like Salivary Gland Spheroids
TypeArticle
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