{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:22:47Z","timestamp":1792664567623,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kangstem Biotech"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background\/purpose<\/jats:title>\n                    <jats:p>Mesenchymal stem cell (MSC) therapy offers promise for treating autoimmune diseases due to its strong immunomodulatory effects. We investigated the long-term safety of a single intravenous injection with human umbilical cord blood-derived (hUCB)-MSCs in patients with rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with RA who met the 2010 ACR\/EULAR classification criteria and received a single intravenous infusion of hUCB-MSCs (2.5\u2009\u00d7\u2009107, 5.0\u2009\u00d7\u2009107, 1.0\u2009\u00d7\u2009108 cells) in a phase I trial (NCT02221258) entered this 5-year observational pilot study. Safety assessments were performed at 3, 6, and 12 months after infusion and annually thereafter. Safety endpoints included overall adverse events (AEs), serious adverse events (SAEs), and AEs of special interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine patients were treated. The most common AEs were osteoarthritis (44.4%) and nasopharyngitis (44.4%). SAEs occurred in 5 patients (55.6%); a serious infection (cellulitis) occurred in 1 patient in the 1.0\u2009\u00d7\u2009108 group and resolved after treatment. Benign ovarian and breast tumors were reported in 2 patients 3 years post-infusion. No deaths, thromboembolism, or malignancies occurred during the follow-up period. Laboratory findings remained stable except for 1 case each of transient hypertriglyceridemia and mild eosinophilia. While DAS28 improved markedly by 3-6 months, disease activity gradually increased over 5 years, suggesting waning efficacy after a single infusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The long-term safety profile of a single dose of intravenous hUCB-MSC in patients with RA appears acceptable; however, repeated-dose regimens may be needed for sustained disease control and further safety evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szag062","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:47:12Z","timestamp":1781783232000},"source":"Crossref","is-referenced-by-count":1,"title":["Long-term safety of intravenous human umbilical cord blood-derived mesenchymal stem cell therapy in rheumatoid arthritis: a 5-year follow-up study"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6813-4182","authenticated-orcid":false,"given":"Eun Hye","family":"Park","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Chung-Ang University College of Medicine , Seoul \u00a006974,","place":["Republic of Korea"]},{"name":"Department of Internal Medicine, Division of Rheumatology, Chung-Ang University Gwangmyeong Hospital , Gwangmyeong 14353,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Seoul Metropolitan Government\u2013Seoul National University Boramae Medical Center , Seoul 07061,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Sun","family":"Kang","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Regenerative Medicine, Kangstem Biotech , Seoul 06181,","place":["Republic of Korea"]},{"name":"Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University , Seoul 08826,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-7598","authenticated-orcid":false,"given":"Kichul","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Seoul Metropolitan Government\u2013Seoul National University Boramae Medical Center , Seoul 07061,","place":["Republic of Korea"]},{"name":"Department of Internal Medicine, College of Medicine, Seoul National University , Seoul 03080,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026080517163736200_szag062-B1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"2026080517163736200_szag062-B2","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1002\/acr.23551","article-title":"Ultrasonographic efficacy of biologic and targeted synthetic disease-modifying antirheumatic drug therapy in rheumatoid arthritis from a multicenter rheumatoid arthritis ultrasound prospective cohort in Japan","volume":"70","author":"Nishino","year":"2018","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2026080517163736200_szag062-B3","doi-asserted-by":"publisher","first-page":"v51","DOI":"10.1093\/rheumatology\/kez389","article-title":"Effect of biologics and targeted synthetic disease-modifying anti-rheumatic drugs on fatigue in rheumatoid arthritis","volume":"58","author":"Choy","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"2026080517163736200_szag062-B4","doi-asserted-by":"publisher","first-page":"ii37","DOI":"10.1136\/ard.62.suppl_2.ii37","article-title":"Role of tumour necrosis factor (TNF) in host defence against tuberculosis: implications for immunotherapies targeting TNF","volume":"62 Suppl 2","author":"Ehlers","year":"2003","journal-title":"Ann Rheum Dis"},{"key":"2026080517163736200_szag062-B5","doi-asserted-by":"publisher","first-page":"7140","DOI":"10.1038\/s41598-022-10777-w","article-title":"Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database","volume":"12","author":"Hoisnard","year":"2022","journal-title":"Sci Rep"},{"key":"2026080517163736200_szag062-B6","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1002\/art.21137","article-title":"Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden","volume":"52","author":"Askling","year":"2005","journal-title":"Arthritis Rheum"},{"key":"2026080517163736200_szag062-B7","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.4254\/wjh.v7.i21.2344","article-title":"Hepatitis B virus reactivation with a rituximab-containing regimen","volume":"7","author":"Tsutsumi","year":"2015","journal-title":"World J Hepatol"},{"key":"2026080517163736200_szag062-B8","doi-asserted-by":"publisher","first-page":"1241954","DOI":"10.3389\/fphar.2023.1241954","article-title":"Risk of herpes zoster associated with JAK inhibitors in immune-mediated inflammatory diseases: a systematic review and network meta-analysis","volume":"14","author":"Xu","year":"2023","journal-title":"Front Pharmacol"},{"key":"2026080517163736200_szag062-B9","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1136\/ard-2023-224049","article-title":"JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications","volume":"82","author":"Russell","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"2026080517163736200_szag062-B10","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s10067-019-04865-y","article-title":"Risk of non-melanoma skin cancer for rheumatoid arthritis patients receiving TNF antagonist: a systematic review and meta-analysis","volume":"39","author":"Wang","year":"2020","journal-title":"Clin Rheumatol"},{"key":"2026080517163736200_szag062-B11","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1097\/BOR.0000000000000370","article-title":"Mesenchymal