{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:35:39Z","timestamp":1779197739374,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Induced pluripotent stem cell (iPSC)-derived kidney organoids are a potential tool for the regeneration of kidney tissue. They represent an early stage of nephrogenesis and have been shown to successfsully vascularize and mature further in vivo. However, there are concerns regarding the long-term safety and stability of iPSC derivatives. Specifically, the potential for tumorigenesis may impede the road to clinical application. To study safety and stability of kidney organoids, we analyzed their potential for malignant transformation in a teratoma assay and following long-term subcutaneous implantation in an immune-deficient mouse model. We did not detect fully functional residual iPSCs in the kidney organoids as analyzed by gene expression analysis, single-cell sequencing and immunohistochemistry. Accordingly, kidney organoids failed to form teratoma. Upon long-term subcutaneous implantation of whole organoids in immunodeficient IL2Ry\u2212\/\u2212RAG2\u2212\/\u2212 mice, we observed tumor formation in 5 out of 103 implanted kidney organoids. These tumors were composed of WT1+CD56+ immature blastemal cells and showed histological resemblance with Wilms tumor. No genetic changes were identified that contributed to the occurrence of tumorigenic cells within the kidney organoids. However, assessment of epigenetic changes revealed a unique cluster of differentially methylated genes that were also present in undifferentiated iPSCs. We discovered that kidney organoids have the capacity to form tumors upon long-term implantation. The presence of epigenetic modifications combined with the lack of environmental cues may have caused an arrest in terminal differentiation. Our results indicate that the safe implementation of kidney organoids should exclude the presence of pro-tumorigenic methylation in kidney organoids.<\/jats:p>","DOI":"10.1093\/stmcls\/sxac009","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T20:11:03Z","timestamp":1645215063000},"page":"577-591","source":"Crossref","is-referenced-by-count":13,"title":["Kidney Organoids Are Capable of Forming Tumors, but Not Teratomas"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-2321","authenticated-orcid":false,"given":"Anusha S","family":"Shankar","sequence":"first","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Internal Medicine, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyu","family":"Du","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Internal Medicine, 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Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sander S","family":"Korevaar","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute, Department of Internal Medicine, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Boers","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and iPS Core Facility, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilfred F J","family":"van IJcken","sequence":"additional","affiliation":[{"name":"Center for Biomics, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric M J","family":"Bindels","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert","family":"Eussen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelies","family":"de Klein","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9982-6184","authenticated-orcid":false,"given":"Qiuwei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey","family":"Oudijk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian C","family":"Clahsen-van Groningen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8738-3571","authenticated-orcid":false,"given":"Ewout J","family":"Hoorn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla 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