{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:07:19Z","timestamp":1781863639794,"version":"3.54.5"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008868","name":"Jiangsu Science and Technology Department","doi-asserted-by":"publisher","award":["JSYGY-2-2021-PJ133"],"award-info":[{"award-number":["JSYGY-2-2021-PJ133"]}],"id":[{"id":"10.13039\/501100008868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81110938"],"award-info":[{"award-number":["81110938"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this trial was to clinically assess the effect and safety of Adipose Tissue-derived Stem Cells\u00a0(ADSCs) treatment on primary Sjogren\u2019s Syndrome (pSS). In this 6-month randomized, triple-blind, placebo-controlled clinical trial, pSS patients were randomly assigned to two groups. After demographic characteristics and clinical examination were achieved, local injection of ADSCs into bilateral glands was performed with patients in ADSCs group (n\u2009=\u200935) and placebo solution was used for another group (n\u2009=\u200939) at three time points. Patients were followed up at 1-, 3- and 6-month. At each visit, studies of clinical and laboratory outcomes, as well as subjective symptoms, were conducted. A total of 74 subjects who met the including criteria were allocated in two groups and eventually 64 subjects (86.5%) completed the treatments and the follow-up assessments. Secretion of salivary and lachrymal glands were significantly improved in 3-month (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). A great improvement of European League Against Rheumatism Sj\u00f6gren\u2019s Syndrome Disease Activity Index (ESSDAI) was found after ADSCs treatment with intergroup comparison from baseline to follow-up (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). There is also a significant difference of European Alliance of Associations for Rheumatology SS Patient Reported Index (ESSPRI) between the two groups in the follow-up (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). A significant abatement of IgG, IgM, C3, C4 and ESR between two groups was observed in part of follow-up time points (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The ADSCs therapy can provide relief of oral and eye\u2019s dryness in our trial in a short time and has potential improvement of subjective and systemic syndromes of pSS.<\/jats:p>","DOI":"10.1038\/s41598-023-40802-5","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T09:10:32Z","timestamp":1692436232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of adipose tissue-derived stem cells therapy on clinical response in patients with primary Sjogren\u2019s syndrome"],"prefix":"10.1038","volume":"13","author":[{"given":"Fangfang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongya","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"40802_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1177\/0961203318801673","volume":"27","author":"SJ Bowman","year":"2018","unstructured":"Bowman, S. J. Primary Sj\u00f6gren\u2019s syndrome. Lupus 27, 32\u201335 (2018).","journal-title":"Lupus"},{"key":"40802_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.938837","volume":"13","author":"H Luo","year":"2022","unstructured":"Luo, H. & Zhou, X. Bioinformatics analysis of potential common pathogenic mechanisms for Covid-19 infection and primary Sjogren\u2019s syndrome. Front. Immunol. 13, 938837 (2022).","journal-title":"Front. Immunol."},{"key":"40802_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/annrheumdis-2019-216114","volume":"79","author":"M Ramos-casals","year":"2019","unstructured":"Ramos-casals, M. et al. Eular recommendations for the management of Sj\u00f6gren\u2019s syndrome with topical and systemic therapies. Ann. Rheum. Dis. 79, 3\u201318 (2019).","journal-title":"Ann. Rheum. Dis."},{"key":"40802_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2022.152062","volume":"56","author":"B Ming","year":"2022","unstructured":"Ming, B. et al. Immunopathogenesis of Sjogren\u2019s syndrome: Current state of damps. Semin. Arthritis. Rheum. 56, 152062 (2022).","journal-title":"Semin. Arthritis. Rheum."},{"key":"40802_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2022.105406","volume":"89","author":"J Ritter","year":"2022","unstructured":"Ritter, J. et al. Current and future treatment in primary Sj\u00f6gren\u2019s syndrome\u2013a still challenging development. Joint Bone Spine 89, 105406 (2022).","journal-title":"Joint Bone Spine"},{"key":"40802_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.684999","volume":"12","author":"W Du","year":"2021","unstructured":"Du, W. et al. The multiple roles of B cells in the pathogenesis of Sj\u00f6gren\u2019s syndrome. Front. Immunol. 