TY - JOUR
T1 - Development of salivary gland organoids derived from patient biopsies
T2 - a functional model of Sjögren's disease
AU - Meudec, Loïc
AU - Goudarzi, Negaar
AU - Silva-Saffar, Sacha E.
AU - Pascaud, Juliette
AU - Jaulin, Fanny
AU - Pascal, Quentin
AU - Lazure, Thierry
AU - Bechara, Rami
AU - Mariette, Xavier
AU - Nocturne, Gaetane
N1 - Publisher Copyright:
© 2025 European Alliance of Associations for Rheumatology (EULAR)
PY - 2025/7/1
Y1 - 2025/7/1
N2 - Objectives: Salivary gland epithelial cells (SGECs) play a key role in Sjögren's disease (SjD) as an active contributor to the pathogenesis. Current models lack clear epithelial readouts. Our aim was to establish a more advanced model by developing salivary gland organoids (SGOs) from labial salivary gland biopsies (LSGBs) of SjD patients and sicca controls. Methods: We included SjD patients fulfilling the American College of Rheumatology/European League Against Rheumatism 2016 criteria and sicca controls. LSGBs were dissociated, encapsulated in extracellular matrix, and submerged in growth expansion medium for long-term culture. SGOs were primarily cultured in differentiation medium and then transferred to a low attachment plate to form differentiated SGOs (DIF-SGOs). Results: We included 13 SjD and 15 controls. In both groups, SGOs were formed, demonstrating long-term culture viability and comparable self-renewal capacity (3.3 ± 1.7 months). DIF-SGOs comparably exhibited mature acinar (aquaporin 5, amylase), ductal (cytokeratins 5 and 7) and myoepithelial (α-smooth muscle actin) markers in both groups. DIF-SGOs were responsive to inflammation by expressing BAFF, CXCL10 and IL7 upon stimulation with poly(I:C) and interferon-α. DIF-SGOs also demonstrated a swelling response to cholinergic stimulation by pilocarpine. We observed significant differences between SjD- and control-derived SGOs. Notably, SjD-derived DIF-SGOs consistently maintained a persistent interferon signature throughout long-term culture. In addition, the swelling capacity was reduced in SjD-derived DIF-SGOs compared to control. However, treatment with tofacitinib enhanced the swelling ability, suggesting a potential effect on saliva production. Conclusions: We successfully developed SGOs from LSGBs of SjD patients, allowing long-term culture and faithfully recapitulating the disease phenotype. This model holds promise as a valuable tool for drug screening.
AB - Objectives: Salivary gland epithelial cells (SGECs) play a key role in Sjögren's disease (SjD) as an active contributor to the pathogenesis. Current models lack clear epithelial readouts. Our aim was to establish a more advanced model by developing salivary gland organoids (SGOs) from labial salivary gland biopsies (LSGBs) of SjD patients and sicca controls. Methods: We included SjD patients fulfilling the American College of Rheumatology/European League Against Rheumatism 2016 criteria and sicca controls. LSGBs were dissociated, encapsulated in extracellular matrix, and submerged in growth expansion medium for long-term culture. SGOs were primarily cultured in differentiation medium and then transferred to a low attachment plate to form differentiated SGOs (DIF-SGOs). Results: We included 13 SjD and 15 controls. In both groups, SGOs were formed, demonstrating long-term culture viability and comparable self-renewal capacity (3.3 ± 1.7 months). DIF-SGOs comparably exhibited mature acinar (aquaporin 5, amylase), ductal (cytokeratins 5 and 7) and myoepithelial (α-smooth muscle actin) markers in both groups. DIF-SGOs were responsive to inflammation by expressing BAFF, CXCL10 and IL7 upon stimulation with poly(I:C) and interferon-α. DIF-SGOs also demonstrated a swelling response to cholinergic stimulation by pilocarpine. We observed significant differences between SjD- and control-derived SGOs. Notably, SjD-derived DIF-SGOs consistently maintained a persistent interferon signature throughout long-term culture. In addition, the swelling capacity was reduced in SjD-derived DIF-SGOs compared to control. However, treatment with tofacitinib enhanced the swelling ability, suggesting a potential effect on saliva production. Conclusions: We successfully developed SGOs from LSGBs of SjD patients, allowing long-term culture and faithfully recapitulating the disease phenotype. This model holds promise as a valuable tool for drug screening.
UR - http://www.scopus.com/inward/record.url?scp=105005491299&partnerID=8YFLogxK
U2 - 10.1016/j.ard.2025.04.020
DO - 10.1016/j.ard.2025.04.020
M3 - Article
AN - SCOPUS:105005491299
SN - 0003-4967
VL - 84
SP - 1195
EP - 1206
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 7
ER -