{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:00Z","timestamp":1786121340789,"version":"build-2736575974"},"reference-count":120,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Urine-derived stem cells (UDSCs) have emerged as a promising cell source for regenerative medicine due to their non-invasive procurement, high proliferative capacity, and potential relevance to kidney-specific repair. Unlike conventional mesenchymal stem cells (MSCs) obtained from bone marrow or adipose tissue, UDSCs originate from multiple regions of the urinary tract and exhibit a unique biological profile that combines MSC characteristics with features of renal progenitor populations. This review provides a comprehensive overview of the current understanding of UDSC biology, including their origin, isolation strategies, morphology, immunophenotypic characteristics, differentiation potential, and secretory profile. Particular attention is given to the expression of renal lineage-associated markers and pluripotency-related factors that may contribute to their regenerative capacity. The bioactive mediators of UDSCs regulate inflammation, oxidative stress, angiogenesis, and extracellular matrix remodeling, thereby influencing key pathways implicated in chronic kidney disease (CKD)-associated fibrosis. Furthermore, the intrinsic renal progenitor signature of UDSCs may provide advantages in renal homing and tissue-specific repair compared with conventional MSC populations. Despite encouraging preclinical findings, significant challenges remain, including cellular heterogeneity, inconsistent isolation efficiency, lack of standardized characterization criteria, and limited clinical validation. Collectively, current evidence positions UDSCs as a biologically distinct and therapeutically attractive platform for kidney regeneration.<\/jats:p>","DOI":"10.3390\/ijms27157038","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:48:08Z","timestamp":1785948488000},"page":"7038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urine-Derived Stem Cells: Challenges in Isolation, Biological Identity, and Therapeutic Potential in CKD-Associated Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Queenesa Amabel","family":"Sunjaya","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Faried","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia"},{"name":"Department of Neurosurgery, Faculty of Medicine, Universitas Padjajaran\u2014RS UNPAD University Hospital, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"Supriyadi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia"},{"name":"Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-7430","authenticated-orcid":false,"given":"Jonny","family":"Jonny","sequence":"additional","affiliation":[{"name":"Faculty of Military Medicine, Indonesia Defense University, Bogor 16810, Indonesia"},{"name":"Department of Internal Medicine, Nephrology Division, Gatot Soebroto Central Army Hospital, Jakarta 10410, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3831-4106","authenticated-orcid":false,"given":"Hiqmah Yusi","family":"Yana","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology Division, Gatot Soebroto Central Army Hospital, Jakarta 10410, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4798639","DOI":"10.1155\/2016\/4798639","article-title":"Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence","volume":"2016","author":"Peired","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1089\/scd.2009.0196","article-title":"Not a Process of Simple Vicariousness, the Differentiation of Human Adipose-Derived Mesenchymal Stem Cells to Renal Tubular Epithelial Cells Plays an Important Role in Acute Kidney Injury Repairing","volume":"19","author":"Li","year":"2010","journal-title":"Stem Cells Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1080\/08860220902928981","article-title":"In vitro differentiation of MSC into cells with a renal tubular epithelial-like phenotype","volume":"31","author":"Singaravelu","year":"2009","journal-title":"Ren. Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrneph.2016.169","article-title":"Cellular plasticity in kidney injury and repair","volume":"13","author":"Humphreys","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.kint.2015.11.023","article-title":"Challenges and opportunities for stem cell therapy in patients with chronic kidney disease","volume":"89","author":"Hickson","year":"2016","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1016\/j.juro.2008.07.023","article-title":"Urine Derived Cells are a Potential Source for Urological Tissue Reconstruction","volume":"180","author":"Zhang","year":"2008","journal-title":"J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1186.e1","DOI":"10.1016\/j.urology.2011.12.034","article-title":"Characterization of Urine-derived Cells from Upper Urinary Tract in Patients with Bladder Cancer","volume":"79","author":"Chun","year":"2012","journal-title":"Urology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1002\/stem.1424","article-title":"Multipotential differentiation of human urine-derived stem cells: Potential for therapeutic applications in urology","volume":"31","author":"Bharadwaj","year":"2013","journal-title":"Stem Cells"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13287-018-0932-z","article-title":"Urine-derived cells for human cell therapy","volume":"9","author":"Bobrovskaya","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kim, K., Gil, M., Dayem, A.A., Choi, S., Kang, G.H., Yang, G.M., Cho, S., Jeong, Y., Kim, S.J., and Seok, J. (2020). Improved Isolation and Culture of Urine-Derived Stem Cells (USCs) and Enhanced Production of Immune Cells from the USC-Derived Induced Pluripotent Stem Cells. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030827"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.7150\/ijbs.37550","article-title":"Reno-protection of Urine-derived Stem Cells in A Chronic Kidney Disease Rat Model Induced by Renal Ischemia and Nephrotoxicity","volume":"16","author":"Zhang","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_12","unstructured":"EHL Bio Co., Ltd. (2026, February 24). A Single Arm, Open-Labelled, Dose-Escalation, Single-Center, Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Autologous Urine-Derived Stem Cells, KDSTEM Inj, in Patients with Chronic Kidney Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06071143."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bouatra, S., Aziat, F., Mandal, R., Guo, A.C., Wilson, M.R., Knox, C., Bjorndahl, T.C., Krishnamurthy, R., Saleem, F., and Liu, P. (2013). The Human Urine Metabolome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073076"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.5966\/sctm.2013-0097","article-title":"Concise Review: Stem\/Progenitor Cells for Renal Tissue Repair: Current Knowledge and Perspectives","volume":"2","author":"Aggarwal","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.transproceed.2012.01.128","article-title":"Urine Is a Highly Cytotoxic Agent: Does It Influence Stem Cell Therapies in Urology?","volume":"44","author":"Adamowicz","year":"2012","journal-title":"Transpl. Proc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.biomaterials.2012.10.038","article-title":"Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors","volume":"34","author":"Liu","year":"2013","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.gendis.2014.07.001","article-title":"Urine-derived stem cells: A novel and versatile progenitor source for cell-based therapy and regenerative medicine","volume":"1","author":"Zhang","year":"2014","journal-title":"Genes Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1002\/stem.1130","article-title":"Characterization of Renal Progenitors Committed Toward Tubular Lineage and Their Regenerative Potential in Renal Tubular Injury","volume":"30","author":"Angelotti","year":"2012","journal-title":"Stem Cells"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/sctm.18-0040","article-title":"Human Urine-Derived Stem Cell Differentiation to Endothelial Cells with Barrier Function and Nitric Oxide Production","volume":"7","author":"Liu","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Al-Marsoummi, S., Singhal, S., Garrett, S.H., Somji, S., Sens, D.A., and Singhal, S.K. (2025). CD133+CD24+ Renal Tubular Progenitor Cells Drive Hypoxic Injury Recovery via Hypoxia-Inducible Factor-1A and Epidermal Growth Factor Receptor Expression. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062472"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tcb.2016.11.003","article-title":"Extracellular Vesicles: Unique Intercellular Delivery Vehicles","volume":"27","author":"Maas","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E681","DOI":"10.1016\/j.juro.2010.02.1671","article-title":"Skeletal Muscle Derived from Human Urine-Derived Cells: A Potential Source for Injection Therapy for the Treatment of Stress Urinary Incontinence","volume":"183","author":"Bharadwaj","year":"2010","journal-title":"J. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8035076","DOI":"10.1155\/2019\/8035076","article-title":"Therapeutic Effects of Human Urine-Derived Stem Cells in a Rat Model of Cisplatin-Induced Acute Kidney Injury In Vivo and In Vitro","volume":"2019","author":"Sun","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Choi, J.Y., Chun, S.Y., Ha, Y.