12, 684999 (2021).","journal-title":"Front. Immunol."},{"key":"40802_CR7","doi-asserted-by":"publisher","first-page":"707104","DOI":"10.3389\/fmed.2021.707104","volume":"8","author":"F Chowdhury","year":"2021","unstructured":"Chowdhury, F., Tappuni, A. & Bombardieri, M. Biological therapy in primary Sj\u00f6gren\u2019s syndrome: Effect on salivary gland function and inflammation. Front. Med. (lausanne) 8, 707104 (2021).","journal-title":"Front. Med. (lausanne)"},{"key":"40802_CR8","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/978-1-4939-7799-4_9","volume":"1","author":"P Gentile","year":"2018","unstructured":"Gentile, P. & Cervelli, V. Adipose-derived stromal vascular fraction cells and platelet-rich plasma: Basic and clinical implications for tissue engineering therapies in regenerative surgery. Methods. Mol. Biol. 1, 107\u2013122 (2018).","journal-title":"Methods. Mol. Biol."},{"key":"40802_CR9","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.reth.2020.08.004","volume":"15","author":"K Tsujimaru","year":"2020","unstructured":"Tsujimaru, K. et al. Extracellular microvesicles that originated adipose tissue derived mesenchymal stem cells have the potential ability to improve rheumatoid arthritis on mice. Regen. Ther. 15, 305\u2013311 (2020).","journal-title":"Regen. Ther."},{"key":"40802_CR10","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.jos.2021.12.020","volume":"28","author":"A Kuwasawa","year":"2022","unstructured":"Kuwasawa, A. et al. Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume. J. Orthop. Sci. 28, 408\u2013415 (2022).","journal-title":"J. Orthop. Sci."},{"key":"40802_CR11","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1089\/scd.2017.0071","volume":"26","author":"MP Marquez","year":"2017","unstructured":"Marquez, M. P. et al. The role of cellular proliferation in adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells. Stem. Cells. Dev. 26, 1578\u20131595 (2017).","journal-title":"Stem. Cells. Dev."},{"key":"40802_CR12","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1002\/acr.21591","volume":"64","author":"SC Shiboski","year":"2012","unstructured":"Shiboski, S. C. et al. American college of rheumatology classification criteria for Sj\u00f6gren\u2019s syndrome: A data-driven, expert consensus approach in the Sj\u00f6gren\u2019s international collaborative clinical alliance cohort. Arthritis. Care. Res. (Hoboken) 64, 87\u2013475 (2012).","journal-title":"Arthritis. Care. Res. (Hoboken)"},{"key":"40802_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.749481","volume":"12","author":"E Kuca-warnawin","year":"2022","unstructured":"Kuca-warnawin, E. et al. Impact and possible mechanism(s) of adipose tissue-derived mesenchymal stem cells on T-cell proliferation in patients with rheumatic disease. Front. Physiol. 12, 749481 (2022).","journal-title":"Front. Physiol."},{"key":"40802_CR14","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1001\/jamanetworkopen.2022.41451","volume":"5","author":"J He","year":"2022","unstructured":"He, J. et al. Efficacy and safety of low-dose interleukin 2 for primary Sj\u00f6gren syndrome: A randomized clinical trial. Jama. Netw. Open. 5, 26 (2022).","journal-title":"Jama. Netw. Open."},{"key":"40802_CR15","doi-asserted-by":"publisher","first-page":"4107","DOI":"10.1007\/s00784-020-03741-3","volume":"25","author":"D Wr\u00f3bel-dudzi\u0144ska","year":"2021","unstructured":"Wr\u00f3bel-dudzi\u0144ska, D. et al. The use of schirmer strips to measure salivary and lacrimal flow in non-sj\u00f6gren patients. Clin. Oral. Investig. 25, 4107\u20134114 (2021).","journal-title":"Clin. Oral. Investig."},{"key":"40802_CR16","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s40744-022-00487-0","volume":"9","author":"C Cooper","year":"2022","unstructured":"Cooper, C. et al. Qualitative research with patients and physicians to assess content validity and meaningful change on ESSDAI and ESSPRI in Sj\u00f6gren\u2019s. Rheumatol. Ther. 9, 16 (2022).","journal-title":"Rheumatol. Ther."},{"key":"40802_CR17","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1007\/s00393-018-0450-5","volume":"78","author":"W Zhang","year":"2019","unstructured":"Zhang, W. et al. Transplantation of adipose tissue-derived stem cells ameliorates autoimmune pathogenesis in Mrl\/lpr Mice\u202f: Modulation of the balance between Th17 and Treg. Z. Rheumatol. 