{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T00:27:11Z","timestamp":1793752031338,"version":"4.6.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidade Federal De S\u00e3o Paulo","id":[{"id":"https:\/\/ror.org\/02k5swt12","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int Urogynecol J"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction and Hypothesis<\/jats:title>\n                    <jats:p>Stem cell therapy for stress urinary incontinence (SUI) has been pursued for more than a decade, supported by a compelling regenerative rationale and reassuring early-phase safety data. Yet clinical efficacy has remained modest, complete continence uncommon, and durability uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>In this Clinical Opinion, we argue that translation has stalled for reasons that are both biological and conceptual: heterogeneous cell products and manufacturing variability undermine reproducibility; endpoints and follow-up are insufficiently harmonized to benchmark against surgical standards; chronically fibrotic periurethral tissue may be biologically quiescent and poorly permissive for regenerative activation; and, fundamentally, continence is a biomechanical phenomenon that cell injections alone cannot replicate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We propose that future progress will depend on validated potency assays, mechanism-driven trial design, microenvironment priming strategies, and integration of regenerative biology with biomechanical reinforcement (e.g., scaffolds or biologically enhanced support constructs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Until such integration occurs, stem cell therapy for SUI should remain investigational.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00192-026-06830-1","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T12:08:12Z","timestamp":1787400492000},"page":"3215-3220","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stem Cell Therapy for Stress Urinary Incontinence: Why Has Clinical Success Remained Limited?"],"prefix":"10.1007","volume":"37","author":[{"given":"Rodrigo A.","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"6830_CR1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s00192-015-2932-1","volume":"27","author":"BT Haylen","year":"2016","unstructured":"Haylen BT, Maher C, Barber MD, Camargo S, Dandolu V, Digesu A, et al. An International Urogynecological Association (IUGA)\/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2016;27:165\u201378.","journal-title":"Int Urogynecol J"},{"key":"6830_CR2","volume-title":"Incontinence","year":"2017","unstructured":"Abrams P, Cardozo L, Wagg A, Wein A, editors. Incontinence. 6th ed. Bristol: International Continence Society; 2017.","edition":"6th ed"},{"issue":"7","key":"6830_CR3","doi-asserted-by":"publisher","first-page":"CD006375","DOI":"10.1002\/14651858.CD006375.pub3","volume":"7","author":"AA Ford","year":"2017","unstructured":"Ford AA, Rogerson L, Cody JD, Ogah J. Mid-urethral sling operations for stress urinary incontinence in women. Cochrane Database Syst Rev. 2017;7:CD006375.","journal-title":"Cochrane Database Syst Rev"},{"key":"6830_CR4","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1016\/S0002-9378(12)91840-2","volume":"170","author":"JO DeLancey","year":"1994","unstructured":"DeLancey JO. Structural support of the urethra as it relates to stress urinary incontinence. Am J Obstet Gynecol. 1994;170:1713\u201320.","journal-title":"Am J Obstet Gynecol"},{"key":"6830_CR5","first-page":"2263","volume":"179","author":"LK Carr","year":"2008","unstructured":"Carr LK, Steele D, Steele S, Wagner D, Pruchnic R, Jankowski R, et al. 1-year follow-up of autologous muscle-derived stem cell injection pilot study for stress urinary incontinence. J Urol. 2008;179:2263\u20138.","journal-title":"J Urol"},{"key":"6830_CR6","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.juro.2014.02.047","volume":"192","author":"KM Peters","year":"2014","unstructured":"Peters KM, Dmochowski RR, Carr LK, Robert M, Kaufman MR, Sirls LT, et al. Autologous muscle-derived cells for treatment of stress urinary incontinence in women: a dose-ranging study. J Urol. 2014;192:1053\u20139.","journal-title":"J Urol"},{"key":"6830_CR7","unstructured":"Sharifiagdas F, Taheri M, Moghadasali R,\u00a0Shekarchian S, Jaroughi N, Bolurieh T,\u00a0et al.\u00a0Autologous muscle-derived cell injection for treatment of female stress urinary incontinence: a single-arm clinicaltrial with 24-months follow-up. Urol J. 2019;16:482\u2013487"},{"key":"6830_CR8","first-page":"1763","volume":"33","author":"J Choi","year":"2022","unstructured":"Choi J, Lee HN, Kim JH, Cho MK. Stem cell therapy for stress urinary incontinence: current status and future directions. Int Urogynecol J. 2022;33:1763\u201375.","journal-title":"Int Urogynecol J"},{"key":"6830_CR9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/MOU.0b013e3283632115","volume":"23","author":"N Mangir","year":"2013","unstructured":"Mangir N, Chapple CR. Stem cell therapy for stress urinary incontinence: biological plausibility and clinical reality. Curr Opin Urol. 2013;23:399\u2013404.","journal-title":"Curr Opin Urol"},{"key":"6830_CR10","first-page":"119","volume":"21","author":"S Neri","year":"2019","unstructured":"Neri S. Genetic stability of mesenchymal stromal cells for clinical use: a critical review. Cytotherapy. 