-S., Kim, D.H., Kim, J., Song, P.H., Kim, H.T., Yoo, E.S., Kim, B.S., and Kwon, T.G. (2017). Potency of Human Urine-Derived Stem Cells for Renal Lineage Differentiation. Tissue Engineering and Regenerative Medicine, Springer Nature Link. Available online: https:\/\/link.springer.com\/article\/10.1007\/s13770-017-0081-y.","DOI":"10.1007\/s13770-017-0081-y"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s13287-018-1035-6","article-title":"Urothelium with barrier function differentiated from human urine-derived stem cells for potential use in urinary tract reconstruction","volume":"9","author":"Wan","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13287-020-01662-2","article-title":"Hypoxic preconditioning of human urine-derived stem cell-laden small intestinal submucosa enhances wound healing potential","volume":"11","author":"Zhang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41581-022-00586-9","article-title":"Extracellular vesicles in kidney disease","volume":"18","author":"Grange","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s13287-020-01822-4","article-title":"Formation and optimization of three-dimensional organoids generated from urine-derived stem cells for renal function in vitro","volume":"11","author":"Sun","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Cheng, Y., Sun, F., Shen, J., Nasser, M.I., Zhu, P., Zhang, X., Li, Y., Yin, G., and Wang, Y. (2022). A Comprehensive Review of the Therapeutic Value of Urine-Derived Stem Cells. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.781597"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.34067\/KID.0000000000000503","article-title":"Cell Catcher: A New Method to Extract and Preserve Live Renal Cells from Urine","volume":"5","author":"Nazmutdinova","year":"2024","journal-title":"Kidney360"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Culenova, M., Nicodemou, A., Novakova, Z.V., Debreova, M., Smolinsk\u00e1, V., Bernatova, S., Ivanisova, D., Novotna, O., Vasicek, J., and Varga, I. (2021). Isolation, Culture and Comprehensive Characterization of Biological Properties of Human Urine-Derived Stem Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212503"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bento, G., Shafigullina, A.K., Rizvanov, A.A., Sard\u00e3o, V.A., Macedo, M.P., and Oliveira, P.J. (2020). Urine-Derived Stem Cells: Applications in Regenerative and Predictive Medicine. Cells, 9.","DOI":"10.3390\/cells9030573"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.tibtech.2024.01.009","article-title":"Beyond waste: Understanding urine\u2019s potential in precision medicine","volume":"42","author":"Yu","year":"2024","journal-title":"Trends Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"332","DOI":"10.62347\/PWFE2217","article-title":"Urine-derived stem cells as a model for age-related kidney degeneration and chronic disease risk","volume":"13","author":"Yu","year":"2025","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.7150\/thno.34050","article-title":"Impaired Regeneration Potential in Urinary Stem Cells Diagnosed from the Patients with Diabetic Nephropathy","volume":"9","author":"Xiong","year":"2019","journal-title":"Theranostics"},{"key":"ref_38","first-page":"Doc07","article-title":"Urinary tract infections in patients with renal insufficiency and dialysis\u2014Epidemiology, pathogenesis, clinical symptoms, diagnosis and treatment","volume":"9","author":"Scherberich","year":"2021","journal-title":"GMS Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"525","DOI":"10.4252\/wjsc.v16.i5.525","article-title":"Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury: A comparative analysis with mesenchymal stem cells","volume":"16","author":"Li","year":"2024","journal-title":"World J. Stem Cells"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"547","DOI":"10.2174\/1574888X10666150220161506","article-title":"Urine-derived Stem Cells, A New Source of Seed Cells for Tissue Engineering","volume":"11","author":"Gao","year":"2016","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Atia, G.A., Abdal Dayem, A., Taher, E.S., Alghonemy, W.Y., Cho, S.G., Aldarmahi, A.A., Haque, M.A., Alshambky, A., Taymour, N., and Ibrahim, A.M. (2025). Urine-derived stem cells: A sustainable resource for advancing personalized medicine and dental regeneration. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1571066"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1007\/s11427-018-9543-1","article-title":"Identification and characterization of two morphologically distinct stem cell subpopulations from human urine samples","volume":"63","author":"Chen","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8894449","DOI":"10.1155\/2020\/8894449","article-title":"Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells","volume":"2020","author":"Xu","year":"2020","journal-title":"Stem Cells Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.exphem.2005.07.003","article-title":"Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood","volume":"33","author":"Wagner","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s13770-017-0102-x","article-title":"Laminin and Platelet-Derived Growth Factor-BB Promote Neuronal Differentiation of Human Urine-Derived Stem Cells","volume":"15","author":"Kim","year":"2018","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"szaf002","DOI":"10.1093\/stcltm\/szaf002","article-title":"Unveiling spontaneous renal tubule-like structures from human adult renal progenitor cell spheroids derived from urine","volume":"14","author":"Giannuzzi","year":"2025","journal-title":"Stem Cells Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Larsson, H.M., Gorostidi, F., Hubbell, J.A., Barrandon, Y., and Frey, P. (2014). Clonal, Self-Renewing and Differentiating Human and Porcine Urothelial Cells, a Novel Stem Cell Population. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090006"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"918","DOI":"10.5312\/wjo.v15.i10.918","article-title":"Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases","volume":"15","author":"Yang","year":"2024","journal-title":"World J. Orthop."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shi, Y., Liu, G., Wu, R., Mack, D.L., Sun, X.S., Maxwell, J., Guan, X., Atala, A., and Zhang, Y. (2022). Differentiation Capacity of Human Urine-Derived Stem Cells to Retain Telomerase Activity. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.890574"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.4252\/wjsc.v12.i10.1080","article-title":"Urine-derived stem\/progenitor cells: A focus on their characterization and potential","volume":"12","author":"Burdeyron","year":"2020","journal-title":"World J. Stem Cells"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1681\/ASN.2007020210","article-title":"Regenerative Potential of Embryonic Renal Multipotent Progenitors in Acute Renal Failure","volume":"18","author":"Lazzeri","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1681\/ASN.2006010089","article-title":"Isolation and Characterization of Multipotent Progenitor Cells from the Bowman\u2019s Capsule of Adult Human Kidneys","volume":"17","author":"Sagrinati","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.transproceed.2016.02.078","article-title":"Generation of Mesenchymal-Like Stem Cells from Urine in Pediatric Patients","volume":"48","author":"He","year":"2016","journal-title":"Transpl. Proc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10798","DOI":"10.1111\/jcmm.14558","article-title":"Exosomal microRNA-16-5p from human urine-derived stem cells ameliorates diabetic nephropathy through protection of podocyte","volume":"25","author":"Duan","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lang, R., Liu, G., Shi, Y., Bharadwaj, S., Leng, X., Zhou, X., Liu, H., Atala, A., and Zhang, Y. (2013). Self-Renewal and Differentiation Capacity of Urine-Derived Stem Cells after Urine Preservation for 24 Hours. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053980"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc1780","article-title":"KLF4, p21 and context-dependent opposing forces in cancer","volume":"6","author":"Rowland","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41598-020-57723-2","article-title":"The FGF, TGF\u03b2 and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells","volume":"10","author":"Rahman","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1089\/scd.2010.0353","article-title":"Pluripotency Regulators in Human Mesenchymal Stem Cells: Expression of NANOG But Not of OCT-4 and SOX-2","volume":"20","author":"Pierantozzi","year":"2011","journal-title":"Stem Cells Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"419","DOI":"10.5966\/sctm.2015-0429","article-title":"Direct Isolation and Characterization of Human Nephron Progenitors","volume":"6","author":"Thornton","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1002\/emmm.201201584","article-title":"Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease","volume":"5","author":"Metsuyanim","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.jpedsurg.2012.03.034","article-title":"SIX2 and CITED1, markers of nephronic progenitor self-renewal, remain active in primitive elements of Wilms\u2019 tumor","volume":"47","author":"Murphy","year":"2012","journal-title":"J. Pediatr. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rahman, M.S., Wruck, W., Spitzhorn, L.S., Bohndorf, M., Martins, S., Asar, F., Ncube, A., Erichsen, L., Graffmann, N., and Adjaye, J. (2019). A Comprehensive Molecular Portrait of Human Urine-derived Renal Progenitor Cells. bioRxiv.","DOI":"10.1101\/602417"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0002-9440(10)62276-6","article-title":"Isolation of Renal Progenitor Cells from Adult Human Kidney","volume":"166","author":"Bussolati","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8617","DOI":"10.1016\/j.biomaterials.2013.07.077","article-title":"The effect of urine-derived stem cells expressing VEGF loaded in collagen hydrogels on myogenesis and innervation following after subcutaneous implantation in nude mice","volume":"34","author":"Liu","year":"2013","journal-title":"Biomaterials"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1016\/j.juro.2015.02.270","article-title":"Skeletal Myogenic Differentiation of Urine-Derived Stem Cells, Angiogenesis and Innervation Using Hydrogel Loaded with Growth Factors for Potential in Treatment of Urinary Incontinence","volume":"193","author":"Liu","year":"2015","journal-title":"J. Urol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Alwan, A., Khalil, F., Bowlby, J., Peko, G., Estrada, E.V., Singh, S., Deep, G., Zhang, Y., Farney, A.C., and Opara, E.C. (2024). Effect of controlled release of HGF on extracellular vesicle secretion by urine-derived stem cells. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1436296"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.ymthe.2019.11.013","article-title":"Urinary Extracellular Vesicles Carrying Klotho Improve the Recovery of Renal Function in an Acute Tubular Injury Model","volume":"28","author":"Grange","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"118792","DOI":"10.1016\/j.biopha.2025.118792","article-title":"Urine-derived stem cells: The biomedical research of endothelial and cardiovascular tissue","volume":"193","author":"Chmielewski","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wentink, M.W.J., Kalina, T., Perez-Andres, M., del Pino Molina, L., IJspeert, H., Kavelaars, F.G., Lankester, A.C., Lecrevisse, Q., van Dongen, J.J.M., and Orfao, A. (2019). Delineating Human B Cell Precursor Development with Genetically Identified PID Cases as a Model. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02680"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.21037\/tau-21-506","article-title":"Functional characterization of the immunomodulatory properties of human urine-derived stem cells","volume":"10","author":"Wu","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13287-025-04870-w","article-title":"Human urine-derived stem cells alleviate psoriasis by suppressing JAK2\/STAT3 pathway-mediated macrophage polarization","volume":"17","author":"Zhuo","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"a041415","DOI":"10.1101\/cshperspect.a041415","article-title":"Lipids in Extracellular Vesicles: What Can Be Learned about Membrane Structure and Function?","volume":"15","author":"Skotland","year":"2023","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, J., Yang, B., Qiao, R., Li, A., Guo, H., Ding, J., Li, H., Ye, H., and Wu, D. (2020). Transfer of MicroRNA-216a-5p From Exosomes Secreted by Human Urine-Derived Stem Cells Reduces Renal Ischemia\/Reperfusion Injury. Front. Cell Dev. Biol., 22.","DOI":"10.3389\/fcell.2020.610587"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"9561","DOI":"10.7150\/thno.42153","article-title":"Human urine-derived stem cells protect against renal ischemia\/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1","volume":"10","author":"Li","year":"2020","journal-title":"Theranostics"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Qian, G., Yu, Y., Dong, Y., Hong, Y., and Wang, M. (2024). Exosomes derived from human urine\u2013derived stem cells ameliorate IL-1\u03b2-induced intervertebral disk degeneration. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-07636-2"},{"key":"ref_78","first-page":"1634","article-title":"Prostaglandin E2 (PGE2) in tissue regeneration: Its role and therapeutic strategies","volume":"24","author":"Wang","year":"2025","journal-title":"EXCLI J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1093\/ecco-jcc\/jjz200","article-title":"Immunomodulatory Effect of Urine-derived Stem Cells on Inflammatory Bowel Diseases via Downregulating Th1\/Th17 Immune Responses in a PGE2-dependent Manner","volume":"14","author":"Zhou","year":"2020","journal-title":"J. Crohns Colitis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103243","DOI":"10.1016\/j.isci.2021.103243","article-title":"Renal subcapsular delivery of PGE2 promotes kidney repair by activating endogenous Sox9+ stem cells","volume":"24","author":"Chen","year":"2021","journal-title":"iScience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: From mechanisms to therapeutic