{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:49Z","timestamp":1785427249295,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00333544"],"award-info":[{"award-number":["RS-2024-00333544"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00333544"],"award-info":[{"award-number":["RS-2024-00333544"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Progressive bladder fibrosis and impaired detrusor function represent converging pathological endpoints across diverse bladder disorders, including bladder outlet obstruction (BOO) associated with benign prostatic hyperplasia, spinal cord injury (SCI)-induced neurogenic bladder, radiation cystitis, and interstitial cystitis\/bladder pain syndrome. Conventional therapies primarily manage symptoms and rarely reverse established fibrosis or restore durable bladder homeostasis. Mesenchymal stem\/stromal cells (MSCs) have attracted considerable interest as therapeutic agents owing to their antifibrotic, immunomodulatory, angiogenic, and trophic paracrine activities. This review synthesises six key studies from our group and places them within the broader international literature on bladder regenerative medicine: (i) feasibility of superparamagnetic iron oxide (SPIO)-based molecular MRI tracking of transplanted human MSCs (hMSCs) in the bladder; (ii) SPIO-hMSC therapy for BOO-associated fibrosis with concurrent MRI monitoring; (iii) hepatocyte growth factor (HGF)-overexpressing engineered hMSC (B10.HGF) therapy in BOO; (iv) hMSC transplantation into the SCI-injured bladder wall monitored by MRI; (v) systematic review and meta-analysis of stem cell therapy effects on urodynamic outcomes in SCI models; and (vi) HGF-overexpressing hMSC therapy for BOO-induced underactive bladder. These six key studies are contextualised within the broader literature addressing cell sources, biomaterial-assisted delivery platforms, mechanistic pathways, emerging clinical evidence, and the evolving regulatory landscape for cell-based advanced therapy medicinal products. Key translational challenges include product standardisation, long-term durability, and mechanism-linked potency assay development.<\/jats:p>","DOI":"10.3390\/cimb48070658","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:11:57Z","timestamp":1782785517000},"page":"658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stem Cell-Based Strategies for Fibrotic and Neurogenic Bladder Disorders: Current Evidence, Translational Challenges, and Future Directions"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-3610","authenticated-orcid":false,"given":"Jae Heon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Urology, Soonchunhyang University School of Medicine, Seoul 140-743, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8345-6686","authenticated-orcid":false,"given":"Miho","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology, Soonchunhyang University School of Medicine, Seoul 140-743, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Seob","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology, Soonchunhyang University School of Medicine, Seoul 140-743, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lu, Y., Manson, S.R., de Araujo, I.B.B.A., Austin, P.F., Djurhuus, J.C., Olsen, L.H., and N\u00f8rregaard, R. (2022). The release of 24 h infravesical obstruction in mice: Changes in molecular, morphological, and functional parameters for 14-day observation. Front. Med., 9.","DOI":"10.3389\/fmed.2022.892746"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, H.Y., Wang, C.-S., and Juan, Y.-S. (2022). Detrusor underactivity in men with bladder outlet obstruction. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112954"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/nau.20351","article-title":"Monitoring transplanted human mesenchymal stem cells in rat and rabbit bladders using molecular magnetic resonance imaging","volume":"26","author":"Song","year":"2007","journal-title":"Neurourol. Urodyn."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3727\/096368911X627516","article-title":"Inhibition of collagen deposit in obstructed rat bladder outlet by transplantation of superparamagnetic iron oxide-labeled human mesenchymal stem cells as monitored by molecular magnetic resonance imaging","volume":"21","author":"Lee","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.3727\/096368912X637488","article-title":"Mesenchymal stem cells overexpressing hepatocyte growth factor inhibit collagen deposit and improve bladder function in rat model of bladder outlet obstruction","volume":"21","author":"Song","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.3727\/096368914X682125","article-title":"Improvement in spinal cord injury-induced bladder fibrosis using mesenchymal stem cell transplantation into the bladder wall","volume":"24","author":"Lee","year":"2015","journal-title":"Cell Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Shim, S.R., Doo, S.W., Yang, W.J., Yoo, B.W., Kim, J.M., Ko, Y.M., Song, E.S., Lim, I.S., and Lee, H.J. (2015). Bladder recovery by stem cell based cell therapy in the bladder dysfunction induced by spinal cord injury: Systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0113491"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Yang, H.J., Choi, S.S., Kim, S.U., Lee, H.J., and Song, Y.S. (2021). Improved bladder contractility after transplantation of human mesenchymal stem cells overexpressing hepatocyte growth factor into underactive bladder from bladder outlet obstruction models of rats. PLoS ONE, 16, Erratum in: PLoS ONE. 2022, 17, e0269577.","DOI":"10.1371\/journal.pone.0269577"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.reth.2024.12.005","article-title":"Stem cell therapy for bladder regeneration: A comprehensive systematic review","volume":"28","author":"Faegh","year":"2025","journal-title":"Regen. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1007\/s12015-022-10340-0","article-title":"Human urine-derived stem cells improve partial bladder outlet obstruction in rats: Preliminary data and microRNA\u2013mRNA expression profile","volume":"18","author":"Tu","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1093\/stcltm\/szac065","article-title":"Safety of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells for Treating Interstitial Cystitis: A Phase I Study","volume":"11","author":"Shin","year":"2022","journal-title":"Stem Cells Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101763","DOI":"10.1016\/j.cont.2025.101763","article-title":"Factors contributing to bladder fibrosis","volume":"14","author":"Andersson","year":"2025","journal-title":"Continence"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wei, H., Zhu, C., Huang, Q., Yang, J., Li, Y.-T., Zhang, Y.-G., Li, B.-H., and Zi, H. (2025). Global, regional, and national burden of benign prostatic hyperplasia from 1990 to 2021 and projection to 2035. BMC Urol., 25.","DOI":"10.1186\/s12894-025-01715-9"},{"key":"ref_14","unstructured":"World Health Organization (2024, December 13). Spinal Cord Injury Fact Sheet. Available online: https:\/\/www.who.int\/health-topics\/spinal-cord-injury."},{"key":"ref_15","unstructured":"U.S. Food and Drug Administration (2020). Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8872","DOI":"10.1038\/s41598-017-09330-x","article-title":"Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1007\/s12015-022-10343-x","article-title":"Iron oxide nanoparticles in mesenchymal stem cell detection and therapy","volume":"18","author":"Mehta","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1111\/jcmm.17497","article-title":"Recent advances in the therapeutic efficacy of hepatocyte growth factor gene-modified mesenchymal stem cells in multiple disease settings","volume":"26","author":"Meng","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1097\/01.ASN.0000130568.53923.FD","article-title":"Hepatocyte growth factor antagonizes the profibrotic action of TGF-\u03b21 in mesangial cells by stabilizing Smad transcriptional corepressor TGIF","volume":"15","author":"Dai","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13287-022-02739-w","article-title":"Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder","volume":"13","author":"Liu","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4844","DOI":"10.1080\/21655979.2022.2036397","article-title":"Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via p38 MAPK\/NF-\u03baB pathway","volume":"13","author":"Li","year":"2022","journal-title":"Bioengineered"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.1038\/s41598-022-10640-y","article-title":"Human amniotic fluid stem cells can alleviate detrusor dysfunction caused by bladder outlet obstruction in rats","volume":"12","author":"Liang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123551","DOI":"10.1016\/j.biomaterials.2025.123551","article-title":"Magnetically controlled microgelbots with stem cells for the treatment of interstitial cystitis","volume":"325","author":"Choi","year":"2026","journal-title":"Biomaterials"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1186\/s13287-022-03188-1","article-title":"Implantation of adipose-derived mesenchymal stem cell sheets promotes axonal regeneration and restores bladder function after spinal cord injury","volume":"13","author":"Chen","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1039\/D3TB02837B","article-title":"Hydrogel: A new material for intravesical drug delivery after bladder cancer surgery","volume":"12","author":"Wu","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13287-022-03230-2","article-title":"Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis","volume":"14","author":"Brossard","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.21037\/tau-2025-234","article-title":"Assessments of neurogenic bladder dysfunction induced by spinal cord injury, bladder outlet obstruction and diabetes: A comparative study of rat models","volume":"14","author":"Sun","year":"2025","journal-title":"Transl. Androl. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"szaf018","DOI":"10.1093\/stcltm\/szaf018","article-title":"A single-center, phase 1\/2a trial of hESC-derived mesenchymal stem cells (MR-MC-01) for safety and efficacy in interstitial cystitis patients","volume":"14","author":"Kyung","year":"2025","journal-title":"Stem Cells Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13287-023-03294-8","article-title":"Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: Open clinical trial","volume":"14","author":"Coelho","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1002\/sctm.19-0431","article-title":"Two phase I\/II clinical trials for the treatment of urinary incontinence with autologous mesenchymal stem cells","volume":"9","author":"Bravo","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"123402","DOI":"10.1016\/j.wneu.2024.10.131","article-title":"Improvement of neurogenic bladder dysfunction following combined cell therapy with mesenchymal stem cell and Schwann cell in spinal cord injury: A randomized, open-label, phase II clinical trial","volume":"194","author":"Akhlaghpasand","year":"2025","journal-title":"World Neurosurg."},{"key":"ref_32","unstructured":"U.S. Food and Drug Administration (2024, December 18). FDA Approves Remestemcel-L-rknd (Ryoncil) for Steroid-Refractory Acute Graft-Versus-Host Disease in Pediatric Patients, Available online: https:\/\/www.fda.gov."},{"key":"ref_33","unstructured":"European Medicines Agency (2024, December 13). Advanced Therapy Medicinal Products (ATMPs): Overview. Regulation (EC) No 1394\/2007. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/advanced-therapy-medicinal-products."},{"key":"ref_34","unstructured":"European Medicines Agency (2024, December 13). Alofisel (darvadstrocel): Withdrawal of the Marketing Authorisation in the European Union. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/alofisel."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.stemcr.2021.05.012","article-title":"ISSCR guidelines for stem cell research and clinical translation: The 2021 update","volume":"16","author":"Anthony","year":"2021","journal-title":"Stem Cell Rep."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:29:20Z","timestamp":1782793760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070658"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070658","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}