2019;21:119\u201327.","journal-title":"Cytotherapy"},{"key":"6830_CR11","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1002\/sctm.17-0051","volume":"6","author":"AI Caplan","year":"2017","unstructured":"Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Translat Med. 2017;6:1445\u201351.","journal-title":"Stem Cells Translat Med"},{"key":"6830_CR12","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.stem.2018.05.004","volume":"22","author":"J Galipeau","year":"2018","unstructured":"Galipeau J, Sens\u00e9b\u00e9 L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22:824\u201333.","journal-title":"Cell Stem Cell"},{"key":"6830_CR13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1089\/hum.2010.197","volume":"22","author":"L Senseb\u00e9","year":"2011","unstructured":"Senseb\u00e9 L, Bourin P, Tarte K. Good manufacturing practices production of mesenchymal stem\/stromal cells. Hum Gene Ther. 2011;22:19\u201326.","journal-title":"Hum Gene Ther"},{"key":"6830_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.94","volume":"45","author":"MB Murphy","year":"2013","unstructured":"Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics. Exp Mol Med. 2013;45:e54.","journal-title":"Exp Mol Med"},{"key":"6830_CR15","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41536-019-0083-6","volume":"4","author":"MF Pittenger","year":"2019","unstructured":"Pittenger MF, Discher DE, P\u00e9ault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22.","journal-title":"NPJ Regen Med"},{"key":"6830_CR16","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.stem.2015.06.007","volume":"17","author":"A Trounson","year":"2015","unstructured":"Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11\u201322.","journal-title":"Cell Stem Cell"},{"key":"6830_CR17","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1161\/CIRCRESAHA.114.300639","volume":"114","author":"S Sahoo","year":"2014","unstructured":"Sahoo S, Losordo DW. Exosomes and cardiac repair after myocardial infarction. Circ Res. 2014;114:333\u201344.","journal-title":"Circ Res"},{"key":"6830_CR18","first-page":"161","volume":"1416","author":"L Senseb\u00e9","year":"2016","unstructured":"Senseb\u00e9 L, Gadelorge M, Fleury-Cappellesso S. Production of mesenchymal stromal cells according to GMP standards. Methods Mol Biol. 2016;1416:161\u201375.","journal-title":"Methods Mol Biol."},{"key":"6830_CR19","doi-asserted-by":"crossref","unstructured":"Tommaselli GA, Di Carlo C, Formisano C, Fabozzi A, Nappi C. Medium-term and long-term outcomes following placement of midurethral slings for stress urinary incontinence: a systematic review and meta analysis. Int Urogynecol J. 2015;26:1253\u20131268.","DOI":"10.1007\/s00192-015-2645-5"},{"key":"6830_CR20","unstructured":"U.S. Food and Drug Administration. Considerations for the design of early-phase clinical trials of cellular and gene therapy products: guidance for industry. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD. 2015."},{"key":"6830_CR21","unstructured":"European Medicines Agency. Guideline on human cell-based medicinal products. EMA\/CHMP\/410869\/2006. London: EMA; 2008."},{"key":"6830_CR22","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1002\/nau.20232","volume":"26","author":"PW Hodges","year":"2007","unstructured":"Hodges PW, Sapsford R, Pengel LH. Postural and respiratory functions of the pelvic floor muscles. Neurourol Urodyn. 2007;26:362\u201371.","journal-title":"Neurourol Urodyn"},{"key":"6830_CR23","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1600-0412.1990.tb08027.x","volume":"153","author":"PE Petros","year":"1990","unstructured":"Petros PE, Ulmsten U. An integral theory of female urinary incontinence. Acta Obstet Gynecol Scand Suppl. 1990;153:7\u201331.","journal-title":"Acta Obstet Gynecol Scand Suppl"}],"container-title":["International Urogynecology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00192-026-06830-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00192-026-06830-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00192-026-06830-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T00:06:49Z","timestamp":1793750809000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00192-026-06830-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["6830"],"URL":"https:\/\/doi.org\/10.1007\/s00192-026-06830-1","relation":{},"ISSN":["0937-3462","1433-3023"],"issn-type":[{"value":"0937-3462","type":"print"},{"value":"1433-3023","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]},"assertion":[{"value":"12 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"None.","order":1,"name":"Ethics","label":"Conflicts of Interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}