The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Collection of the hAFS- and the hMSC-Conditioned Medium
2.3. In Vitro Experimental Outline
2.4. Analysis of Intracellular Dox Fluorescence and Evaluation of Cell Apoptosis In Vitro
2.5. Analysis of mNVCM Mitochondrial Organization and Their In Vitro Transmembrane Potential
2.6. Biochemical Profiling on mNVCM and mNVFib
2.6.1. Assessment of Oxygen Consumption Rate (OCR)
2.6.2. Assay for Fo-F1 ATP Synthase Activity
2.6.3. Evaluation of Oxidative Phosphorylation Efficiency
2.6.4. Glucose Consumption Assay
2.6.5. Lactate Release Assay
2.7. Preclinical Model of Dox-Induced Cardiomyopathy
2.7.1. In Vivo Model
2.7.2. Gene Expression Analysis
2.7.3. Evaluation of Aerobic Metabolism Alterations, Lipid Peroxidation, and Antioxidant Enzymatic Defenses
2.8. Statistical Analyses
3. Results
3.1. hAFS and hMSC Secretome Priming Preserves mNVCM from Unspecific Dox Uptake and from Dox-Induced Apoptosis
3.2. The Paracrine Potential of hAFS- and hMSC-CM Counteracts Dox-Induced Mitochondrial Dysfunction on mNVCM
3.3. Both hAFS- and hMSC-Secretome Preserve mNVFib from Dox-Induced Apotosis and Mitochondrial Impairment
3.4. hAFS- and hMSC-CM Protect Against DOX Cardiotoxicity In Vivo
4. Discussions
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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Villa, F.; Bruno, S.; Costa, A.; Li, M.; Russo, M.; Cimino, J.; Altieri, P.; Ruggeri, C.; Gorgun, C.; De Biasio, P.; et al. The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment. Cancers 2021, 13, 3729. https://doi.org/10.3390/cancers13153729
Villa F, Bruno S, Costa A, Li M, Russo M, Cimino J, Altieri P, Ruggeri C, Gorgun C, De Biasio P, et al. The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment. Cancers. 2021; 13(15):3729. https://doi.org/10.3390/cancers13153729
Chicago/Turabian StyleVilla, Federico, Silvia Bruno, Ambra Costa, Mingchuan Li, Michele Russo, James Cimino, Paola Altieri, Clarissa Ruggeri, Cansu Gorgun, Pierangela De Biasio, and et al. 2021. "The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment" Cancers 13, no. 15: 3729. https://doi.org/10.3390/cancers13153729