{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:12:49Z","timestamp":1790190769916,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cells (MSCs) are ubiquitous in the human body. Mesenchymal stem cells were initially isolated from bone marrow and later from other organs such as fatty tissues, umbilical cords, and gingiva. Their secretory capacities give them interesting immunomodulatory properties in cell therapy. Some studies have explored the use of MSCs to treat Sj\u00f6gren\u2019s syndrome (SS), a chronic inflammatory autoimmune disease that mainly affects exocrine glands, including salivary and lacrimal glands, although current treatments are only palliative. This systematic review summarizes the current data about the application of MSCs in SS. Reports show improvements in salivary secretions and a decrease in lymphocytic infiltration in salivary glands in patients and mice with SS after intravenous or infra-peritoneal injections of MSCs. MSC injections led to a decrease in inflammatory cytokines and an increase in anti-inflammatory cytokines. However, the intrinsic mechanism of action of these MSCs currently remains unknown.<\/jats:p>","DOI":"10.3390\/ijms221910474","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T21:38:09Z","timestamp":1632865089000},"page":"10474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Treatment of Sj\u00f6gren\u2019s Syndrome with Mesenchymal Stem Cells: A Systematic Review"],"prefix":"10.3390","volume":"22","author":[{"given":"Najwa","family":"Chihaby","sequence":"first","affiliation":[{"name":"UFR d\u2019Odontologie, University of Western Brittany, 29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4219-5219","authenticated-orcid":false,"given":"Marie","family":"Orliaguet","sequence":"additional","affiliation":[{"name":"UFR d\u2019Odontologie, University of Western Brittany, 29200 Brest, France"},{"name":"CHU de Brest, 29609 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00ebtitia","family":"Le Pottier","sequence":"additional","affiliation":[{"name":"UFR d\u2019Odontologie, University of Western Brittany, 29200 Brest, France"},{"name":"Inserm, LBAI, University of Western Brittany, UMR1227, 29609 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7287-5541","authenticated-orcid":false,"given":"Jacques-Olivier","family":"Pers","sequence":"additional","affiliation":[{"name":"UFR d\u2019Odontologie, University of Western Brittany, 29200 Brest, France"},{"name":"CHU de Brest, 29609 Brest, France"},{"name":"Inserm, LBAI, University of Western Brittany, UMR1227, 29609 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-4444","authenticated-orcid":false,"given":"Sylvie","family":"Boisram\u00e9","sequence":"additional","affiliation":[{"name":"UFR d\u2019Odontologie, University of Western Brittany, 29200 Brest, France"},{"name":"CHU de Brest, 29609 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jbspin.2015.02.015","article-title":"A prospective evaluation of dental and periodontal status in patients with suspected Sj\u00f6gren\u2019s syndrome","volume":"83","author":"Cornec","year":"2016","journal-title":"Jt. Bone Spine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.rdc.2018.03.002","article-title":"Update on Sj\u00f6gren Syndrome and Other Causes of Sicca in Older Adults","volume":"44","author":"Baer","year":"2018","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2310\/7750.2010.09033","article-title":"Dermatologic Manifestations of Sj\u00f6gren Syndrome","volume":"15","author":"Kittridge","year":"2011","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1093\/rheumatology\/key332","article-title":"B cells in Sj\u00f6gren\u2019s syndrome: From pathophysiology to therapeutic target","volume":"60","author":"Mielle","year":"2021","journal-title":"Rheumatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1365-2249.2012.04606.x","article-title":"Selective localization of T helper subsets in labial salivary glands from primary Sj\u00f6gren\u2019s syndrome patients","volume":"169","author":"Maehara","year":"2012","journal-title":"Clin. Exp. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s40744-020-00263-y","article-title":"Salivary Glands and Periodontal Changes in a Population of Sj\u00f6gren\u2019s and Sicca Syndrome Treated by Pilocarpine: A Pilot Study","volume":"8","author":"Depinoy","year":"2021","journal-title":"Rheumatol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4357865","DOI":"10.1155\/2018\/4357865","article-title":"Mesenchymal Stem Cells in Primary Sj\u00f6gren\u2019s Syndrome: Prospective and Challenges","volume":"2018","author":"Chen","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.oooo.2013.11.496","article-title":"Mesenchymal stem cell therapy for salivary gland dysfunction and xerostomia: A systematic review of preclinical