{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:27:19Z","timestamp":1788200839442,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["417677437\/GRK2578"],"award-info":[{"award-number":["417677437\/GRK2578"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the re-acquisition of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it is crucial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, which exhibited similar morphology to PTEC, expressed prototypical PTEC markers, and were able to undergo albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.<\/jats:p>","DOI":"10.3390\/ijms25010081","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T07:20:31Z","timestamp":1703056831000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins"],"prefix":"10.3390","volume":"25","author":[{"given":"Isaac Musong","family":"Mboni-Johnston","sequence":"first","affiliation":[{"name":"Institute of Toxicology, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazih Mohamed Zakari","family":"Kouidrat","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas Georg","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Mei\u00dfner","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-6761","authenticated-orcid":false,"given":"James","family":"Adjaye","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Zayed Centre for Research into Rare Diseases in Children (ZCR), EGA Institute for Women\u2019s Health, University College London (UCL), 20 Guilford Street, London WC1N 1DZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1836-6348","authenticated-orcid":false,"given":"Nicole","family":"Schupp","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Medical Faculty and University Hospital, University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1021\/mp400720w","article-title":"Drug-induced nephrotoxicity: Clinical impact and preclinical in vitro models","volume":"11","author":"Tiong","year":"2014","journal-title":"Mol. 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