{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:05:47Z","timestamp":1789135547412,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Progressive multiple sclerosis (PMS) is a disabling demyelinating disease characterized by irreversible neurodegeneration. Unlike relapsing-remitting MS, for which many disease-modifying therapies exist, treatment options for PMS are extremely limited. Only two agents (ocrelizumab and siponimod) have modest efficacy, and no effective therapies exist for non-active disease. Mesenchymal stem cell (MSC) transplantation has emerged as a promising strategy due to its immunomodulatory and neurotrophic properties. However, clinical trials have yielded inconsistent results, and prior meta-analyses were limited by mixed MS subtypes and non-randomized studies, leaving uncertainty about MSC\u2019s clinical utility in PMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To rigorously evaluate the efficacy and safety of MSC transplantation in PMS patients through a systematic review and meta-analysis of exclusively randomized controlled trials (RCTs), and to provide evidence-based recommendations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two researchers searched PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases from inception to March 2026. RCTs comparing MSC transplantation with placebo in adult PMS patients were included. Primary outcome: change in Expanded Disability Status Scale (EDSS) score. Secondary outcomes: treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Meta-analysis used RevMan 5.4 with random\/fixed-effects models. Certainty of evidence was assessed by GRADE. Protocol registered on PROSPERO (CRD420261301154).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three RCTs (143 patients; 75 MSC, 68 control) were included. MSC therapy did not significantly improve EDSS scores (pooled MD = -0.08, 95% CI -0.38 to 0.22,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.61;\n                      <jats:italic>I\u00b2<\/jats:italic>\n                      \u00a0=\u00a066%). MSC did not increase TEAEs (RR\u00a0=\u00a01.08, 95% CI 0.86 to 1.35,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.52) or SAEs (RR\u00a0=\u00a00.79, 95% CI 0.26 to 2.36,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.67). GRADE: moderate certainty for TEAEs, very low for EDSS change and SAEs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MSC transplantation appears safe in PMS patients, with no increased adverse event risk. However, current evidence does not support significant benefit on EDSS scores in unselected patients. Given the very low to moderate certainty, further high-quality RCTs are warranted.<\/jats:p>\n                    <jats:p>This systematic review and meta-analysis was conducted in strict accordance with the Cochrane Handbook for Systematic Reviews of Interventions (version 6.5) and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines[24, 25]. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD420261301154) prior to literature screening and data extraction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1861624","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:48:20Z","timestamp":1784695700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of mesenchymal stem cell transplantation for progressive multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials with clinical implications for patient stratification and treatment optimization"],"prefix":"10.3389","volume":"17","author":[{"given":"Honghao","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuting","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University","place":["Nanjing, Jiangsu, China"]},{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s13317-019-0117-5","article-title":"Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options","volume":"10","author":"Andravizou","year":"2019","journal-title":"Auto Immun Highl"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.amjmed.2020.05.049","article-title":"Treatment of multiple sclerosis: a review","volume":"133","author":"Hauser","year":"2020","journal-title":"Am J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0953-0","article-title":"Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity","volume":"123","author":"Antel","year":"2012","journal-title":"Acta Neuropathol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ncl.2017.08.003","article-title":"New insights into multiple sclerosis clinical course from the topographical model and functional reserve","volume":"36","author":"Krieger","year":"2018","journal-title":"Neurol Clin"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult Scler"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1210091","article-title":"Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. 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