studies","volume":"117","author":"Jensen","year":"2014","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Srivastava, A., and Makarenkova, H.P. (2020). Innate Immunity and Biological Therapies for the Treatment of Sj\u00f6gren\u2019s Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239172"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.3389\/fimmu.2018.02013","article-title":"Mesenchymal Stromal Cells Based Therapy in Systemic Sclerosis: Rational and Challenges","volume":"9","author":"Peltzer","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s12016-016-8552-9","article-title":"Adipose-Derived Mesenchymal Stem Cells in Autoimmune Disorders: State of the Art and Perspectives for Systemic Sclerosis","volume":"52","author":"Maria","year":"2017","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1089\/scd.2017.0161","article-title":"Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sj\u00f6gren\u2019s Syndrome","volume":"27","author":"Xu","year":"2018","journal-title":"Stem Cells Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9837035","DOI":"10.1155\/2018\/9837035","article-title":"Bone Morphogenetic Protein 6 Inhibits the Immunomodulatory Property of BMMSCs via Id1 in Sj\u00f6gren\u2019s Syndrome","volume":"2018","author":"Su","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Abughanam, G., Elkashty, O.A., Liu, Y., Bakkar, M.O., and Tran, S.D. (2021). Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren\u2019s Syndrome-Like Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020894"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1111\/odi.13113","article-title":"Stem cells from exfoliated deciduous teeth alleviate hyposalivation caused by Sj\u00f6gren syndrome","volume":"25","author":"Du","year":"2019","journal-title":"Oral Dis."},{"key":"ref_16","first-page":"954","article-title":"Murine embryonic mesenchymal stem cells attenuated xerostomia in Sj\u00f6gren-like mice via improving salivary gland epithelial cell structure and secretory function","volume":"13","author":"Gong","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2092315","DOI":"10.1155\/2018\/2092315","article-title":"Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sj\u00f6gren\u2019s Syndrome","volume":"2018","author":"Hai","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41419-020-2359-6","article-title":"Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sj\u00f6gren\u2019s syndrome","volume":"11","author":"Hu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Khalili, S., Liu, Y., Kornete, M., Roescher, N., Kodama, S., Peterson, A., Piccirillo, C.A., and Tran, S.D. (2012). Mesenchymal stromal cells improve salivary function and reduce lymphocytic infiltrates in mice with Sj\u00f6gren\u2019s-like disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038615"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/j.biocel.2010.08.008","article-title":"Bone marrow cells are a source of undifferentiated cells to prevent Sj\u00f6gren\u2019s syndrome and to preserve salivary glands function in the non-obese diabetic mice","volume":"42","author":"Khalili","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13287-021-02236-6","article-title":"Secreted factors from dental pulp stem cells improve Sj\u00f6gren\u2019s syndrome via regulatory T cell-mediated immunosuppression","volume":"12","author":"Ogata","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.reth.2021.01.006","article-title":"Dental pulp-derived stem cell-conditioned media attenuates secondary Sj\u00f6gren\u2019s syndrome via suppression of inflammatory cytokines in the submandibular glands","volume":"16","author":"Ogata","year":"2021","journal-title":"Regen. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1186\/s13287-020-01837-x","article-title":"Mesenchymal stem cells inhibited the differentiation of MDSCs via COX2\/PGE2 in experimental sialadenitis","volume":"11","author":"Qi","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.3892\/etm.2017.4313","article-title":"Effect of mesenchymal stem cells on Sj\u00f6gren-like mice and the microRNA expression profiles of splenic CD4+ T cells","volume":"13","author":"Ruan","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41423-020-00587-3","article-title":"Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sj\u00f6gren\u2019s syndrome by modulating the function of myeloid-derived suppressor cells","volume":"18","author":"Rui","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s13287-018-1023-x","article-title":"Mesenchymal stem cell transplantation ameliorates Sj\u00f6gren\u2019s syndrome via suppressing IL-12 production by dendritic cells","volume":"9","author":"Shi","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"604607","DOI":"10.3389\/fimmu.2020.604607","article-title":"Mesenchymal