medicines","volume":"8","author":"Huang","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s41392-022-01036-5","article-title":"Signaling pathways of chronic kidney diseases, implications for therapeutics","volume":"7","author":"Yuan","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41581-024-00889-z","article-title":"Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease","volume":"21","author":"Miguel","year":"2025","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e23529","DOI":"10.1002\/dvg.23529","article-title":"Epithelial\u2013mesenchymal plasticity in kidney fibrosis","volume":"62","author":"Hadpech","year":"2024","journal-title":"Genesis"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"724","DOI":"10.23876\/j.krcp.23.344","article-title":"The crosstalk of Wnt\/\u03b2-catenin signaling and p53 in acute kidney injury and chronic kidney disease","volume":"43","author":"Ming","year":"2024","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrneph.2016.54","article-title":"Developmental signalling pathways in renal fibrosis: The roles of Notch, Wnt and Hedgehog","volume":"12","author":"Edeling","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lathan, R. (2024). Exploring unconventional targets in myofibroblast transdifferentiation outside classical TGF-\u03b2 signaling in renal fibrosis. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1296504"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/ki.2008.350","article-title":"Chronic hypoxia as a mechanism of progression of chronic kidney diseases: From hypothesis to novel therapeutics","volume":"74","author":"Fine","year":"2008","journal-title":"Kidney Int."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Longhitano, E., Calabrese, V., Casuscelli, C., Carlo, S.D., Maltese, S., Romeo, A., Calanna, M., Conti, G., and Santoro, D. (2024). Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach. Medicina, 60.","DOI":"10.3390\/medicina60111821"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Panizo, S., Mart\u00ednez-Arias, L., Alonso-Montes, C., Cannata, P., Mart\u00edn-Carro, B., Fern\u00e1ndez-Mart\u00edn, J.L., Naves-D\u00edaz, M., Carrillo-L\u00f3pez, N., and Cannata-And\u00eda, J.B. (2021). Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010408"},{"key":"ref_91","unstructured":"Rout, P., Hashmi, M.F., and Baradhi, K.M. (2026, June 03). Focal Segmental Glomerulosclerosis, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK532272\/."},{"key":"ref_92","first-page":"917","article-title":"Nephrotisches Syndrom","volume":"66","author":"Braun","year":"2025","journal-title":"Inn. Med."},{"key":"ref_93","unstructured":"Merck Manual Professional Edition (2026, June 03). Nephronophthisis and Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)\u2014Nephrology. Available online: https:\/\/www.merckmanuals.com\/professional\/nephrology\/cystic-kidney-disease\/nephronophthisis-and-autosomal-dominant-tubulointerstitial-kidney-disease-adtkd."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lange-Consiglio, A., Tagliasacchi, F., Cremonesi, F., Gusmara, C., Pollera, C., Scarpa, P., Gaspari, G., and Riccaboni, P. (2025). Characterization of Urine-Derived Stromal\/Stem Cells from Healthy Dogs and Dogs Affected by Chronic Kidney Disease (CKD). Animals, 15.","DOI":"10.3390\/ani15020242"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s13770-015-0438-z","article-title":"Analysis of stability of human urine derived stem cells during serial subcultures","volume":"12","author":"Chun","year":"2015","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Kim, S.H., Jin, J.A., So, H.J., Lee, S.H., Kang, T.W., Lee, J.U., Choi, D.E., Jeong, J.Y., Chang, Y.K., and Choi, H. (2022). Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-\u03b2 Signaling Pathway. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095012"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15473287251388416","DOI":"10.1177\/15473287251388416","article-title":"Human Urine-Derived SIX2-Positive Renal Progenitor Cells Partially Improve Kidney Fibrosis by Paracrine Signaling","volume":"34","author":"Kordes","year":"2025","journal-title":"Stem Cells Dev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1681\/ASN.20213210S1790b","article-title":"Urine-Derived Stem Cells Attenuate Renal Inflammation and Fibrosis After Renal Ischemia Reperfusion: PUB085","volume":"32","author":"Choi","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/sj.ki.5002334","article-title":"Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury","volume":"72","author":"Herrera","year":"2007","journal-title":"Kidney Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9789181","DOI":"10.1155\/2021\/9789181","article-title":"Corrigendum to \u201cTherapeutic Effects of Human Urine-Derived Stem Cells in a Rat Model of Cisplatin-Induced Acute Kidney Injury In Vivo and In Vitro.