The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells
Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ transplantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidne...
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| Format: | Artykuł |
| Język: | English |
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MDPI AG
2022-02-01
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| Seria: | Cells |
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| Dostęp online: | https://www.mdpi.com/2073-4409/11/4/635 |
| _version_ | 1827656366996586496 |
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| author | Lisa Nguyen Wasco Wruck Lars Erichsen Nina Graffmann James Adjaye |
| author_facet | Lisa Nguyen Wasco Wruck Lars Erichsen Nina Graffmann James Adjaye |
| author_sort | Lisa Nguyen |
| collection | DOAJ |
| description | Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ transplantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidney diseases and the development of prospective therapeutic options are urgently needed. Within the kidney, the glomeruli are involved in blood filtration and waste excretion and are easily affected by changing cellular conditions. Puromycin aminonucleoside (PAN) is a nephrotoxin, which can be employed to induce acute glomerular damage and to model glomerular disease. For this reason, we generated kidney organoids from three iPSC lines and treated these with PAN in order to induce kidney injury. Morphological observations revealed the disruption of glomerular and tubular structures within the kidney organoids upon PAN treatment, which were confirmed by transcriptome analyses. Subsequent analyses revealed an upregulation of immune response as well as inflammatory and cell-death-related processes. We conclude that the treatment of iPSC-derived kidney organoids with PAN induces kidney injury mediated by an intertwined network of inflammation, cytoskeletal re-arrangement, DNA damage, apoptosis and cell death. Furthermore, urine-stem-cell-derived kidney organoids can be used to model kidney-associated diseases and drug discovery. |
| first_indexed | 2024-03-09T22:21:36Z |
| format | Article |
| id | doaj.art-dbc5dba3ca4045e9b63aa236ce45c163 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:21:36Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-dbc5dba3ca4045e9b63aa236ce45c1632023-11-23T19:14:29ZengMDPI AGCells2073-44092022-02-0111463510.3390/cells11040635The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem CellsLisa Nguyen0Wasco Wruck1Lars Erichsen2Nina Graffmann3James Adjaye4Institute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, GermanyInstitute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, GermanyInstitute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, GermanyInstitute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, GermanyInstitute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, GermanyKidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ transplantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidney diseases and the development of prospective therapeutic options are urgently needed. Within the kidney, the glomeruli are involved in blood filtration and waste excretion and are easily affected by changing cellular conditions. Puromycin aminonucleoside (PAN) is a nephrotoxin, which can be employed to induce acute glomerular damage and to model glomerular disease. For this reason, we generated kidney organoids from three iPSC lines and treated these with PAN in order to induce kidney injury. Morphological observations revealed the disruption of glomerular and tubular structures within the kidney organoids upon PAN treatment, which were confirmed by transcriptome analyses. Subsequent analyses revealed an upregulation of immune response as well as inflammatory and cell-death-related processes. We conclude that the treatment of iPSC-derived kidney organoids with PAN induces kidney injury mediated by an intertwined network of inflammation, cytoskeletal re-arrangement, DNA damage, apoptosis and cell death. Furthermore, urine-stem-cell-derived kidney organoids can be used to model kidney-associated diseases and drug discovery.https://www.mdpi.com/2073-4409/11/4/635urine cellsiPSCsorganoidspuromycin aminonucleosideAKIinflammation |
| spellingShingle | Lisa Nguyen Wasco Wruck Lars Erichsen Nina Graffmann James Adjaye The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells Cells urine cells iPSCs organoids puromycin aminonucleoside AKI inflammation |
| title | The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells |
| title_full | The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells |
| title_fullStr | The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells |
| title_full_unstemmed | The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells |
| title_short | The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells |
| title_sort | nephrotoxin puromycin aminonucleoside induces injury in kidney organoids differentiated from induced pluripotent stem cells |
| topic | urine cells iPSCs organoids puromycin aminonucleoside AKI inflammation |
| url | https://www.mdpi.com/2073-4409/11/4/635 |
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