Establishment of human minor salivary gland organoids in laminin-GelMA hydrogel from healthy individuals and Sjögren’s disease patients

Abstract

Biopsies of human minor salivary glands (hMSGs), located beneath the oral mucosa, are crucial for a definitive clinical diagnosis of Sjögren’s Disease (SjD)。Although organoids from various exocrine glands have been cultured, organoids comprising the diverse cell types of hMSGs have not yet been successful. In this study, we established long-term cultures of hMSGs organoids derived from both healthy individuals and patients with SjD. The organoids, cultured in artificial laminin-GelMA hydrogel, retain distinct phenotypic and functional characteristics of the native glands, both when stimulated with neurotransmitters in vitro and upon transplantation in vivo. Single-cell RNA sequencing revealed that organoids from healthy individuals and from SjD patients exhibit unique phenotypic differences. Furthermore, treatment with tofacitinib enhanced the proliferation of patient organoids by inhibiting the JAK-STAT pathway, suggesting a potential therapeutic strategy for further investigation. Here, we derived organoids from healthy individuals as potential transplant material in regeneration medicine, and developed SjD hMSG organoids for use as a disease model for exploring SjD pathogenesis and developing therapeutic strategies.