Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages
Abstract
:1. Introduction
2. Materials and Methods
2.1. MSC Culture and Production of Conditioned Medium (CM)
2.2. Ultra-Filtration of CM to Deplete Extracellular Vesicles
2.3. Thiol Measurement of CM
2.4. ciPTEC Culture and Cisplatin Treatment
2.5. ciPTEC Viability
2.6. ciPTEC Metabolic Activity
2.7. ciPTEC Migratory Capacity
2.8. ciPTEC Apoptosis
2.9. Nephrotoxicity PCR Array
2.10. Confirmatory RT-qPCR
2.11. Intracellular Reactive Oxygen Species Levels
2.12. Monocyte Isolation and Macrophage Culture
2.13. Macrophage Surface Marker Expression
2.14. Macrophage Phagocytosis
2.15. Indirect Co-Cultures of ciPTEC and Macrophages
2.16. Staining of ciPTECs on Transwell Membrane
2.17. Multiplex Assay to Quantify Secreted Factors in the Co-Culture System (Basolateral Side)
2.18. TNF-α Measurement in the Co-Culture System (Apical Side)
2.19. Statistical Analysis
3. Results
3.1. Cisplatin Decreases ciPTEC Viability, Metabolic Activity, and Migratory Capacity
3.1.1. ASC Secretome Attenuated Cisplatin-Induced Cell Toxicity and Promoted Migration of ciPTECs by Ameliorating Apoptosis, DNA Damage, and Oxidative Stress
3.1.2. Anti-Apoptotic Effect of CM Was Not Affected by EV Depletion but Related to Its Free Thiol Content
3.2. MSC-CM Promoted Macrophage Polarization towards the M2-like Phenotype
3.3. Macrophages Did Not Boost the Protective Effect of MSC-CM on ciPTECs
Despite Enhancing the Phagocytosis Capacity of Macrophages, CM Attenuated Macrophage Factor Secretion Triggered by ciPTECs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Rendra, E.; Uhlig, S.; Moskal, I.; Thielemann, C.; Klüter, H.; Bieback, K. Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells 2024, 13, 121. https://doi.org/10.3390/cells13020121
Rendra E, Uhlig S, Moskal I, Thielemann C, Klüter H, Bieback K. Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells. 2024; 13(2):121. https://doi.org/10.3390/cells13020121
Chicago/Turabian StyleRendra, Erika, Stefanie Uhlig, Isabell Moskal, Corinna Thielemann, Harald Klüter, and Karen Bieback. 2024. "Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages" Cells 13, no. 2: 121. https://doi.org/10.3390/cells13020121
APA StyleRendra, E., Uhlig, S., Moskal, I., Thielemann, C., Klüter, H., & Bieback, K. (2024). Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells, 13(2), 121. https://doi.org/10.3390/cells13020121