78, 82\u201388 (2019).","journal-title":"Z. Rheumatol."},{"key":"40802_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109152","volume":"111","author":"T Sun","year":"2022","unstructured":"Sun, T. et al. Mesenchymal stem cell transplantation alleviates Sj\u00f6gren\u2019s syndrome symptoms by modulating Tim-3 expression. Int. Immunopharmacol. 111, 109152 (2022).","journal-title":"Int. Immunopharmacol."},{"key":"40802_CR19","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1111\/1756-185X.13839","volume":"23","author":"J Wang","year":"2020","unstructured":"Wang, J., Zhou, L. & Liu, B. Update on disease pathogenesis, diagnosis, and management of primary Sj\u00f6gren\u2019s syndrome. Int. J. Rheum. Dis. 23, 723\u2013727 (2020).","journal-title":"Int. J. Rheum. Dis."},{"key":"40802_CR20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12916-017-0837-1","volume":"15","author":"F Franceschini","year":"2017","unstructured":"Franceschini, F. et al. The 2016 classification criteria for primary Sjogren\u2019s syndrome: What\u2019s new?. Bmc. Med. 15, 69 (2017).","journal-title":"Bmc. Med."},{"key":"40802_CR21","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jaut.2013.12.010","volume":"51","author":"R Seror","year":"2014","unstructured":"Seror, R. et al. Outcome measures for primary Sj\u00f6gren\u2019s syndrome: A comprehensive review. J. Autoimmun. 51, 6\u201351 (2014).","journal-title":"J. Autoimmun."},{"key":"40802_CR22","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1097\/BOR.0000000000000473","volume":"30","author":"E Pontarini","year":"2018","unstructured":"Pontarini, E., Lucchesi, D. & Bombardieri, M. Current views on the pathogenesis of Sj\u00f6gren\u2019s syndrome. Curr. Opin. Rheumatol. 30, 215\u2013221 (2018).","journal-title":"Curr. Opin. Rheumatol."},{"key":"40802_CR23","doi-asserted-by":"crossref","unstructured":"Kelly, A. L. et al. Sj\u00f6gren syndrome: New insights in the pathogenesis and role of nuclear medicine.[Z], (2022).","DOI":"10.3390\/jcm11175227"},{"key":"40802_CR24","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1007\/s00784-022-04576-w","volume":"26","author":"Z Assy","year":"2022","unstructured":"Assy, Z. et al. Preferences of Sj\u00f6gren\u2019s syndrome patients regarding potential new saliva substitutes. Clin. Oral. Investig. 26, 6245\u20136252 (2022).","journal-title":"Clin. Oral. Investig."},{"key":"40802_CR25","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1136\/rmdopen-2019-001064","volume":"5","author":"P Brito-zer\u00f3n","year":"2019","unstructured":"Brito-zer\u00f3n, P. et al. Efficacy and safety of topical and systemic medications: A systematic literature review informing the eular recommendations for the management of Sj\u00f6gren\u2019s syndrome. RMD Open 5, 26 (2019).","journal-title":"RMD Open"},{"key":"40802_CR26","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1111\/bjd.16442","volume":"30","author":"M Cifuentes","year":"2018","unstructured":"Cifuentes, M., Barrio-d\u00edaz, P. D. & Vera-kellet, C. Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sj\u00f6gren syndrome: a double-blind randomized controlled trial. Br. J. Dermatol. 30, 1056\u20131061 (2018).","journal-title":"Br. J. Dermatol."},{"key":"40802_CR27","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3892\/etm.2022.11524","volume":"24","author":"Z Li","year":"2022","unstructured":"Li, Z. et al. Adipose-derived stem cells postpone the progression of Sj\u00f6gren\u2019s syndrome by upregulating the hippo signaling pathway. Exp. Ther. Med. 24, 587 (2022).","journal-title":"Exp. Ther. Med."},{"key":"40802_CR28","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.jcyt.2020.09.008","volume":"23","author":"SS Mccoy","year":"2020","unstructured":"Mccoy, S. S. et al. Minor salivary gland mesenchymal stromal cells derived from patients with Sj\u04e7gren\u2019s syndrome deploy intact immune plasticity. Cytotherapy 23, 301\u2013310 (2020).","journal-title":"Cytotherapy"},{"key":"40802_CR29","first-page":"213","volume":"10","author":"J Freitag","year":"2018","unstructured":"Freitag, J. et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Am. J. Transl. Res. 10, 213\u2013230 (2018).","journal-title":"Am. J. Transl. Res."