stem cells for the management of rheumatoid arthritis: immune modulation, repair or both?","volume":"29","author":"Ansboro","year":"2017","journal-title":"Curr Opin Rheumatol"},{"key":"2026080517163736200_szag062-B12","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.ebiom.2019.08.073","article-title":"Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis","volume":"47","author":"Liu","year":"2019","journal-title":"EBioMedicine"},{"key":"2026080517163736200_szag062-B13","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1136\/annrheumdis-2015-208918","article-title":"Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib\/IIa clinical trial","volume":"76","author":"Alvaro-Gracia","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2026080517163736200_szag062-B14","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1016\/j.biopha.2018.11.056","article-title":"Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: a successful clinical trial in Iran","volume":"109","author":"Ghoryani","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"2026080517163736200_szag062-B15","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1002\/sctm.18-0031","article-title":"Intravenous infusion of umbilical cord blood-derived mesenchymal stem cells in rheumatoid arthritis: a phase IA clinical trial","volume":"7","author":"Park","year":"2018","journal-title":"Stem Cells Transl Med"},{"key":"2026080517163736200_szag062-B16","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1089\/scd.2013.0023","article-title":"Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy","volume":"22","author":"Wang","year":"2013","journal-title":"Stem Cells Dev"},{"key":"2026080517163736200_szag062-B17","doi-asserted-by":"publisher","first-page":"8864572","DOI":"10.1155\/2020\/8864572","article-title":"Dental tissue-derived human mesenchymal stem cells and their potential in therapeutic application","volume":"2020","author":"Gan","year":"2020","journal-title":"Stem Cells Int"},{"key":"2026080517163736200_szag062-B18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/7651_2018_199","article-title":"Human synovium-derived mesenchymal stem cells: ex vivo analysis","volume":"2045","author":"Zupan","year":"2019","journal-title":"Methods Mol Biol"},{"key":"2026080517163736200_szag062-B19","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1002\/art.21753","article-title":"Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis","volume":"54","author":"De Bari","year":"2006","journal-title":"Arthritis Rheum"},{"key":"2026080517163736200_szag062-B20","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1634\/stemcells.2005-0342","article-title":"Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue","volume":"24","author":"Kern","year":"2006","journal-title":"Stem Cells (1981)"},{"key":"2026080517163736200_szag062-B21","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1634\/stemcells.2006-0709","article-title":"Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow","volume":"25","author":"Baksh","year":"2007","journal-title":"Stem Cells (1981)"},{"key":"2026080517163736200_szag062-B22","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1136\/ard.2010.138461","article-title":"2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism Collaborative Initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"2026080517163736200_szag062-B23","author":"Administration USFaD","year":"2025"},{"key":"2026080517163736200_szag062-B24","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1136\/annrheumdis-2015-207841","article-title":"Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance","volume":"74","author":"Winthrop","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"2026080517163736200_szag062-B25","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N Engl J Med"},{"key":"2026080517163736200_szag062-B26","doi-asserted-by":"publisher","first-page":"103427","DOI":"10.1016\/j.ebiom.2021.103427","article-title":"Mesenchymal stem\/stromal cell-based therapy for the treatment of rheumatoid arthritis: an update on preclinical studies","volume":"69","author":"Lopez-Santalla","year":"2021","journal-title":"EBioMedicine"},{"key":"2026080517163736200_szag062-B27","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.stem.2013.09.006","article-title":"Mesenchymal stromal cells: sensors and switchers of inflammation","volume":"13","author":"Bernardo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2026080517163736200_szag062-B28","doi-asserted-by":"publisher","first-page":"5136","DOI":"10.4049\/jimmunol.1500332","article-title":"Adipose-derived mesenchymal stem cells prevent systemic bone loss in collagen-induced arthritis","volume":"195","author":"Garimella","year":"2015","journal-title":"J Immunol"},{"key":"2026080517163736200_szag062-B29","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3389\/fimmu.2012.00212","article-title":"Immunomodulatory effect of mesenchymal stem cells on B cells","volume":"3","author":"Franquesa","year":"2012","journal-title":"Front Immunol"},{"key":"2026080517163736200_szag062-B30","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1002\/art.22511","article-title":"Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis","volume":"56","author":"Augello","year":"2007","journal-title":"Arthritis Rheum"},{"key":"2026080517163736200_szag062-B31","doi-asserted-by":"publisher","first-page":"574","DOI":"10.2174\/156652412800619950","article-title":"Immunosuppressive properties of mesenchymal stem cells: advances and applications","volume":"12","author":"De Miguel","year":"2012","journal-title":"Curr Mol Med"},{"key":"2026080517163736200_szag062-B32","doi-asserted-by":"publisher","first-page":"e13267","DOI":"10.1111\/sji.13267","article-title":"Immunogenicity of mesenchymal stromal\/stem cells","volume":"97","author":"Chen","year":"2023","journal-title":"Scand J Immunol"},{"key":"2026080517163736200_szag062-B33","doi-asserted-by":"publisher","first-page":"4331","DOI":"10.2147\/DDDT.S225613","article-title":"Efficacy and safety of umbilical cord mesenchymal stem cell therapy for rheumatoid arthritis patients: a prospective phase I\/II study","volume":"13","author":"Wang","year":"2019","journal-title":"Drug Des Devel Ther"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/8\/szag062\/70500204\/szag062.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/8\/szag062\/70500204\/szag062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T21:16:46Z","timestamp":1785964606000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/doi\/10.1093\/stcltm\/szag062\/8752872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,7,20]]}},"URL":"https:\/\/doi.org\/10.1093\/stcltm\/szag062","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,20]]},"article-number":"szag062"}}