ArticleArthritis & rheumatology (Hoboken, N.J.)2019
Salivary Gland Stem Cells Age Prematurely in Primary Sjögren's Syndrome.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Pooled it
- Composition and regulation of the immune microenvironment of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2022Pooled it
- Sjögren's disease patients with no hyposalivation and with short oral dryness complaints contain more T cells in salivary gland parenchyma.Rheumatology (Oxford, England) · 2026Article
- Molecular classification of primary Sjögren's syndrome based on salivary gland omics.Arthritis research & therapy · 2026Article
- An integrated single-cell and spatial proteotranscriptomics atlas of fibroblast-driven immunoregulation within the human adult oral cavity.Cell press blue · 2026Article
- IL-4 triggers salivary duct dilatation via SHH signaling and exacerbates Sjögren's disease.Cell reports · 2026Article
- Update on the Aetiopathogenesis of Sjögren Disease: From Interferon Signaling to Epithelial Dysfunction.Journal of clinical medicine · 2026Review
- The Role of Cellular Senescence in Oral Health and Disease.International journal of molecular sciences · 2026Review
- GZMK⁺CD8⁺ T Cells Induce Acinar Cell Senescence and Salivary Secretion Impairment in Sjögren's Syndrome via Mitochondrial Dysfunction and TMEM16A Chloride Channel Disruption.International journal of biological sciences · 2026Article
- Telomere length in leukocyte as biomarker for diagnosis of primary Sjögren's syndrome: a cross-sectional study.Clinical rheumatology · 2026Article
- IFNγ and TNFα optimize salivary gland mesenchymal stromal cells: an alternative to marrow- and adipose-MSCs for radiation xerostomia.Regenerative therapy · 2025Article
- Organoid-based modeling and regenerative strategies for salivary gland dysfunction.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Salivary gland cell senescence in Sjögren's syndrome: current research and novel therapeutic directions.Immunity & ageing : I & A · 2025Review
- Extracellular vesicles derived from salivary gland stem cells cultured on microwell scaffolds loaded with WNT3A promote the recovery of salivary gland function damaged by radiation via the YWHAZ-PI3K-AKT pathway.Bioactive materials · 2025Article
- Chemical reprogramming culture for the expansion of salivary gland epithelial basal progenitor cells.Stem cell research & therapy · 2025Article
- Age-Related Oral and Para-Oral Tissue Disorders: The Evolving Therapeutic and Diagnostic Potential of Exosomes.Dentistry journal · 2025Review
- Common pathological mechanisms and therapeutic strategies in primary Sjogren's syndrome and primary biliary cholangitis: from tissue immune microenvironment to targeted therapy.Frontiers in immunology · 2025Review
- Connecting the Dots: Telomere Shortening and Rheumatic Diseases.Biomolecules · 2024Review
- The impact of alternate-day fasting on the salivary gland stem cell compartments in non-obese diabetic mice with newly established Sjögren's syndrome.Biochimica et biophysica acta. Molecular cell research · 2024Article
- Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells.European journal of medical research · 2024Review
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Authors and funding
14 authors at 6 institutions in 6 countries.
Funding
Abstract
objectiveA major characteristic of the autoimmune disease primary Sjögren's syndrome (SS) is salivary gland (SG) hypofunction. The inability of resident SG stem cells (SGSCs) to maintain homeostasis and saliva production has never been explained and limits our comprehension of mechanisms underlying primary SS. The present study was undertaken to investigate the role of salivary gland stem cells in hyposalivation in primary SS.
methodsSGSCs were isolated from parotid biopsy samples from controls and patients classified as having primary SS or incomplete primary SS, according to the American College of Rheumatology/European League Against Rheumatism criteria. Self-renewal and differentiation assays were used to determine SGSC regenerative potential, RNA was extracted for sequencing analysis, single telomere length analysis was conducted to determine telomere length, and frozen tissue samples were used for immunohistochemical analysis.
resultsSGSCs isolated from primary SS parotid gland biopsy samples were regeneratively inferior to healthy control specimens. We demonstrated that SGSCs from samples from patients with primary SS are not only lower in number and less able to differentiate, but are likely to be senescent, as revealed by telomere length analysis, RNA sequencing, and immunostaining. We further found that SGSCs exposed to primary SS-associated proinflammatory cytokines we induced to proliferate, express senescence-associated genes, and subsequently differentiate into intercalated duct cells. We also localized p16+ senescent cells to the intercalated ducts in primary SS SG tissue, suggesting a block in SGSC differentiation into acinar cells.
conclusionThis study represents the first characterization of SGSCs in primary SS, and also the first demonstration of a linkage between an autoimmune disease and a parenchymal premature-aging phenotype. The knowledge garnered in this study indicates that disease-modifying antirheumatic drugs used to treat primary SS are not likely to restore saliva production, and should be supplemented with fresh SGSCs to recover saliva production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.