A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids
Abstract Kidneys are complex organs, and reproducing their function and physiology in a laboratory setting remains difficult. During drug development, potential compounds may exhibit unexpected nephrotoxic effects, which imposes a significant financial burden on pharmaceutical companies. As a result...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33110-5 |
| _version_ | 1797845950834671616 |
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| author | Jasmin Dilz Isabel Auge Kathrin Groeneveld Stefanie Reuter Ralf Mrowka |
| author_facet | Jasmin Dilz Isabel Auge Kathrin Groeneveld Stefanie Reuter Ralf Mrowka |
| author_sort | Jasmin Dilz |
| collection | DOAJ |
| description | Abstract Kidneys are complex organs, and reproducing their function and physiology in a laboratory setting remains difficult. During drug development, potential compounds may exhibit unexpected nephrotoxic effects, which imposes a significant financial burden on pharmaceutical companies. As a result, there is an ongoing need for more accurate model systems. The use of renal organoids to simulate responses to nephrotoxic insults has the potential to bridge the gap between preclinical drug efficacy studies in cell cultures and animal models, and the stages of clinical trials in humans. Here we established an accessible fluorescent whole-mount approach for nuclear and membrane staining to first provide an overview of the organoid histology. Furthermore, we investigated the potential of renal organoids to model responses to drug toxicity. For this purpose, organoids were treated with the chemotherapeutic agent doxorubicin for 48 h. When cell viability was assessed biochemically, the organoids demonstrated a significant, dose-dependent decline in response to the treatment. Confocal microscopy revealed visible tubular disintegration and a loss of cellular boundaries at high drug concentrations. This observation was further reinforced by a dose-dependent decrease of the nuclear area in the analyzed images. In contrast to other approaches, in this study, we provide a straightforward experimental framework for drug toxicity assessment in renal organoids that may be used in early research stages to assist screen for potential adverse effects of compounds. |
| first_indexed | 2024-04-09T17:47:13Z |
| format | Article |
| id | doaj.art-7f4104345ea84b5891fe3e71127d251f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T17:47:13Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7f4104345ea84b5891fe3e71127d251f2023-04-16T11:14:30ZengNature PortfolioScientific Reports2045-23222023-04-0113111010.1038/s41598-023-33110-5A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoidsJasmin Dilz0Isabel Auge1Kathrin Groeneveld2Stefanie Reuter3Ralf Mrowka4Department of Internal Medicine III, Experimental Nephrology, Jena University HospitalDepartment of Internal Medicine III, Experimental Nephrology, Jena University HospitalDepartment of Internal Medicine III, Experimental Nephrology, Jena University HospitalThIMEDOP, Jena University HospitalDepartment of Internal Medicine III, Experimental Nephrology, Jena University HospitalAbstract Kidneys are complex organs, and reproducing their function and physiology in a laboratory setting remains difficult. During drug development, potential compounds may exhibit unexpected nephrotoxic effects, which imposes a significant financial burden on pharmaceutical companies. As a result, there is an ongoing need for more accurate model systems. The use of renal organoids to simulate responses to nephrotoxic insults has the potential to bridge the gap between preclinical drug efficacy studies in cell cultures and animal models, and the stages of clinical trials in humans. Here we established an accessible fluorescent whole-mount approach for nuclear and membrane staining to first provide an overview of the organoid histology. Furthermore, we investigated the potential of renal organoids to model responses to drug toxicity. For this purpose, organoids were treated with the chemotherapeutic agent doxorubicin for 48 h. When cell viability was assessed biochemically, the organoids demonstrated a significant, dose-dependent decline in response to the treatment. Confocal microscopy revealed visible tubular disintegration and a loss of cellular boundaries at high drug concentrations. This observation was further reinforced by a dose-dependent decrease of the nuclear area in the analyzed images. In contrast to other approaches, in this study, we provide a straightforward experimental framework for drug toxicity assessment in renal organoids that may be used in early research stages to assist screen for potential adverse effects of compounds.https://doi.org/10.1038/s41598-023-33110-5 |
| spellingShingle | Jasmin Dilz Isabel Auge Kathrin Groeneveld Stefanie Reuter Ralf Mrowka A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids Scientific Reports |
| title | A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids |
| title_full | A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids |
| title_fullStr | A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids |
| title_full_unstemmed | A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids |
| title_short | A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids |
| title_sort | proof of concept assay for quantitative and optical assessment of drug induced toxicity in renal organoids |
| url | https://doi.org/10.1038/s41598-023-33110-5 |
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