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  • Basement Membrane Mimetic Hydrogel Cooperates with Rho‐Associated Protein Kinase Inhibitor to Promote the Development of Acini‐Like Salivary Gland Spheroids
Title: Basement Membrane Mimetic Hydrogel Cooperates with Rho‐Associated Protein Kinase Inhibitor to Promote the Development of Acini‐Like Salivary Gland Spheroids
Successful 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.  more » « less
Award ID(s):
2243648
PAR ID:
10497609
Author(s) / Creator(s):
; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Advanced NanoBiomed Research
Volume:
3
Issue:
11
ISSN:
2699-9307
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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