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Updated: Jun 27, 2026
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Time-course analysis of cisplatin induced AKI in preclinical models: implications for testing different sources of
Abantika Ganguly1, Shashank Chetty1, Rosita Primavera1
1Interventional Radiology Innovation at Stanford (IRIS), Department of Radiology, School of Medicine, Stanford University, 3155 Porter Drive, Palo Alto, CA, 94304, USA.
Background:
Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains.
Method:
In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI.
Result:
Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI.
Conclusion:
Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI.
Insights
This study developed a better preclinical model for cisplatin-induced kidney injury (AKI). Umbilical cord-derived mesenchymal stem cells (UC-MSCs) showed superior efficacy in reversing AKI compared to other MSC sources.
Area of Science:
- Nephrology
- Regenerative Medicine
- Pharmacology
Background:
- Drug-induced kidney injury, particularly from cisplatin, is a significant clinical concern.
- Current cytoprotective agents for cisplatin-induced acute kidney injury (AKI) have limitations, necessitating novel therapeutic strategies.
- Mesenchymal Stem Cells (MSCs) show promise for AKI treatment, but their clinical translation is hindered by source variability and challenges in preclinical modeling.
Purpose of the Study:
- To establish a standardized and robust preclinical model for cisplatin-induced AKI by analyzing time-course effects and inter-strain/gender differences in mice.
- To evaluate the therapeutic efficacy of different MSC sources in ameliorating cisplatin-induced AKI using the developed preclinical model.
- To identify potential biomarkers for assessing AKI severity and therapeutic response.
Main Methods:
- Conducted a time-course analysis of cisplatin's effects across various mouse strains, assessing gender-related differences.
- Utilized CXCL1 as a biomarker to compare the efficacy of different MSC sources (UC-MSCs, BM-MSCs, AD-MSCs) in reversing AKI.
- Developed a standardized preclinical model for evaluating AKI therapies.
Main Results:
- Mouse strain and cisplatin dosage significantly influenced AKI response, while gender did not show a significant bias.
- CXCL1 was identified as a key driver of cisplatin-induced inflammation and a reliable biomarker for AKI.
- Umbilical cord-derived MSCs (UC-MSCs) demonstrated superior anti-inflammatory effects and efficacy in ameliorating cisplatin-induced AKI compared to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (AD-MSCs).
Conclusions:
- An optimized preclinical model is crucial for accurately evaluating therapies for cisplatin-induced AKI.
- CXCL1 serves as a valuable biomarker for monitoring cisplatin-AKI.
- UC-MSCs represent a highly effective therapeutic option for mitigating cisplatin-induced kidney injury.