},{"key":"40802_CR30","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12967-018-1591-7","volume":"1","author":"JM Lamo-espinosa","year":"2018","unstructured":"Lamo-espinosa, J. M. et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: Long-term follow up of a multicenter randomized controlled clinical trial (phase I\/ii). J. Transl. Med. 1, 213 (2018).","journal-title":"J. Transl. Med."},{"key":"40802_CR31","first-page":"15","volume":"12","author":"S Summer","year":"2022","unstructured":"Summer, S. et al. Mesenchymal stem cells support human vascular endothelial cells to form vascular sprouts in human platelet lysate-based matrices. PLoS ONE 12, 15 (2022).","journal-title":"PLoS ONE"},{"key":"40802_CR32","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.clim.2019.04.009","volume":"203","author":"FB Vivino","year":"2019","unstructured":"Vivino, F. B. et al. Sjogren\u2019s syndrome: An update on disease pathogenesis. Clin. Manif. Treatment. Clin. Immunol. 203, 81\u2013121 (2019).","journal-title":"Clin. Manif. Treatment. Clin. Immunol."},{"key":"40802_CR33","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.autrev.2018.05.005","volume":"17","author":"K Psianou","year":"2018","unstructured":"Psianou, K. et al. Clinical and Immunological Parameters of Sj\u00f6gren\u2019s syndrome. Autoimmun. Rev. 17, 1053\u20131064 (2018).","journal-title":"Autoimmun. Rev."},{"key":"40802_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2022.101586","volume":"72","author":"WA Alasmari","year":"2022","unstructured":"Alasmari, W. A. et al. Adipose-derived stem cell and their extracellular vesicles ameliorates immune function, and cardiac markers in experimental model of cardiorenal syndrome type Iii: Tnf-\u03b1, Ifn-\u03b3 and Il-10 cytokine production and their correlation with genotype. Transpl. Immunol. 72, 101586 (2022).","journal-title":"Transpl. Immunol."},{"key":"40802_CR35","first-page":"744194","volume":"28","author":"H Chen","year":"2021","unstructured":"Chen, H., Lai, J. & Yu, M. Traditional Chinese medicine in patients with primary Sjogren\u2019s syndrome: A randomized, double-blind. Placebo-Controlled Clin. Trial. Front. Med. (lausanne) 28, 744194 (2021).","journal-title":"Placebo-Controlled Clin. Trial. Front. Med. (lausanne)"},{"key":"40802_CR36","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1136\/annrheumdis-2017-212672","volume":"7","author":"KH Karagozoglu","year":"2018","unstructured":"Karagozoglu, K. H. et al. Sialendoscopy enhances salivary gland function in Sj\u00f6gren\u2019s syndrome: A 6-month follow-up, randomised and controlled. Single Blind Study. Ann. Rheum Dis. 7, 1025\u20131031 (2018).","journal-title":"Single Blind Study. Ann. Rheum Dis."},{"key":"40802_CR37","doi-asserted-by":"publisher","first-page":"100","DOI":"10.55563\/clinexprheumatol\/i8g5nd","volume":"39","author":"LD Wolff","year":"2021","unstructured":"Wolff, L. D. et al. Development and performance of the clinical trials essdai (clintrialsessdai), consisting of frequently active clinical domains, in two randomised controlled trials in primary Sj\u00f6gren\u2019s syndrome. Clin. Exp. Rheumatol. 39, 100\u2013106 (2021).","journal-title":"Clin. Exp. Rheumatol."},{"key":"40802_CR38","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s42358-022-00267-y","volume":"62","author":"VFM Trevisani","year":"2022","unstructured":"Trevisani, V. F. M. et al. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sj\u00f6gren syndrome: Results of an epidemiologic systematic review\/meta-analysis and a consensus guideline From the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic). Adv. Rheumatol. 62, 35 (2022).","journal-title":"Adv. Rheumatol."},{"key":"40802_CR39","first-page":"1053","volume":"10","author":"C Chang","year":"2018","unstructured":"Chang, C. et al. Adipose-derived mesenchymal stem cell-derived exosomes alleviate overwhelming systemic inflammatory reaction and organ damage and improve outcome in rat sepsis syndrome. Am. J. Transl. Res. 10, 1053\u20131070 (2018).","journal-title":"Am. J. Transl. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-40802-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-40802-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-40802-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T17:16:02Z","timestamp":1700241362000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-40802-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,19]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["40802"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-40802-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,19]]},"assertion":[{"value":"11 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13521"}}