\u201d","volume":"2021","author":"Sun","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"103","DOI":"10.15283\/ijsc20078","article-title":"Culturing at Low Cell Density Delays Cellular Senescence of Human Bone Marrow-Derived Mesenchymal Stem Cells in Long-Term Cultures","volume":"14","author":"Kim","year":"2021","journal-title":"Int. J. Stem Cells"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"a009100","DOI":"10.1101\/cshperspect.a009100","article-title":"Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors","volume":"5","author":"Heldin","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/joim.12019","article-title":"VEGFA and tumour angiogenesis","volume":"273","author":"Welsh","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Farooq, M., Khan, A.W., Kim, M.S., and Choi, S. (2021). The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration. Cells, 10.","DOI":"10.3390\/cells10113242"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/1573408019666230227101036","article-title":"HGF\/c-MET: A Potential Target for the Treatment of Various Cancers","volume":"19","author":"Anitha","year":"2023","journal-title":"Curr. Enzyme Inhib."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Haibe, Y., Kreidieh, M., El Hajj, H., Khalifeh, I., Mukherji, D., Temraz, S., and Shamseddine, A. (2020). Resistance Mechanisms to Anti-angiogenic Therapies in Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00221"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1016\/j.ejca.2005.08.016","article-title":"The role of IL-6 and STAT3 in inflammation and cancer","volume":"41","author":"Hodge","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1586\/1744666X.2014.894886","article-title":"The CXCL8\/IL-8 chemokine family and its receptors in inflammatory diseases","volume":"10","author":"Russo","year":"2014","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-\u03b2\/SMAD Pathway and Its Regulation in Hepatic Fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"a022061","DOI":"10.1101\/cshperspect.a022061","article-title":"TGF-\u03b2 Signaling from Receptors to Smads","volume":"8","author":"Hata","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"7211","DOI":"10.1002\/jcp.30375","article-title":"The molecular structure and role of CCL2 (MCP-1) and C-C chemokine receptor CCR2 in skeletal biology and diseases","volume":"236","author":"Zhu","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/mmi.15168","article-title":"Extracellular vesicles biogenesis and uptake concepts: A comprehensive guide to studying host\u2013pathogen communication","volume":"122","author":"Sabatke","year":"2024","journal-title":"Mol. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ymeth.2008.03.006","article-title":"Adipose-derived stem cells: Isolation, expansion and differentiation","volume":"45","author":"Bunnell","year":"2008","journal-title":"Methods"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1002\/sctm.17-0129","article-title":"Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine","volume":"6","author":"Samsonraj","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.stem.2009.02.001","article-title":"Mesenchymal Stem Cell Homing: The Devil Is in the Details","volume":"4","author":"Karp","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/scd.2008.0253","article-title":"Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect","volume":"18","author":"Fischer","year":"2009","journal-title":"Stem Cells Dev."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s13287-020-01642-6","article-title":"Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats","volume":"11","author":"Ishiuchi","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Ceccotti, E., Quaglia, M., Camussi, G., and Bruno, S. (2025). Mesenchymal stem cells derived extracellular vesicles for chronic kidney disease: Pleiotropic mechanisms of actions of a versatile therapy. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1612193"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1007\/s12015-021-10155-5","article-title":"Extracellular Vesicles from Human Adipose-Derived Mesenchymal Stem Cells: A Review of Common Cargos","volume":"18","author":"Diebold","year":"2022","journal-title":"Stem Cell Rev. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/7038\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:16:52Z","timestamp":1786076212000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/7038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":120,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27157038"],"URL":"https:\/\/doi.org\/10.3390\/ijms27157038","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}