Stem Cell Enhances the Function of MDSCs in Experimental Sj\u00f6gren Syndrome","volume":"11","author":"Tian","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1182\/blood-2011-11-391144","article-title":"Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sj\u00f6gren syndrome","volume":"120","author":"Xu","year":"2012","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8253","DOI":"10.7150\/thno.37351","article-title":"Mesenchymal stem cell transplantation alleviates experimental Sj\u00f6gren\u2019s syndrome through IFN-\u03b2\/IL-27 signaling axis","volume":"9","author":"Yao","year":"2019","journal-title":"Theranostics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1080\/14397595.2019.1707996","article-title":"Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in Sj\u00f6gren\u2019s syndrome by inducing regulatory T cells","volume":"31","author":"Liu","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/rheumatology\/keu292","article-title":"In vitro immunomodulatory effects of microencapsulated umbilical cord Wharton jelly-derived mesenchymal stem cells in primary Sj\u00f6gren\u2019s syndrome","volume":"54","author":"Alunno","year":"2015","journal-title":"Rheumatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/rheumatology\/keu316","article-title":"Umbilical cord mesenchymal stem cells inhibit the differentiation of circulating T follicular helper cells in patients with primary Sj\u00f6gren\u2019s syndrome through the secretion of indoleamine 2,3-dioxygenase","volume":"54","author":"Liu","year":"2015","journal-title":"Rheumatology"},{"key":"ref_33","first-page":"43","article-title":"Mesenchymal stem cells negatively regulate CD4+ T cell activation in patients with primary Sj&ouml;gren syndrome through the miRNA-125b and miRNA-155 TCR pathway","volume":"23","author":"Gong","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/ar3348","article-title":"Disturbance of cytokine networks in Sj\u00f6gren\u2019s syndrome","volume":"13","author":"Youinou","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_35","first-page":"1131","article-title":"Interleukin-12 exacerbates Sj\u00f6gren\u2019s syndrome through induction of myeloid-derived suppressor cells","volume":"20","author":"Qi","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.0300-9475.2004.01432.x","article-title":"Circulating cytokines in primary Sj\u00f6gren\u2019s syndrome determined by a multiplex cytokine array system","volume":"59","author":"Szodoray","year":"2004","journal-title":"Scand. J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nm.3895","article-title":"IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases","volume":"21","author":"Teng","year":"2015","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e467","DOI":"10.1016\/j.lpm.2012.04.029","article-title":"Pathophysiological cytokine network in primary Sj\u00f6gren\u2019s syndrome","volume":"41","author":"Pers","year":"2012","journal-title":"Presse Medicale"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/art.39859","article-title":"2016 American College of Rheumatology\/European League Against Rheumatism Classification Criteria for Primary Sj\u00f6gren\u2019s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts","volume":"69","author":"Shiboski","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.biocel.2010.10.010","article-title":"Bone marrow-derived cells: A potential approach for the treatment of xerostomia","volume":"43","author":"Tran","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/s13287-018-1053-4","article-title":"Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: A long-term retrospective study","volume":"9","author":"Liang","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13287-019-1287-9","article-title":"The role of mesenchymal stem cells in hematopoietic stem cell transplantation: Prevention and treatment of graft-versus-host disease","volume":"10","author":"Zhao","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tessier, L., Bienzle, D., Williams, L.B., and Koch, T.G. (2015). Phenotypic and Immunomodulatory Properties of Equine Cord Blood-Derived Mesenchymal Stromal Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122954"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e232","DOI":"10.1038\/emm.2016.27","article-title":"Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease","volume":"48","author":"Son","year":"2016","journal-title":"Exp. Mol. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10474\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:06:31Z","timestamp":1760166391000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":44,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910474"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910474","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}