{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:59:34Z","timestamp":1760151574349,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nephropathic cystinosis is an inherited lysosomal storage disorder caused by pathogenic variants in the cystinosin (CTNS) gene and is characterized by the excessive shedding of proximal tubular epithelial cells (PTECs) and podocytes into urine, development of the renal Fanconi syndrome and end-stage kidney disease (ESKD). We hypothesized that in compensation for epithelial cell losses, cystinosis kidneys undertake a regenerative effort, and searched for the presence of kidney progenitor cells (KPCs) in the urine of cystinosis patients. Urine was cultured in a specific progenitor medium to isolate undifferentiated cells. Of these, clones were characterized by qPCR, subjected to a differentiation protocol to PTECs and podocytes and assessed by qPCR, Western blot, immunostainings and functional assays. Cystinosis patients voided high numbers of undifferentiated cells in urine, of which various clonal cell lines showed a high capacity for self-renewal and expressed kidney progenitor markers, which therefore were assigned as cystinosis urine-derived KPCs (Cys-uKPCs). Cys-uKPC clones showed the capacity to differentiate between functional PTECs and\/or podocytes. Gene addition with wild-type CTNS using lentiviral vector technology resulted in significant reductions in cystine levels. We conclude that KPCs present in the urine of cystinosis patients can be isolated, differentiated and complemented with CTNS in vitro, serving as a novel tool for disease modeling.<\/jats:p>","DOI":"10.3390\/cells11071245","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T16:21:30Z","timestamp":1649262090000},"page":"1245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Urine-Derived Kidney Progenitor Cells in Cystinosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Koenraad","family":"Veys","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Hospitals Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"},{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-7360","authenticated-orcid":false,"given":"Sante Princiero","family":"Berlingerio","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dries","family":"David","sequence":"additional","affiliation":[{"name":"Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-6400","authenticated-orcid":false,"given":"Tjessa","family":"Bondue","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1727-9517","authenticated-orcid":false,"given":"Katharina","family":"Held","sequence":"additional","affiliation":[{"name":"Laboratory of Endometrium, Endometriosis & Reproductive Medicine (LEERM), Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Reda","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-9921","authenticated-orcid":false,"given":"Martijn van den","family":"Broek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6524 Nijmegen, The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud University Medical Center, 6524 Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen","family":"Theunis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9977","authenticated-orcid":false,"given":"Mirian","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6524 Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1156-5264","authenticated-orcid":false,"given":"Elisabeth","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud University Medical Center, 6524 Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2502-0409","authenticated-orcid":false,"given":"Joris","family":"Vriens","sequence":"additional","affiliation":[{"name":"Laboratory of Endometrium, Endometriosis & Reproductive Medicine (LEERM), Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Diomedi-Camassei","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"Gijsbers","sequence":"additional","affiliation":[{"name":"Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"},{"name":"Leuven Viral Vector Core, KU Leuven, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambertus van den","family":"Heuvel","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"},{"name":"Department of Pediatrics, Division of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud University Medical Center, 6524 Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2207-9699","authenticated-orcid":false,"given":"Fanny O.","family":"Arcolino","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-7312","authenticated-orcid":false,"given":"Elena","family":"Levtchenko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospitals Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"},{"name":"Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven Campus Gasthuisberg, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ng0498-319","article-title":"A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis","volume":"18","author":"Town","year":"1998","journal-title":"Nat. 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