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Functional Human Salivary Gland Organoids for Tissue Regeneration in Chemically Defined Culture Systems

ABSTRACT: Salivary gland dysfunction significantly impairs patients' quality of life, yet effective regenerative therapies remain clinically unavailable. In this study, we established a fully chemically defined, xeno-free three-dimensional culture system to generate functional human salivary gland organoids. These organoids recapitulate the typical glandular architecture and display multilineage cellular composition, supporting long-term expansion with high transcriptomic fidelity to the primary tissue.functional assays demonstrated that the organoids exhibit key salivary functions, including glycoprotein secretion, amylase expression, and calcium flux in response to cholinergic stimulation. Single-cell transcriptomic analysis revealed preserved epithelial heterogeneity within the organoids and uncovered a basal-to-ductal-to-acinar bifurcated differentiation trajectory. In vivo transplantation into Sjögren’s syndrome mouse models resulted in significantly improved salivary secretion, accompanied by structural reconstruction and vascularization in both orthotopic and ectopic settings. Collectively, this study establishes a robust, functionally mature, and clinically translatable human salivary gland organoid system, offering a promising platform for tissue regeneration therapies targeting salivary hypofunction disorders such as Sjögren’s syndrome.

ORGANISM(S): Mus Musculus

SUBMITTER: Zhigang Cai

PROVIDER: PXD066438 | iProX | Tue Jul 22 00:00:00 BST 2025

REPOSITORIES: iProX

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