2. Academic Validation
  3. Human iPSC-derived salivary gland organoids model diabetic salivary gland dysfunction

Human iPSC-derived salivary gland organoids model diabetic salivary gland dysfunction

  • bioRxiv. 2025 Oct 3:2025.10.01.679897. doi: 10.1101/2025.10.01.679897.
Devon Duron Ehnes 1 2,  Akira Morishita 2 3,  Ashish Phal 2 4,  Hee Yun Jung 2 4,  Yen Chian Lim 1 2,  Zachary Foreman 1 2,  Vincenzo Cirulli 2 5,  Julie Mathieu 2 6,  Hannele Ruohola-Baker 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • 2 Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
  • 3 Department of Biology, University of Washington, Seattle, WA, USA.
  • 4 Department of Bioengineering, University of Washington, Seattle, WA, USA.
  • 5 Departments of Medicine and Pharmacology, UW Diabetes Institute, University of Washington, Seattle, WA USA.
  • 6 Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
PMID: 41256700 DOI: 10.1101/2025.10.01.679897
Abstract

Salivary glands are highly susceptible to injury and degeneration. To facilitate studies in human salivary gland disease, we developed a rapid protocol for 3D hiPSC-derived salivary gland organoids that recapitulate human fetal salivary gland gene expression and function, have both ductal and acinar cell types, secretory capacity, and the ability to respond to cholinergic agonism. Oral health issues resulting from diabetes mellitus have been attributed to salivary gland dysfunction, leading to chronic xerostomia and increased dental caries. To study diabetic salivary gland hypofunction, we further developed a diabetic model, demonstrating diabetic hallmarks including FOXO1 nuclear localization, AGE-RAGE signaling, and defective Oxidative Phosphorylation, which were by treatment with the diabetic drug Metformin. Our model has implications for the development of effective therapeutics against salivary gland dysfunction in diabetes and Other metabolic diseases in exocrine tissues.

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